Coronavirus disease 2019 (COVID-19)

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

mild to moderate (non-severe) disease

1st line – consider home management or hospital admission

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1st line –

consider home management or hospital admission

Consider isolating patients with suspected or confirmed asymptomatic or mild to moderate disease.[85][656] For disease severity definitions, see Criteria.

Manage patients in a healthcare facility, in a community facility, or at home, according to guidance from your local public health authority.[85][656]

Home management can be considered in most patients, with telemedicine or remote visits as appropriate.
Manage patients at high risk of deterioration in a healthcare facility.

Be aware of any comorbidity-associated risk for clinical deterioration and severe disease

Monitor your patient with mild or moderate COVID-19 closely and consider the most appropriate setting of care and management.[1159] Take into account comorbidity-associated risk factors for developing severe disease including:[1160]

Age ≥50 years
Cardiac disease
Diabetes mellitus
Asthma
Chronic lung disease
Chronic kidney disease
Cerebrovascular disease
Chronic liver disease
Dementia
Mental disorders
Cancer
Immunosuppression
Obesity
Smoking
Possibly hypertension (evidence is inconsistent).

The World Health Organization (WHO) has a slightly different list, with a higher age limit of ≥60 years.[1159]

The WHO recommends you include pulse oximetry monitoring for your non-hospitalised patient with symptomatic non-severe COVID-19 with risk factors for severe disease, which include the comorbidities listed above.[1159]

Consider discussing your patient with the specialist team managing their long-term condition and/or referring to other healthcare professionals in the multidisciplinary team.

Multidisciplinary collaborative care is recommended for older people with COVID-19 to help ensure all aspects of care (including comorbidities) are adequately addressed.[1159]

Assess your patient’s level of frailty

Practical tip

Frailty is a distinctive health state related to the ageing process in which multiple body systems gradually lose their in-built reserves.[1161] See Frailty.

Ask about your patient’s capability 2 weeks BEFORE this acute episode (with input from carers if relevant).
Use the Clinical Frailty Scale (CFS) if your patient is aged ≥65 years old.[1162] Dalhousie University: Clinical Frailty Scale Opens in new window The National Institute for Health and Care Excellence recommends using the CFS when a person is admitted to hospital with COVID-19.[1163]
- This tool is a practical aid to identify frailty, but should not be relied on in isolation.
- A higher pre-hospital frailty score is associated with an increased risk of adverse outcomes including mortality in-hospital and up to12 months; readmission within 30 days; extended length of stay; discharge to a nursing home, residential care, hospital, or a high level of care; and functional decline.[1164] For patients with COVID-19 specifically, higher levels of frailty are reported in some but not all studies to have an increased mortality risk.[1159][1165][1166][1167]
If your patient scores 6 or higher, seek senior advice on appropriate local referral for holistic review, which should include a discussion about their treatment expectations and care goals.[1162]
Help to implement multidisciplinary care and tailor the management approach according to what the patient values most.[1168]

Implement local infection prevention and control procedures when managing patients. Advise patients in home isolation and household members to follow appropriate infection prevention and control measures:

WHO: home care for patients with suspected or confirmed COVID-19 and management of their contacts Opens in new window

Guidance on when to stop isolation varies widely across locations.

Isolation periods, if applicable, may depend on various factors including circulating SARS-CoV-2 variants and patient factors (e.g., immunocompetent/immunocompromised, asymptomatic/symptomatic, disease severity).
The World Health Organization recommends 10 days of isolation for symptomatic patients, and 5 days of isolation for asymptomatic patients (based on very low-certainty evidence). Rapid antigen testing may be used to reduce the period of isolation.[85]
Some countries now recommend isolation periods as short as 5 days to 7 days, and some no longer recommend isolation periods at all.
Consult your local public health guidance for more information.

Plus – set an escalation plan/consider ceiling of intervention

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Plus –

set an escalation plan/consider ceiling of intervention

Treatment recommended for ALL patients in selected patient group

In consultation with your patient (and their family or carers if applicable) agree an escalation plan as early as possible.[1163] This applies to all patients, but may be particularly relevant to patients living with frailty and/or with certain comorbidities, such as dementia, stroke, heart failure, COPD, and late-stage CKD (based on expert opinion).

An escalation plan should include:[1169]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of intervention (e.g., suitability for intubation or intensive care admission).
It should take account of advance care plans, including legally binding advance directives.[1159][1169]
It should be guided by your conversations with the patient about their individual wishes, including discussion to help them reach an informed decision about the likely benefit-risk balance of higher-intensity interventions.
Review the decision on CPR at intervals, and especially when an individual’s condition or expressed wishes change.[1170]

In some situations, a patient with dementia, other significant comorbidities, or learning disability (particularly if they are acutely unwell), will lack the mental capacity to make decisions for the escalation plan.

Assess and document mental capacity (the ability to make a specific decision at the time that the decision needs to be made).[1171] Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[1172] Assessments should follow the principles in the Act.[1172]
If your patient is assessed to lack mental capacity, consult with their next of kin to make ‘best interests’ decisions, bearing in mind what is known about the patient’s own previously expressed preferences.[1172] According to the 2005 Mental Capacity Act in England and Wales, if a patient is ‘unbefriended’ (i.e., has nobody to represent their best interests who is not paid to provide care) and a decision is not time-critical, you should seek an independent mental capacity advocate (IMAC) to perform this role.[1173] Check the appropriate legislation for your territory.

Plus – monitoring

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Plus –

monitoring

Treatment recommended for ALL patients in selected patient group

Closely monitor patients (particularly those with risk factors for severe illness) for signs and symptoms of disease progression. Counsel patients about signs and symptoms of deterioration or complications that require prompt urgent care (e.g., difficulty breathing, chest pain).[85]

Pulse oximetry monitoring at home is recommended in symptomatic patients with risk factors for progression to severe disease who are not hospitalised. Patient education and appropriate follow-up are required.[85]
If the patient is being managed in hospital, monitor patients closely for signs of clinical deterioration using medical early warning scores (e.g., National Early Warning Score 2 [NEWS2]), and respond immediately with appropriate supportive care interventions.[85]

Check baseline kidney function and monitor closely

Check baseline kidney function and monitor closely, especially if your patient has risk factors for AKI, including a history of CKD, diabetes, and/or heart failure.[1174]

Patients with CKD, diabetes, and/or heart failure who also have COVID-19 will be at increased risk of AKI, which may be related to, among other factors, fever, dehydration, and use of non-steroidal anti-inflammatory drugs.
- AKI in patients with COVID-19 may be common (although exact prevalence is uncertain). AKI is associated with increased mortality.[1163] See Complications.
Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[1159]

If your patient with COVID-19 is admitted to hospital, check kidney function on admission and ensure regular monitoring.[1159]

For patients with CKD, diabetes, and/or heart failure:[1174]
- Compare kidney function with last available results, and follow local protocol for detecting AKI
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion)
- Monitor for and respond to oliguria.

Plus – symptom management and supportive care

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Plus –

symptom management and supportive care

Treatment recommended for ALL patients in selected patient group

For the management of cough, advise patients to avoid lying on their back as this makes coughing ineffective, and follow your local guidelines for treating acute cough.[401]

Advise patients about adequate nutrition and appropriate rehydration.

Advise patients to drink fluids regularly to avoid dehydration. Fluid intake needs can be higher than usual because of fever. However, too much fluid can worsen oxygenation.[85][401]

Other supportive care measures include:

Advise patients to improve air circulation by opening a window or door[401]
Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate.[85]

Support your patient with known depression

Support patients treated at home who have pre-existing mental health conditions, such as depression. They may be experiencing increased emotional distress.

If appropriate, consider use of telemedicine to facilitate remote consultations.[1159][1175][1176]
Advise your patient on where to find locally relevant information and sources of support.

Consider treatment for olfactory dysfunction (e.g., olfactory training, intranasal corticosteroids) if it persists beyond 2 weeks.[659][660]

A Cochrane review found there is very limited evidence regarding the efficacy and harms of different interventions for preventing or treating persistent olfactory dysfunction following infection. The only evidence available is for intranasal corticosteroids (for prevention), and this is of very low certainty, so no conclusions could be drawn.[661][662]
A systematic review and meta-analysis found that there were no significant differences in the improvement of olfactory scores with either intranasal or oral corticosteroids plus olfactory training compared with olfactory training alone. Olfactory function was significantly improved after olfactory training.[663]

Consider – antipyretic/analgesic

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Consider –

antipyretic/analgesic

Additional treatment recommended for SOME patients in selected patient group

Paracetamol or ibuprofen are recommended.[85][401]

Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms. It is not recommended in pregnant women (especially in the third trimester) or children <6 months of age (age cut-offs vary by country).

NSAIDs in your patient with chronic kidney disease, heart failure, or asthma

Chronic kidney disease (CKD)

Avoid non-steroidal anti-inflammatory drugs (NSAIDs) in your patient with CKD.[1174]

Heart failure

Avoid NSAIDs as they increase the risk of worsening heart failure and hospitalisation with heart failure.[1177]

Asthma

NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[1178]

Primary options

paracetamol: children: consult local drug formulary for guidance on dose; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

paracetamol : children: consult local drug formulary for guidance on dose; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

paracetamol: children: consult local drug formulary for guidance on dose; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

ibuprofen: children: consult local drug formulary for guidance on dose; adults: 300-600 mg orally (immediate-release) every 6-8 hours when required, maximum 2400 mg/day

ibuprofen : children: consult local drug formulary for guidance on dose; adults: 300-600 mg orally (immediate-release) every 6-8 hours when required, maximum 2400 mg/day

ibuprofen: children: consult local drug formulary for guidance on dose; adults: 300-600 mg orally (immediate-release) every 6-8 hours when required, maximum 2400 mg/day

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

paracetamol

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

ibuprofen

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Plus – if your patient is not admitted to hospital, advise them on self-management of their diabetes

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Plus –

if your patient is not admitted to hospital, advise them on self-management of their diabetes

Treatment recommended for ALL patients in selected patient group

If your patient with diabetes is well enough to stay at home:

Advise them to follow sick-day rules from their individual healthcare professional or relevant national or regional professional diabetes organisation[1179][1180][1181][1182]
Despite limited evidence for this situation, diabetes self-management during illness with COVID-19 generally still follows the standard sick-day rules.[1183] Provide an individualised written management plan.

Advise your patient to seek urgent medical help if they are unable to keep any fluids down and cannot control their blood glucose.

Practical tip

Ensure your patient has adequate supplies of their diabetes medication and blood glucose monitoring equipment. If your patient has type 1 diabetes, ensure they also have a ketone meter and ketone strips.

Key general points for all patients with diabetes

Recommendations include to:[1180][1181]

Increase blood glucose monitoring
Drink sugar-free fluids to prevent dehydration, as this can contribute to quick progression to:
- Hyperglycaemia
- Diabetic ketoacidosis (DKA)
Maintain carbohydrate intake (this may be with sugary fluids if not able to eat or vomiting)
Rest and avoid strenuous exercise
Understand at what stage to seek further medical help, for example:
- Their blood glucose levels remain higher than usual
- They feel ill and are not improving
- They are not sure how to manage their condition themselves.

Practical tip

Be aware that blood glucose can increase during illness even when not eating. People who are ill with COVID-19 appear to have an even greater risk of developing hyperglycaemia with ketones, including those with type 2 diabetes (especially if they are taking a sodium-glucose cotransporter-2 (SGLT2) inhibitor).[1184]

People with type 1 diabetes

In addition to the general points above, make sure that during any acute illness patients with type 1 diabetes are aware of the need to:[1181]

Monitor their blood glucose every 2 to 4 hours
Test their blood for ketones and understand what these levels mean and what actions are required
Never stop insulin and adjust the dose if necessary
- Insulin dose increases are needed, even when not eating or vomiting, if blood glucose levels are >11 mmol/L (>198 mg/dL) (based on expert opinion)
- Consult local protocols for detailed step-by-step guidance on managing insulin dosing and frequency of blood glucose and ketone monitoring.

Most COVID-related consensus statements recommend SGLT2 inhibitors (e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) should be stopped during acute illness.[1185] These drugs are not approved for use in type 1 diabetes in the UK, but rarely patients may be taking these drugs on specialist advice.

If your patient usually takes this medication, advise them to test their blood for ketones even if their blood glucose is not elevated.[1184]
Patients on SGLT2 inhibitors are at risk of euglycaemic ketoacidosis.[1186] They should test their blood for ketones even after they have stopped their SGLT2 inhibitor.

People with type 2 diabetes

COVID-19 infection increases insulin resistance and reduces insulin secretion from the pancreatic beta cells. This can precipitate DKA in people with type 2 diabetes and even in people without previous diabetes.

In addition to the general points above, make sure patients with type 2 diabetes are aware of the need to:

Contact their family doctor to get advice on whether to adjust their diabetes medication.
- Patients with type 2 diabetes on insulin should monitor their blood glucose at least four times a day and usually continue their insulin although the dose may need adjusting (based on expert opinion).
- Patients who usually take a SGLT2 inhibitor for diabetes (e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) are recommended, in most COVID-19 consensus statements, to stop this medication during acute illness.[1185][1187] They are at risk of euglycaemic ketoacidosis with SGLT2 inhibitors and should check for blood ketones even once this medication is stopped.[1186] This may be something the patient is not familiar with doing, so organise this to be done urgently.
- Patients who usually take metformin are also advised, in most COVID-related consensus statements, to stop this medication during acute illness.[1185][1187] In this situation, metformin increases the risk of lactic acidosis.
- Be aware that withholding diabetes medications such as SGLT2 inhibitors or metformin may result in hyperglycaemia so patients should seek diabetes specialist advice on whether further action may be required (based on expert opinion).
- Patients who usually take gliclazide may need to reduce or omit a dose if they are not eating and drinking to avoid hypoglycaemia at night.[1187] On the other hand, during illness, some patients may develop hyperglycaemia so may need to temporarily increase their dose. Blood glucose monitoring is crucial to guide these decisions.

Sick-day rules from the UK NHS also recommend that patients stop glucagon-like peptide-1 (GLP-1) agonists (e.g., dulaglutide, exenatide, liraglutide, lixisenatide).[1187]

Practical tip

Check blood ketones as urinary ketone measurement may be unreliable.

Plus – review diabetes medication on admission to hospital (NEVER stop insulin in a person with type 1 diabetes)

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Plus –

review diabetes medication on admission to hospital (NEVER stop insulin in a person with type 1 diabetes)

Treatment recommended for ALL patients in selected patient group

This information is for managing your patient with diabetes and mild to moderate COVID-19 who has been admitted to hospital.

Practical tip

Contact your hospital’s diabetes specialist team for support in managing any patient with COVID-19 and diabetes.

Never stop basal insulin (long-acting/background insulin [e.g., glargine or degludec]) in a patient with type 1 diabetes who presents with an acute illness, including COVID-19.[1188]

Insulin deficiency (e.g., due to delayed or missed doses) will rapidly cause ketoacidosis.[1188]

Generally, any patient with type 2 diabetes who is on basal insulin should continue to receive it, but this may not always be the case so check with your senior and/or diabetes specialist team (based on expert opinion).

Be aware that COVID-19 appears to increase the risk of potentially life-threatening diabetes emergencies including:[1184][1189]

Hyperglycaemia with ketones
Diabetic ketoacidosis (DKA)
Hyperosmolar hyperglycaemic state (HHS)

This is the case in patients with COVID-19 with and without known diabetes.

Check the following on admission to hospital:[1184]

Blood glucose, in all patients
Blood ketones in all patients with diabetes (type 1 and type 2) and any patient who has a blood glucose on admission >12 mmol/L (>216 mg/dL)
HbA1c
- Admission HbA1c may give you an indication of your patient’s previous diabetes control and may influence your treatment on discharge (based on expert opinion).

Diagnose DKA in your patient with COVID-19 if:[1189]

Diabetes/hyperglycaemia: blood glucose ≥11.1 mmol/L (≥200 mg/dL) or prior history of diabetes
Ketosis: blood beta-hydroxybutyrate ≥3 mmol/L or urine ketone strip ≥2+
Metabolic Acidosis: blood pH <7.3 or bicarbonate <18 mmol/L.

Practical tip

In euglycaemic ketoacidosis, which may occur in people who have been taking sodium-glucose cotransporter-2 (SGLT2) inhibitors, the glucose level may not be significantly elevated.

The diagnosis of HHS is highly likely in the presence of:[1189]

Hyperglycaemia: blood glucose ≥33.3 mmol/L (≥600 mg/dL)
Hyperosmolarity: total serum osmolality ([(2 x Na) + glucose + urea]) >320 mOsm/kg or calculated effective serum osmolality ([(2 x Na) + glucose]) >300 mOsm/kg
AbSence of significant ketonaemia: blood beta-hydroxybutyrate <3 mmol/L or urine ketone strip <2+
Absence of acidosis: pH ≥7.3 and bicarbonate concentration ≥15 mmol/L.

Contact the diabetes specialist team and follow your local guidelines for management of DKA or HHS in patients with COVID-19, or if you suspect mixed DKA/HHS.

Diagnose hypoglycaemia if blood glucose <4 mmol/L (<72 mg/dL).

Follow your local protocol for management of hypoglycaemia.

Stop the following medication:[1184]

SGLT2 inhibitors prescribed for diabetes (e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin)
- SGLT2 inhibitors reduce blood glucose reabsorption in the kidneys (independently of insulin metabolism of glucose).[1190]
- They can mask underlying ketoacidosis as the patient may have a normal (or near normal) serum glucose level (euglycaemic ketoacidosis).[1190]
- If an SGLT2 inhibitor is continued during illness, for instance where it is being taken for its prognostic benefit for heart failure or to protect against progression of chronic kidney disease to kidney failure, be aware of the risk of euglycaemic ketoacidosiss, although the risk is low.[1191] Monitor ketone levels on a daily basis (based on expert opinion). It is still reasonable to withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness (when people may be at greater risk for ketosis).[1192] Seek expert advice.
- Check blood ketones as urinary ketone measurement may be unreliable.
- Restart SGLT2 inhibitors when ketone values are normal, your patient’s condition has stabilised, and they are eating and drinking.[1186]
Metformin
- Metformin is contraindicated in patients with significant renal impairment (estimated GFR <30 mL/minute/1.73 m²), or metabolic acidosis (including lactic acidosis or DKA).
- It is also contraindicated if the patient is at risk of lactic acidosis: for example, with acute kidney injury or tissue hypoxia (including acute cardiac or respiratory failure), dehydration, or if they are to be fasted for a prolonged period.
- Consider re-starting metformin depending on results of the patient’s blood lactate, kidney function, and arterial blood gases, as there is some evidence metformin may protect against progression to severe COVID-19.[1184]

The patient may need medication adjustment or to start insulin as a temporary measure if their usual anti-diabetes medication is stopped. Seek diabetes specialist team advice.

Follow local protocols regarding patients using wearable diabetes technology and seek diabetes specialist team advice.[1184]

Consider – antimicrobials

Consider – antiviral

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Consider –

antiviral

Additional treatment recommended for SOME patients in selected patient group

Consider an antiviral agent. Options include nirmatrelvir/ritonavir, molnupiravir, and remdesivir. Guideline recommendations vary.

The World Health Organization strongly recommends nirmatrelvir/ritonavir in patients with non-severe disease who are at high risk of hospitalisation, and conditionally recommends nirmatrelvir/ritonavir in patients with non-severe disease who are at moderate risk of hospitalisation. It suggests the use of molnupiravir or remdesivir in patients with non-severe disease who are at high risk of hospitalisation if nirmatrelvir/ritonavir is not available, but suggests against the use of these agents in patients who are at moderate risk of hospitalisation. Antiviral therapy is not recommended in patients who are at low risk of hospitalisation (most patients). For risk definitions, see 'World Health Organization: hospitalisation risk for patients with non-severe disease' in Criteria. Nirmatrelvir/ritonavir is a superior choice to other treatments for non-severe disease because it may have greater efficacy in preventing hospitalisation compared with the alternatives, has fewer concerns with respect to harms than does molnupiravir, and is easier to administer than intravenous remdesivir. However, it does have significant and complex drug-drug interactions.[402][654][655]
In the UK, the National Institute for Health and Care Excellence (NICE) recommends nirmatrelvir/ritonavir or molnupiravir for patients who do not need supplemental oxygen, and are thought to be at high risk of progression to severe disease. In addition to this, nirmatrelvir/ritonavir is also recommended in the following: people ≥70 years of age; people with a BMI ≥35 kg/m²; patients with diabetes or heart failure.[401][664]
In the US, the Infectious Diseases Society of America recommends nirmatrelvir/ritonavir or remdesivir as the preferred treatment options in patients with mild to moderate disease who are at high risk for progression to severe disease. Molnupiravir is recommended only in patients who have no other treatment options (i.e., nirmatrelvir/ritonavir or remdesivir).[398]

Treatment should be initiated as soon as possible after diagnosis, ideally within 5 days of symptom onset for nirmatrelvir/ritonavir or molnupiravir, or within 7 days of symptom onset for remdesivir.[398][401][402]

Logistical constraints may make it difficult to administer remdesivir in some outpatient settings as it requires administration via intravenous infusion.

Evidence for the use of antivirals in patients with non-severe disease is limited.

Nirmatrelvir/ritonavir was found to reduce the risk of hospitalisation or death by 89% (within 3 days of symptom onset) and 88% (within 5 days of symptom onset) compared with placebo in non-hospitalised high-risk adults in the phase 2/3 EPIC-HR trial.[667] However, the phase 2/3 EPIC-SR trial found that time to sustained alleviation of all signs and symptoms did not differ significantly between nirmatrelvir/ritonavir and placebo, regardless of vaccination status, in patients who were symptomatic (non-hospitalised) and at standard or high risk for severe disease.[668] Meta-analyses have found that nirmatrelvir/ritonavir reduced the risk of emergency department visits, hospitalisation, intensive care unit admission, oxygen requirement, and mortality. However, large-scale randomised controlled trials are required to confirm these findings.[669][670] One systematic review found that nirmatrelvir/ritonavir reduced the risk of mortality and hospitalisation in older patients (moderate-certainty evidence), but did not improve the outcomes of mortality and hospitalisation in patients <65 years of age (low-certainty evidence).[671] A Cochrane review found that nirmatrelvir/ritonavir may reduce the risk of all-cause mortality and hospital admission or death within 28 days in unvaccinated outpatients with previous infection who were at high risk with symptom onset within 5 days and infected with the Delta variant (low-certainty evidence from one trial). Very low-certainty evidence exists regarding the effects on all-cause mortality and viral clearance in unvaccinated inpatients with mild to moderate infection caused by the Omicron variant.[672]
Molnupiravir was found to reduce the risk of hospitalisation or death by 31% (absolute risk reduction from 9.7% to 6.8%) in the 29 days after use compared with placebo in non-hospitalised, unvaccinated, at-risk adults in the phase 3 MOVe-OUT trial.[673] However, the PANORAMIC trial found that molnupiravir did not reduce the risk of hospitalisation or death among high-risk vaccinated adults in the community compared with placebo, although it did reduce time to recovery.[674] Meta-analyses are conflicting. Some meta-analyses show no significant effect on reducing mortality or hospitalisation with molnupiravir.[675][676] However, others show that molnupiravir has a significant impact on reducing mortality and hospitalisation.[677][678] Emerging evidence suggests that use of molnupiravir may be contributing to the evolution of the SARS-CoV-2 virus, but further research is required.[679]
Remdesivir was found to reduce the risk of hospitalisation or death by 87% compared with placebo in non-hospitalised high-risk adults in a randomised, double-blind, placebo-controlled trial.[680]
When comparing nirmatrelvir/ritonavir and molnupiravir, nirmatrelvir/ritonavir demonstrated superiority to molnupiravir in terms of all-cause mortality and hospitalisation rate in one systematic review and meta-analysis. The incidence of adverse events was higher with nirmatrelvir/ritonavir, but no significant difference was observed between the two drugs in terms of adverse events that led to treatment discontinuation.[681]

Remdesivir and nirmatrelvir/ritonavir may be offered to pregnant women, if indicated. However, molnupiravir is not recommended for pregnant or breastfeeding women.[402]

A pregnancy test should be performed prior to initiation of molnupiravir because animal studies have shown reproductive toxicity and it may affect bone and cartilage growth. Contraception is recommended during molnupiravir treatment and for 4 days after the last dose in women of childbearing potential, and for at least 3 months after the last dose in men of reproductive potential who are sexually active with women of childbearing potential.
The World Health Organization recommends that pregnant or breastfeeding women may be offered nirmatrelvir/ritonavir as part of a fully informed shared decision-making process given the possible benefit and residual uncertainty regarding potential adverse effects.[402]
A case series of 47 pregnant women treated with nirmatrelvir/ritonavir found that treatment was well tolerated, although there was an unexpectedly high rate of caesarean deliveries. Further larger studies are needed to evaluate for complications in pregnant women and neonates.[770]

Remdesivir is associated with nephrotoxicity, hepatotoxicity, and hypersensitivity reactions.

Remdesivir may have little or no effect on acute kidney injury compared with placebo; however, the certainty of evidence is low.[771]
Transaminase elevations have been reported. Monitor liver function before starting treatment and during treatment as clinically appropriate. Consider discontinuing treatment if alanine aminotransferase (ALT) levels increase to ≥10 times the upper limit of normal. Discontinue treatment if ALT elevation is accompanied by signs or symptoms of liver inflammation.
Monitor prothrombin time before starting treatment and during treatment as clinically appropriate as increases in prothrombin time have been reported.
Administer in a setting where severe hypersensitivity reactions can be managed. Monitor patients during the infusion and observe for at least 1 hour after infusion. Bradycardia has been reported during the infusion and may persist past the initial infusion.[772][773]

Adverse effects with nirmatrelvir/ritonavir and molnupiravir are generally considered to be mild. However, there are limited safety data on these new medications, and all suspected adverse effects must be reported to your local pharmacovigilance programme.

Common adverse effects of nirmatrelvir/ritonavir include diarrhoea, dysgeusia, hypertension, and myalgia. Cases of abdominal pain, anaphylaxis, hypersensitivity reactions, toxic epidermal necrolysis, and Stevens-Johnson syndrome have been reported in postmarketing surveillance.[774] Use caution in patients with pre-existing liver diseases (ritonavir has been associated with elevated liver enzymes, hepatitis, and jaundice).
Common adverse effects of molnupiravir include diarrhoea, nausea, headache, and dizziness.
Cases of virological rebound (i.e., recurrent positive polymerase chain reaction result) and the recurrence of symptoms have been reported after antiviral treatment. However, it appears to be mild and self-limited. Virological rebound was more common in patients taking nirmtarelvir/ritonavir compared with untreated patients, but was also reported in patients taking molnupiravir.[665]

Nirmatrelvir/ritonavir has significant and complex drug-drug interactions, primarily due to the ritonavir component of the combination.

Carefully review the patient’s medication history before starting treatment.
Patients already on ritonavir-containing regimen for HIV or hepatitis C virus infection do not need to adjust the dose of their current antiviral regimen, and the dose of nirmatrelvir/ritonavir is unchanged for these patients (unless a dose adjustment is required based on the patient's renal function).
Recommendations for managing drug-drug interactions may differ for patients on extended courses of nirmatrelvir/ritonavir.
IDSA: management of drug interactions with nirmatrelvir/ritonavir Opens in new window

Take your patient’s medications and comorbidities into account when considering antiviral therapy

Comorbidities and risk of admission to hospital

Be aware that the World Health Organization (WHO) includes those with comorbidities of chronic disease, including diabetes, chronic cardiopulmonary disease, CKD, and others in the category of people at moderate risk of hospitalisation.[1193]

Consider nirmatrelvir/ritonavir in these patients if they have non-severe COVID-19.

The WHO includes those with immunodeficiency syndrome, those who have undergone solid organ transplant and are receiving immunosuppressants, and those with autoimmune illness receiving immunosuppressants in the category of people at high risk of hospitalisation.[1193]

Nirmatrelvir/ritonavir is recommended by the WHO in these patients if they have non-severe COVID-19.

The National Institute for Health and Care Excellence recommends nirmatrelvir/ritonavir in adults if they:[1163]

Do not need supplemental oxygen for COVID-19 and:
Have any of the following:
- Diabetes
- Heart failure
- An increased risk for progression to severe COVID-19
- Age ≥70 years
- A BMI of ≥35 kg/m².

Check your local national guideline as recommendations and risk categorisation vary.

Drug interactions

Be aware that nirmatrelvir/ritonavir has significant and complex drug-drug interactions.

Carefully review your patient’s medication history before starting treatment for risk of drug interactions. IDSA: management of drug interactions with nirmatrelvir/ritonavir Opens in new window
Monitor your patient closely during treatment.

Asthma or COPD

Before prescribing nirmatrelvir/ritonavir for your patient with COVID-19 and asthma or COPD, check for possible drug interactions.[1178]

Nirmatrelvir/ritonavir is a strong cytochrome P450 3A4 (CYP3A4) inhibitor. Concomitant use with medications that are metabolised by CYP34A may lead to greater exposure of the concomitant medication.
There is a potential increased risk of cardiotoxicity or other adverse effects if nirmatrelvir/ritonavir is used with salmeterol (and possibly vilanterol). These drugs are long-acting beta agonists.
There is a potential increased risk of Cushing’s syndrome and adrenal suppression when nirmatrelvir/ritonavir is used with inhaled corticosteroids (ICS). However, the risk is thought to be low with short-term use of nirmatrelvir/ritonavir in the context of COVID-19.
Concomitant prescribing of nirmatrelvir/ritonavir and ICS-salmeterol or ICS-vilanterol should generally be avoided if possible, due to the interaction with the LABA component.
Due to the risk of an exacerbation of asthma if the ICS-salmeterol or ICS-vilanterol is stopped during nirmatrelvir/ritonavir therapy, the Global Initiative for Asthma (GINA) advises considering an alternative antiviral or switching to an ICS alone or ICS-formoterol, and to continue for the duration of the nirmatrelvir/ritonavir therapy and for a further 5 days afterwards.[1178]
There is a risk of switching inhalers at a time of acute illness so the decision should be made on an individual case-by-case basis, balancing cardiotoxicity risk with severity of asthma/COPD (based on expert opinion). If it is not appropriate to switch inhalers, monitor the patient closely for signs of adverse effects during treatment.
If switching devices, remember to teach and check inhaler technique.[1178]

CKD

Nirmatrelvir/ritonavir is not recommended if your patient has an estimated glomerular filtration rate (eGFR) <30 mL/minute.[1194] Follow guidelines and prescribe a reduced dose if their eGFR is 30-59 mL/minute.

Primary options

nirmatrelvir and ritonavir: children ≥12 years of age and ≥40 kg body weight and adults with eGFR ≥60 mL/minute: 300 mg (nirmatrelvir)/100 mg (ritonavir) orally twice daily for 5 days; children ≥12 years of age and ≥40 kg body weight and adults with eGFR 30 to 59 mL/minute: 150 mg (nirmatrelvir)/100 mg (ritonavir) orally twice daily for 5 days

nirmatrelvir and ritonavir : children ≥12 years of age and ≥40 kg body weight and adults with eGFR ≥60 mL/minute: 300 mg (nirmatrelvir)/100 mg (ritonavir) orally twice daily for 5 days; children ≥12 years of age and ≥40 kg body weight and adults with eGFR 30 to 59 mL/minute: 150 mg (nirmatrelvir)/100 mg (ritonavir) orally twice daily for 5 days

Secondary options

remdesivir: children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 2 days

remdesivir : children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 2 days

remdesivir: children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 2 days

Remdesivir may be approved for use in children <12 years of age in some countries. Consult your local drug information source for more information. However, there is insufficient evidence to routinely recommend its use in children <12 years of age (treatment may be considered based on age and risk factors). No dose adjustment is required in patients with any degree of hepatic or renal impairment (including patients on dialysis).

molnupiravir: adults: 800 mg orally twice daily for 5 days

molnupiravir : adults: 800 mg orally twice daily for 5 days

molnupiravir: adults: 800 mg orally twice daily for 5 days

Primary options

nirmatrelvir and ritonavir : children ≥12 years of age and ≥40 kg body weight and adults with eGFR ≥60 mL/minute: 300 mg (nirmatrelvir)/100 mg (ritonavir) orally twice daily for 5 days; children ≥12 years of age and ≥40 kg body weight and adults with eGFR 30 to 59 mL/minute: 150 mg (nirmatrelvir)/100 mg (ritonavir) orally twice daily for 5 days

Secondary options

remdesivir: children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 2 days

remdesivir : children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 2 days

remdesivir: children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 2 days

molnupiravir: adults: 800 mg orally twice daily for 5 days

molnupiravir : adults: 800 mg orally twice daily for 5 days

molnupiravir: adults: 800 mg orally twice daily for 5 days

Back to drug information with added comorbidities

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

nirmatrelvir and ritonavir

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Secondary options

remdesivir

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

molnupiravir

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Consider – monoclonal antibody

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Consider –

monoclonal antibody

Additional treatment recommended for SOME patients in selected patient group

Consider a monoclonal antibody in patients who are at high risk of clinical progression. Guideline recommendations vary.

The World Health Organization strongly recommends against the use of sotrovimab and casirivimab/imdevimab for patients with non-severe disease, as there is evidence of a reduction in effectiveness against currently circulating variants of SARS-CoV-2 and their subvariants. The agency makes no recommendations for other monoclonal antibodies.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends offering sotrovimab as an option for treating patients ≥12 years of age and ≥40 kg body weight who do not need supplemental oxygen, who have an increased risk for progression to severe disease, and for whom nirmatrelvir/ritonavir is contraindicated or unsuitable.[401][664] Tixagevimab/cilgavimab is not recommended.[682]
In the US, the Infectious Diseases Society of America does not currently recommend the use of monoclonal antibodies for the treatment of COVID-19.[398]

Choice of monoclonal antibody depends on availability, as well as clinical and contextual factors including information about efficacy with different SARS-CoV-2 variants and subvariants.[401][402]

Options may include bebtelovimab, tixagevimab/cilgavimab, casirivimab/imdevimab, sotrovimab, bamlanivimab/etesevimab, and regdanvimab, depending on your location.
Check your local guidance for information about whether a particular monoclonal antibody is effective against current circulating SARS-CoV-2 variants and subvariants.
Logistical or supply constraints may make patient triage necessary. Treatment should be prioritised for patients who are at the highest risk of progressing to severe disease.

Evidence for the use of monoclonal antibodies in non-hospitalised patients is uncertain.

A Cochrane review found that the evidence is insufficient to draw meaningful conclusions about any specific monoclonal antibody, and the disease stage in which it should be used. Casirivimab/imdevimab decreases the risk of infection and development of clinical symptoms (high-certainty evidence). Bamlanivimab decreases the risk of infection (moderate-certainty evidence). These findings only apply to unvaccinated people, and are only applicable to variants prevailing during the study.[683]
A systematic review and meta-analysis of 27 randomised controlled trials found that monoclonal antibodies had limited effects on most of the outcomes in non-hospitalised patients with the certainty of evidence ranging from very low to moderate for most outcomes. Monoclonal antibodies reduced hospitalisation, but there were no effects on mortality.[684]

Monoclonal antibodies are generally administered by intravenous infusion.

Outpatient administration in specialised clinics is required, which may limit their feasibility.[402]
Treatment should be started as soon as possible and within 7 days of symptom onset.[401][402]

Hypersensitivity reactions, including infusion-related reactions and anaphylaxis, have been reported.

Administer in a setting where severe hypersensitivity reactions can be managed. Monitor patients during the infusion and observe for at least 1 hour after infusion.

Plus – continue your patient's inhalers as prescribed for asthma or COPD if appropriate

Back

Plus –

continue your patient's inhalers as prescribed for asthma or COPD if appropriate

Treatment recommended for ALL patients in selected patient group

Guidelines from several professional respiratory organisations agree that patients with asthma or COPD should be advised to continue to take their inhalers as prescribed (including inhaled corticosteroids), whether they do or do not also have COVID-19, if clinically appropriate.[1178][1195]

Patients with an acute medical condition can forget to tell you about their inhalers prescribed for COPD or asthma. Remember to check and prescribe if appropriate.

Before prescribing nirmatrelvir/ritonavir for your patient with COVID-19 and asthma or COPD, check for possible drug interactions.[1178]
- Nirmatrelvir/ritonavir is a strong cytochrome P450 3A4 (CYP3A4) inhibitor. Concomitant use with medications that are metabolised by CYP34A may lead to greater exposure of the concomitant medication.
- There is a potential increased risk of cardiotoxicity or other adverse effects if nirmatrelvir/ritonavir is used with salmeterol (and possibly vilanterol). These drugs are long-acting beta agonists.
- There is a potential increased risk of Cushing’s syndrome and adrenal suppression when nirmatrelvir/ritonavir is used with inhaled corticosteroids (ICS). However, the risk is thought to be low with short-term use of nirmatrelvir/ritonavir in the context of COVID-19.
- Concomitant prescribing of nirmatrelvir/ritonavir and ICS-salmeterol or ICS-vilanterol should generally be avoided if possible, due to the interaction with the LABA component.
- Due to the risk of an exacerbation of asthma if the ICS-salmeterol or ICS-vilanterol is stopped during nirmatrelvir/ritonavir therapy, the Global Initiative for Asthma (GINA) advises considering an alternative antiviral or switching to an ICS alone or ICS-formoterol, and to continue for the duration of the nirmatrelvir/ritonavir therapy and for a further 5 days afterwards.[1178]
- There is a risk of switching inhalers at a time of acute illness so the decision should be made on an individual case-by-case basis, balancing cardiotoxicity risk with severity of asthma/COPD (based on expert opinion). If it is not appropriate to switch inhalers, monitor the patient closely for signs of adverse effects during treatment.
- If switching devices, remember to teach and check inhaler technique.[1178]
Many inhalers contain a combination of medications, so ensure no dual prescribing.
Patients with COPD or asthma who develop acute kidney injury with an estimated GFR <50 mL/minute/1.73 m² may need to temporarily stop their usual inhaled long-acting muscarinic antagonist, depending on which specific drug is used.
- Check local formulary or seek pharmacist advice.

Other prescribed medication

Patients with severe asthma or COPD who take oral corticosteroids as regular prescribed maintenance therapy should also continue to take these at the lowest dose possible, as their condition may deteriorate if these are stopped.[1178][1195]
Patients who take biological therapy for severe asthma should continue to take this treatment, unless specifically advised not to do so.[1178]

Plus – if your patient is not admitted to hospital, ensure plans are in place in case of any asthma exacerbation

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Plus –

if your patient is not admitted to hospital, ensure plans are in place in case of any asthma exacerbation

Treatment recommended for ALL patients in selected patient group

If your patient with COVID-19 is being managed at home, advise them to follow their personalised action plan and to continue taking their usual asthma medications including biological therapy or oral corticosteroids.[1178]

Poorly controlled asthma (such as recent need for oral corticosteroids) increases the risk of hospitalisation for severe COVID-19.[1178]

Advise your patient to seek medical advice if they think they are having an exacerbation of asthma.[1178]

Follow established guidelines if asthma worsens, and consider hospital admission.
Start oral corticosteroids as indicated for asthma exacerbations.[1178][1196]

Nebulisers should be avoided, if possible, to reduce risk of transmitting infection. A pressurised metered dose inhaler with a spacer is preferred.[1178]

Plus – if your patient is not admitted to hospital, ensure plans are in place to manage any COPD exacerbation

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Plus –

if your patient is not admitted to hospital, ensure plans are in place to manage any COPD exacerbation

Treatment recommended for ALL patients in selected patient group

If an exacerbation of COPD is suspected in a patient with mild to moderate COVID-19 and pre-existing COPD, follow the patient’s personalised action plan. If your patient is at home, ensure they know to seek medical advice.

Follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[1195] Seek specialist advice and consider hospital admission.
- The standard recommended length of course for oral corticosteroids if prescribed for exacerbation of COPD is 5 days.[1195][1197]
Differentiate from other conditions, such as acute coronary syndrome, acute heart failure, and pneumonia, as well as from complications of COVID-19.[1195]
See Acute exacerbation of COPD.

Plus – weigh up risks versus benefits of prescribed antihypertensive medication

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Plus –

weigh up risks versus benefits of prescribed antihypertensive medication

Treatment recommended for ALL patients in selected patient group

The World Health Organization recommends that antihypertensive drugs should not routinely be stopped in patients with COVID-19, but may need adjusting depending on the patient’s clinical condition, particularly their blood pressure and kidney function.[1159]

Despite initial concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, high-certainty evidence has found that the use of these drugs is not associated with severe disease or poor outcomes.[1198][1199][1200]

The UK Kidney Association and the British Cardiovascular Society recommend following standard current guidance on the management of any intercurrent acute illness when weighing up the benefit versus risk of stopping renin-angiotensin-aldosterone system (RAAS) inhibitors in the context of suspected COVID-19.[1201][1202][1203] Recommendations include to:

Do an individual clinical assessment
Consider the original indication for any RAAS inhibitors (ACE inhibitors, angiotensin-II receptor antagonists, mineralocorticoid receptor/aldosterone antagonists) and degree of prognostic benefit
If medication is temporarily withheld, consider when to re-introduce again once health improves.

If not already done, consider calculating a frailty score (e.g., using the Clinical Frailty Scale) as patients with higher frailty scores may be more likely to experience medication-related harm when acutely ill (based on expert opinion). Dalhousie University: Clinical Frailty Scale Opens in new window

Patients who self-manage their heart failure in a community setting may wish to reduce their dose of diuretics during an intercurrent illness that may result in dehydration (based on expert opinion).

Seek advice from the patient’s cardiology or nephrology team if they have complex conditions (e.g., on renal replacement therapy or immunosuppressive therapy).

Plus – monitor comorbidities during hospital stay

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Plus –

monitor comorbidities during hospital stay

– baseline neurological assessment

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–

baseline neurological assessment

Treatment recommended for ALL patients in selected patient group

Do a baseline neurological assessment at the earliest appropriate opportunity in patients who have a history of stroke and are admitted to hospital with an acute medical condition, including COVID-19.

Reported neurological manifestations associated with COVID-19 include acute ischaemic and haemorrhagic stroke.[1159]
Generally a patient with an acute condition (e.g., an infection and illness-related hypotension) is at increased risk of stroke.[1204][1205][1206] This risk is even higher in anyone with a history of stroke.
Compare the baseline assessment with the patient’s known pre-COVID-19 neurological status. This could be done by asking the patient, family, and carers about the patient’s functional ability before becoming ill (based on expert opinion).
- This should reduce the risk of misattributing neurological signs on admission to the previous diagnosis of stroke.
If there is a change in neurological status during admission, repeat the neurological assessment in case of a new stroke.
Following assessment, ensure the right level of patient supervision (e.g., relating to the risk of confusion at night and the risk of falls associated with frailty).
- A patient with a history of stroke is at increased risk of falling and injury.[1207]

The World Health Organization recommends that patients in hospital with COVID-19 are monitored closely for signs of clinical deterioration, including for signs or symptoms of stroke.[1159]

– baseline cognitive and delirium assessments with collateral history

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–

baseline cognitive and delirium assessments with collateral history

Treatment recommended for ALL patients in selected patient group

Do a baseline cognitive assessment at the earliest opportunity in any patient admitted to hospital with an acute condition and with dementia or suspected frailty. Take a collateral history from family, friends, or carers.[1208]

Use a validated scoring system that is feasible in the acute setting, such as the abbreviated mental test score/10 (AMTS/10).[1208][1209] British Geriatrics Society: Abbreviated Mental Test Score. 2018 Opens in new window
- Be aware that, while highly specific, the AMTS may underestimate the degree of cognitive impairment and more detailed assessment may be required in selected patients.[1210]
The collateral history establishes whether the patient’s cognition is stable, or if any decline in cognition and function has been gradual or acute.
A standardised cognitive assessment score is useful for monitoring for any clinical improvement, and for establishing needs on discharge. This score is often best interpreted alongside a functional assessment, usually performed by a trained occupational therapist.
Although the score may not represent the person's usual baseline for cognition due to the impact of the acute condition and its treatment, it is still good practice to record and repeat it when the person has recovered (based on expert opinion).

Delirium

Delirium is an acute deterioration in mental functioning arising over hours or days that is triggered mainly by acute medical illness, surgery, trauma, or drugs.[1211] Your patient may also have an altered level of arousal and be experiencing hallucinations or delusions.[1211] See Assessment of delirium.

Use a screening tool to detect probable delirium, such as:
- The 4AT.[1211][1212][1213][1214]
  - More information on calculating the 4AT has been produced by the Scottish Intercollegiate Guidelines Network. 4AT calculator Opens in new window
- The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC) if your patient is in a critical care setting or in the recovery room after surgery.[1212]
  - Recommended by the UK National Institute for Health and Care Excellence (NICE) as specifically designed for these settings, but training is needed, which may limit implementation.[1212]

Assess for delirium whenever a patient with dementia presents with acute illness.[1212] Also assess for delirium in your patient with frailty.[1215] Your patient with COVID-19 may present with delirium and have no respiratory symptoms.[1159] The World Health Organization recommends that patients with COVID-19 are assessed for delirium using standardised protocols.[1159]

People living with dementia are at increased risk of delirium when they are admitted to hospital and throughout their admission.[1211][1216]
Frailty increases the risk of delirium threefold during hospital admission.[1215]

Consider the following actions as part of multicomponent care to reduce the risk of delirium during a hospital admission in people with dementia or frailty with any acute condition:[1211][1217]

Help with orientation; make sure patients have their own glasses and/or hearing aids
Get patients mobilised as soon as possible
Control pain adequately
Identify and treat superadded infections promptly
Keep well hydrated and help patients to eat adequately
Monitor and maintain regular bowel and bladder function
Use supplementary oxygen according to guideline recommendations.

Arrange a medication review with an experienced healthcare professional:[1211]

Calculate the anticholinergic burden (ACB) score.[1218]
A score of 3 or more may increase the risk of delirium within 24-48 hours of admission.[1219]
Consider discontinuing or substituting anticholinergic drugs where possible, but be aware of the need to taper some medications to avoid withdrawal side effects such as nausea and sweating.[1220]

Challenges specifically related to COVID-19 include:[1217]

The need for isolation, which may exacerbate delirium in some patients
The ability to regularly monitor patients for delirium, which may be affected by staffing and time resources available.

More info: Investigations

Initial investigations for a patient with delirium

If a patient has delirium, check for and treat life-threatening causes:[1211]

Hypoxia
Low blood glucose
Hypotension
Drug intoxication or withdrawal, including alcohol withdrawal.

Other investigations include (based on expert opinion):

Full blood count, electrolytes, renal function, thyroid function tests, liver function tests, calcium, glucose, CRP, folate, and vitamin B12
Blood cultures (if bacteraemia is suspected)
Urine culture
Chest x-ray.

Advanced non-routine investigations such as CT head may be needed, depending on specific clinical findings. Discuss with your senior.[1211]

Check for and treat any reversible causes of delirium.[1212] These include:

Pain
Infection
Poor nutrition
Constipation
Dehydration
Medications
- Ask about recently prescribed medications, especially opioid analgesics, anxiolytics, sedatives, antipsychotics, or medicines with strong anticholinergic properties
- Consider calculating a total anticholinergic burden score
Environment (including immobility, poor sleep, sensory impairment such as ear wax or loss of glasses).

The mnemonic PINCH ME may be helpful as an aide memoire for the underlying causes of delirium superimposed on dementia.[1221]

Management of a patient with delirium in hospital and long-term care

Manage patients with delirium initially, if possible with non-pharmacological treatment as recommended in management of delirium in a non-COVID-19 context.[1159][1212]

Reduce disorientation by providing a well-lit room, with a clock and calendar visible (e.g., on the wall).
Encourage and facilitate family, friends, and carers to visit the patient, within restrictions of your visiting policy as determined by current levels of community COVID-19 transmission.
Use verbal and non-verbal techniques to de-escalate conflict and distress.

Where non-pharmacological treatments are ineffective, and the patient is distressed or considered a risk to themselves or others, short-term (often only 1-2 days is required) antipsychotic or sedative drugs may be considered, but only as a last resort. Any new antipsychotic prescribed for this purpose must be regularly reviewed, and discontinued as soon as practical (based on expert opinion).

The British Geriatrics Society has stated that in the context of management of a patient with COVID-19, it may be necessary to progress to pharmacological management earlier than would normally be considered in other circumstances because the risk of transmission of infection causing harm to others may be considered to be greater than potential harm to the individual.[1217]
The UK NICE guideline on delirium recommends short-term use of haloperidol (usually for less than 1 week), but it is not suitable in all patients and must never be used in patients with Parkinson’s disease or in patients with dementia with Lewy bodies.[1212]
- Take particular care to closely monitor and regularly review older people with frailty when prescribing haloperidol for acute delirium. They are particularly at risk of adverse neurological and cardiac effects of this drug.[1222]
  - A baseline ECG and correction of electrolyte abnormalities is recommended before starting haloperidol.
  - Prescribe at the lowest dose and for the shortest length of time possible.
  - During treatment, cardiac and electrolyte monitoring is recommended, as is monitoring for extrapyramidal adverse effects.
The evidence on the efficacy of antipsychotics for delirium is inconclusive, and hospital protocols may vary.[1211] Follow your local hospital protocol for choice of medication.
Always start at the lowest dose for antipsychotic drugs and titrate carefully according to symptoms.[1159][1212] Only ever use oral or intramuscular medication (never intravenous) for this purpose (based on expert opinion).

Provide the family/carers with information so they understand what is happening and how they can work together with the clinical team to help the patient get back to their usual self.[1211] Provide locally available information resources.[1217]

Evidence: Risks and safe withdrawal of antipsychotics in older people

Antipsychotics are associated with increased mortality in people with dementia.

Short-term antipsychotics may sometimes be needed in people with dementia without delirium to enable safe care. However, antipsychotics have various adverse effects in older people and are associated with an increased risk of death in people with dementia.

A Cochrane review found very low-certainty evidence that typical antipsychotics such as haloperidol improve agitation, and may improve psychosis slightly in people with Alzheimer’s disease and vascular dementia. Atypical antipsychotics probably reduce agitation. Both types increase the risk of somnolence and extrapyramidal symptoms.[1223]
A network meta-analysis found that people who take atypical antipsychotics for behavioural and psychological symptoms of dementia may have a small improvement in behavioural and psychological symptoms but have increased safety risks including cerebrovascular adverse events compared with those taking placebo.[1224]
Contrary to popular belief, long-term antipsychotic prescriptions can be safely withdrawn in most people with dementia once behaviour has settled.[1225]

If delirium is not responding to initial treatment within 48 hours, refer to a healthcare professional trained and skilled at diagnosing delirium to confirm the diagnosis and treatment plan (based on expert opinion).

Document the diagnosis of delirium clearly.[1211][1212]

– ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

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–

ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

Treatment recommended for ALL patients in selected patient group

Monitor for acute worsening of respiratory symptoms and be aware that this may suggest a patient with comorbid asthma is having an acute exacerbation of their asthma.

Seek senior advice.
Follow standard guideline recommendations on assessing severity and managing an acute exacerbation of asthma in adults, even if COVID-19 is suspected as the trigger.[1196]
- See Acute asthma exacerbation in adults.
- Avoid using a nebuliser where possible. Consider whether it may be clinically appropriate to use a metered-dose inhaler delivered via a spacer device with a mouthpiece or tightly fitted face mask as an alternative delivery mechanism to a nebuliser.[1178] Follow your local protocols.
Start oral corticosteroids as clinically indicated for asthma exacerbations.[1178][1196]
Consider temporarily stopping any long-acting muscarinic antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a short-acting muscarinic antagonist (e.g., ipratropium) (based on expert opinion).
- This is due to concern over possible additive anticholinergic adverse effects.
- Ensure to re-prescribe the LAMA once the nebuliser treatment has been stopped.

– ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

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–

ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

Treatment recommended for ALL patients in selected patient group

If an exacerbation of COPD is suspected in a patient with COVID-19 and pre-existing COPD:

Seek senior or specialist advice.
Differentiate from other conditions, such as acute coronary syndrome, acute heart failure, and pneumonia, as well as from complications of COVID-19.[1195]
Follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[1195] See Acute exacerbation of COPD.
Consider using pressurised metered-dose inhalers, dry powder inhalers, or soft mist inhalers for drug delivery instead of nebulisers in non-critically ill patients not receiving ventilatory support.[1195] Follow your local guidance and protocols.
The Global Initiative for Chronic Obstructive Disease recommends continuing inhaled long-acting bronchodilators during an exacerbation, or starting them as soon as possible before discharge from hospital.[1195] This is an individualised clinical decision due to limited evidence.
Consider temporarily stoping any long-acting muscarinic antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a short-acting muscarinic antagonist (e.g., ipratropium) (based on expert opinion).
- This is due to concern over possible additive anticholinergic adverse effects.
- Ensure the LAMA is re-prescribed once the nebuliser treatment has been stopped.

– monitor and manage blood glucose during the hospital admission

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–

monitor and manage blood glucose during the hospital admission

Treatment recommended for ALL patients in selected patient group

Monitor blood glucose levels at least four times a day (every 4-6 hours or, if eating, pre-meal and before bedtime) in any acutely ill patient with diabetes mellitus.[1226]

Follow your local protocol on blood glucose monitoring for inpatients with COVID-19 who have diabetes.

The UK-based National Inpatient Diabetes COVID-19 Response Group recommends a target blood glucose of between 6 and 10 mmol/L (108-180 mg/dL), with up to 12 mmol/L (216 mg/dL) being acceptable for patients in hospital with COVID-19.[1227]

Hyperglycaemia during the ongoing hospital admission

Act promptly to treat hyperglycaemia to avoid diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS), which are medical emergencies.

Follow your local hospital protocol if your patient’s capillary blood glucose is ≥12 mmol/L (≥216 mg/dL).
- COVID-19 guidance generally emphasises the importance of managing hyperglycaemia.[1185]
- Exclude DKA or HHS, both of which require specific urgent management.
- Consider other conditions associated with hyperglycaemia, such as sepsis.[1184]
Be aware that the following medications may be associated with hyperglycaemia and may need to be reviewed:[1228]
- Corticosteroids (e.g., dexamethasone)
- Some beta-blockers (e.g., propranolol, atenolol)
- Thiazide diuretics (e.g., hydrochlorothiazide)
- Some second-generation antipsychotics (e.g., olanzapine, clozapine)
- Certain fluoroquinolone antibiotics (e.g., ciprofloxacin)
- Calcineurin inhibitors (e.g., ciclosporin, tacrolimus)
- Protease inhibitors (e.g., ritonavir).
If your patient does not have DKA/HHS but has a blood glucose above 12 mmol/L (216 mg/dL), follow your local protocols on management of hyperglycaemia in patients with COVID-19.[1227]
- Be aware that patients with type 2 diabetes in ICU may have significant degrees of insulin resistance. Seek support from your diabetes specialist inpatient team in these circumstances.[1227]

Practical tip

Ask for expert advice from the inpatient diabetes team.

Hypoglycaemia during the ongoing hospital admission

Monitor blood glucose and adjust medication in response to illness and hospital meal times, to reduce the risk of hypoglycaemic episodes.

Approximately 1 in 5 inpatients with diabetes in England and Wales were found to have had a hypoglycaemic episode during their hospital stay.[1229]

Causes of hypoglycaemia include:[1230]

Recovery from an acute illness
- Patients recovering from COVID-19 may have a rapid change in insulin requirements, so monitor and adjust insulin regimens carefully[1227]
Accidental interruptions to patient feeding, which may occur especially when patients with COVID-19 are nursed in the prone position[1184]
Reducing doses of corticosteroids, particularly dexamethasone in patients with COVID-19[1227]
Insulin or oral hypoglycaemic medication error
Wrong timing of insulin in relation to meals
Patients eating less but taking the same amount of diabetes medication
No bedtime snacks
Reduced appetite or vomiting.

Be aware that hypoglycaemia as an adverse effect of sulfonylurea medication (e.g., glibenclamide, gliclazide, glimepiride, glipizide) is more likely if meals are skipped or doses are excessive.

In the acute hospital setting, meal times may be interrupted or may not always be at exactly the same time each day.
- Give sulfonylurea medication before or with food. Check local drug formulary for more specific guidance on timing of dose in relation to food for specific sulfonylurea.
- Never give sulfonylurea medication at bedtime and, if the patient is taking a dose with their evening meal, consider reducing the evening dose to reduce the risk of nocturnal hypoglycaemia (based on expert opinion).

Practical tip

Bedtime snacks can reduce the risk of early morning hypoglycaemia.[1229]

Consider intervening if the blood glucose falls below 6 mmol/L (108 mg/dL) (‘looming/impending’ hypoglycaemia) if on insulin or on sulfonylureas.

These patients are at high risk of progressing to hypoglycaemia.
Give carbohydrates as recommended in the hypoglycaemia guideline and follow your local protocol.[1230]

Treat hypoglycaemia actively if the blood glucose falls below 4 mmol/L (72 mg/dL).[1230] Follow hospital protocol or the Joint British Diabetes Societies for Inpatient Care (JBDS-IP) management of hypoglycaemia algorithm.[1230] The JBDS-IP guidelines also recommend that you:[1230]

Retest blood glucose at 10 to 15 minutes to determine response to treatment
Never stop the next scheduled dose of insulin if the hypoglycaemia has been corrected. This can cause rebound hyperglycaemia and DKA in people with type 1 diabetes.
- Seek diabetes inpatient specialist team advice on whether a review of your patient’s insulin regimen is needed.

Follow local protocols and guidance on self-monitoring of blood glucose by patients in hospital.

These may have been adapted in the context of patients with COVID-19. For instance, some hospitals in the US have been utilising ‘virtual’ formats, including expanding self-management protocols, to reduce need for personal protective equipment, where it is safe to do so.[1185]

– check your patient’s feet

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check your patient’s feet

Treatment recommended for ALL patients in selected patient group

Check the feet of any adult with diabetes on admission to hospital and whenever they seem more ill.[1231] This recommendation applies to adults with diabetes admitted to hospital with COVID-19.[1184]

A foot check is needed to detect new ulceration or infection, which may be unnoticed by the patient.

Inspect the foot for lesions and examine for loss of protective sensation.

Follow your local guidelines, but a quick simple test is the Ipswich Touch Test©️, which involves lightly touching/resting the tip of the index finger for 1 to 2 seconds on the tips of the first, third, and fifth toes.[1232]
- If your patient is unable to feel at two or more of these six sites, they have reduced protective sensation.
If your patient has reduced sensation, they are at high risk of pressure ulceration. Inform the nursing staff and provide pressure relieving devices.

A daily heel check for signs of pressure trauma should be done by nursing or healthcare assistant staff.

There is a debate about whether compression stockings should or should not be used in people with diabetes – do not use them if there is vascular disease.

– mental state examination

– review current treatment for depression

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review current treatment for depression

Treatment recommended for ALL patients in selected patient group

Ask your patient which medications they are taking for their mental health. Alternatively, review their primary care records for relevant information (if available).

Drug-drug interactions and their associated adverse effects of particular relevance to patients with COVID-19 include sedation, cardiotoxicity (QT prolongation), and respiratory depression.[1159]

Consider that antidepressants may be used in the treatment of conditions other than depression, and drugs other than antidepressants may be used to treat depression.

Prescribe the patient’s usual antidepressant medication, unless there are good reasons not to (based on expert opinion).

If antidepressants are stopped abruptly, the patient may develop discontinuation symptoms.[1235]
The severity of symptoms of discontinuation may vary, but it may be unpleasant and may complicate the management of the acute medical condition.[1235][1236]

When reviewing current medication, look out for:

Current and previous adverse effects
Recent changes in dose
Recent switches from a different class of medication
Pharmacological nuances of specific depression subtypes (e.g., it is likely that patients suffering from psychotic depression would be co-prescribed an antipsychotic)
Augmenting strategies that may be in use when treating resistant depression (e.g., lithium or quetiapine augmentation of a selective serotonin-reuptake inhibitor [SSRI]).

Consider drug-drug interactions.

Antidepressant medications may cause pharmacokinetic (by inhibiting the CYP450 pathway) and pharmacodynamic interactions with medications used for other conditions.[1237][1238] Consider this issue for all medications prescribed in patients with COVID-19 as well as any experimental therapies (see the Emerging section).

Consider psychiatric complications when prescribing non-psychotropic drugs.

Take particular care when prescribing corticosteroids, anticonvulsants, and antiparkinsonian medication.

Consider adverse effects, which may include the following.[1238]

QT prolongation, arrhythmias, increased heart rate, or postural hypotension with tricyclic antidepressants. Check ECG, especially in people at risk of arrhythmias.
Hyponatraemia, caused by antidepressants, especially SSRIs, and compounded by other co-prescribed drugs (e.g., diuretics). Check your patient’s serum electrolytes.
Serotonin syndrome (altered mental state, agitation, tremor, hyper-reflexia, clonus, muscle rigidity, diaphoresis, tachycardia, increased bowel sounds, temperature >38℃), especially with polypharmacy and/or overdose of a serotonergic agent.[1239][1240] See Serotonin syndrome.
- Be particularly aware of increased risk of serotonin syndrome in patients with end-stage renal disease on SSRIs. Treating depression in patients with renal impairment requires a multidisciplinary approach and demands extra caution.
Hepatotoxicity. Adjust doses of antidepressants in patients with hepatic impairment if necessary and avoid drugs that are known to be hepatotoxic.
Gastrointestinal bleeding. SSRIs are associated with an increased risk of gastrointestinal bleeding.[1238] Risk is particularly increased when co-prescribed with aspirin, non-steroidal anti-inflammatory drugs, or oral anticoagulants.[1241][1242] Try to avoid this combination of drugs.[1238] Monitor closely and consider gastroprotection with proton-pump inhibitors if SSRI use cannot be avoided.[1238]

This list of adverse effects and drug-drug interactions is not exhaustive – consult local formulary for further information. Consult your liaison psychiatry colleagues and/or a pharmacist for advice.

Ask your patient about non-pharmacological treatments for their depression and check the current level of support in the community.

This may include other health professionals involved in their care, charities, family and social networks, and psychological therapy.

Practical tip

Be aware that smoking cessation or switching from tobacco smoking to alternatives (including nicotine replacement therapy) may result in a change to the plasma concentration of any psychotropic medication the patient may be taking (e.g., for depression). This is because nicotine replacement therapy does not impact hepatic enzyme activity like tobacco smoking.[1243][1244][1245] Seek advice on whether any adjustment to the dose of psychotropic medication is appropriate.

– consider referral to the liaison psychiatry team

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consider referral to the liaison psychiatry team

Treatment recommended for ALL patients in selected patient group

Consider a referral to the liaison psychiatry team/service for any patient with established or suspected depression who is admitted to hospital with an acute condition.[1246][1247]

Referral may not be required if there are no concerns that depression and/or its management (e.g., medication) may be impacting on the acute condition (based on expert opinion).
Follow your local protocols/referral pathways in your hospital.
COVID-19 is associated with psychiatric and neurological manifestations including depression.[1159]

Evidence: Depression and adherence to treatment post-discharge

Comorbid depression is linked to poor adherence with recommended physical health treatments, from medication to rehabilitation.[1248]

This may lead to worse clinical outcomes, including higher readmission risk.[1249][1250][1251]
Most importantly, affective symptoms including depression have been linked with excess mortality, though a causal link remains to be proven.[1252][1253]

– manage nicotine dependence and support current smokers to stop smoking

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manage nicotine dependence and support current smokers to stop smoking

Treatment recommended for ALL patients in selected patient group

If your patient is a current smoker, provide access to stop-smoking support.[1254] Appropriate timing for this is dependent on the clinical situation. In general, the National Institute for Health and Care Excellence recommends this should be provided immediately or within 24 hours.[1254]

Evidence suggests there is an association with increased severity of COVID-19 and risk of death in hospitalised patients who smoke tobacco.

In light of this, in addition to the well-recognised harms, the World Health Organization recommends smoking cessation using evidence-based methods.[1255]

Offer nicotine replacement therapy (NRT) and other smoking cessation pharmacotherapies for all inpatients who smoke if there are no contraindications.[1254]

Advise that:[1254]

Nicotine is highly addictive but is not the cause of smoking-related harms
NRT prevents rapid withdrawal during admission, which can be distressing and uncomfortable
There are several highly effective treatment options that offer the best chance of stopping smoking when combined with specialist support.

NRT should combine long-acting formulations (e.g., transdermal patches) together with short-acting formulations (e.g., chewing gum, lozenge, sublingual tablets, inhaler, oromucosal or nasal spray), as combination NRT is more effective than single NRT.[1254][1256][1257][1258][1259]

Ask about the time to first cigarette after waking. An answer of <30 minutes can indicate which patients may have more problems with nicotine dependence and can guide choice on dosing for transdermal nicotine patch.
Check your local formulary for any precautions, particularly if your patient has one or more comorbidity and/or is haemodynamically unstable.
Ensure a sufficient dose of NRT is prescribed to adequately address withdrawal symptoms.[1258]

For any patient who has an intention to quit smoking, consider using a nicotine analogue medication (e.g., varenicline, cytisinicline [also known as cytisine]) and NRT together as this is a highly effective combination for smoking cessation in adults.[1258][1260] Combination therapy for tobacco dependence is more effective than single-agent use.[1257]

Check local formulary for a full list of contraindications/cautions or seek pharmacist advice.
Mental health illness is NOT a contraindication to prescribing varenicline. However, varenicline should be used with caution in people with a pre-existing psychiatric illness as it may worsen symptoms.
Bupropion is an alternative option for smoking cessation but is less likely to result in successful quitting.[1254][1261] Consider the potential for drug-drug interactions.

Complete a referral to a tobacco dependency practitioner/service. Quit rates for hospitalised patients are highest when smoking cessation counselling begins in hospital and continues for more than one month after discharge.[1262]

Nicotine electronic cigarettes (also known as e-cigarettes or vapes) vaporise nicotine fluid formulation with a feel that approximates regular smoking. In some locations, such as the UK, nicotine-containing vapes may be considered as an additional or alternative option to conventional NRT in adults and supplied to inpatients under localised specialist tobacco services, where appropriate for the clinical setting.[1258]

severe disease

1st line – hospital admission

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1st line –

hospital admission

Admit patients with suspected or confirmed severe disease to an appropriate healthcare facility under the guidance of a specialist team as these patients are at risk of rapid clinical deterioration. For disease severity definitions, see Criteria.

Implement local infection prevention and control procedures.

Use the Clinical Frailty Scale (CFS) to assess baseline health and inform discussions on treatment expectations when appropriate and within an individualised assessment of frailty.[401] Clinical Frailty Scale Opens in new window

Do not use the CFS for younger people, people with stable long-term disabilities (e.g., cerebral palsy), learning disabilities, or autism. Make an individualised assessment of frailty in these people, using clinical assessment and alternative scoring methods.[401]
Evidence for the use of the CFS in COVID-19 is evolving despite limitations in the reporting on its application in practice.[690] Patients with a score between 4-9 had significantly increased mortality compared with those with a score of 1-3 in one systematic review and meta-analysis.[691] Each 1-point increase in score was associated with a 12% increase in mortality.[692] However, another systematic review and meta-analysis found that there was no difference in short-term mortality between frail and non-frail patients.[693] A more nuanced understanding of frailty and outcomes is needed, and caution is required in placing too much emphasis on the influence of frailty on the prognosis of older people.[694]

Assess your patient’s level of frailty

Practical tip

Frailty is a distinctive health state related to the ageing process in which multiple body systems gradually lose their in-built reserves.[1161] See Frailty.

Ask about your patient’s capability 2 weeks BEFORE this acute episode (with input from carers if relevant).
Use the Clinical Frailty Scale (CFS) if your patient is aged ≥65 years old.[1162] Dalhousie University: Clinical Frailty Scale Opens in new window The National Institute for Health and Care Excellence recommends using the CFS when a person is admitted to hospital with COVID-19.[1163]
- This tool is a practical aid to identify frailty, but should not be relied on in isolation.
- A higher pre-hospital frailty score is associated with an increased risk of adverse outcomes including mortality in-hospital and up to12 months; readmission within 30 days; extended length of stay; discharge to a nursing home, residential care, hospital, or a high level of care; and functional decline.[1164] For patients with COVID-19 specifically, higher levels of frailty are reported in some but not all studies to have an increased mortality risk.[1159][1165][1166][1167]
If your patient scores 6 or higher, seek senior advice on appropriate local referral for holistic review, which should include a discussion about their treatment expectations and care goals.[1162]
Help to implement multidisciplinary care and tailor the management approach according to what the patient values most.[1168]

Baseline neurological assessment

Reported neurological manifestations associated with COVID-19 include acute ischaemic and haemorrhagic stroke.[1159]
Generally a patient with an acute condition (e.g., an infection and illness-related hypotension) is at increased risk of stroke.[1204][1205][1206] This risk is even higher in anyone with a history of stroke.
Compare the baseline assessment with the patient’s known pre-COVID-19 neurological status. This could be done by asking the patient, family, and carers about the patient’s functional ability before becoming ill (based on expert opinion).
- This should reduce the risk of misattributing neurological signs on admission to the previous diagnosis of stroke.
If there is a change in neurological status during admission, repeat the neurological assessment in case of a new stroke.
Following assessment, ensure the right level of patient supervision (e.g., relating to the risk of confusion at night and the risk of falls associated with frailty).
- A patient with a history of stroke is at increased risk of falling and injury.[1207]

Guidance on when to stop isolation varies widely across locations.

The World Health Organization recommends 10 days of isolation for symptomatic patients, and 5 days of isolation for asymptomatic patients (based on very low-certainty evidence). Rapid antigen testing may be used to reduce the period of isolation.[85]
This guidance varies and you should consult your local public health guidance for more information.

Plus – set an escalation plan/consider ceiling of intervention

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Plus –

set an escalation plan/consider ceiling of intervention

Treatment recommended for ALL patients in selected patient group

An escalation plan should include:[1169]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of intervention (e.g., suitability for intubation or intensive care admission).
It should take account of advance care plans, including legally binding advance directives.[1159][1169]
It should be guided by your conversations with the patient about their individual wishes, including discussion to help them reach an informed decision about the likely benefit-risk balance of higher-intensity interventions.
Review the decision on CPR at intervals, and especially when an individual’s condition or expressed wishes change.[1170]

Assess and document mental capacity (the ability to make a specific decision at the time that the decision needs to be made).[1171] Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[1172] Assessments should follow the principles in the Act.[1172]
If your patient is assessed to lack mental capacity, consult with their next of kin to make ‘best interests’ decisions, bearing in mind what is known about the patient’s own previously expressed preferences.[1172] According to the 2005 Mental Capacity Act in England and Wales, if a patient is ‘unbefriended’ (i.e., has nobody to represent their best interests who is not paid to provide care) and a decision is not time-critical, you should seek an independent mental capacity advocate (IMAC) to perform this role.[1173] Check the appropriate legislation for your territory.

Consider – oxygen therapy

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Consider –

oxygen therapy

Additional treatment recommended for SOME patients in selected patient group

Start supplemental oxygen therapy immediately in any patient with emergency signs (i.e., obstructed or absent breathing, severe respiratory distress, central cyanosis, shock, coma and/or convulsions), or any patient without emergency signs and hypoxaemia.[85]

Target SpO₂ to ≥94% during resuscitation in adults and children with emergency signs who require emergency airway management and oxygen therapy. Once the patient is stable, a target SpO₂ >90% in children and non-pregnant adults, and ≥92% to 95% in pregnant women, is recommended. Nasal prongs or a nasal cannula are preferred in young children.[85]
Some guidelines recommend that SpO₂ should be maintained no higher than 96%.[696]
Some centres may recommend different SpO₂ targets in order to support prioritisation of oxygen flow for the most severely ill patients in hospital.

Consider positioning techniques (e.g., high supported sitting), and airway clearance management to optimise oxygenation and assist with secretion clearance in adults.

Consider awake prone positioning in severely ill patients who require supplemental oxygen.[85]
Awake prone positioning reduced the risk of endotracheal intubation compared with usual care. However, it did not significantly reduce mortality, ventilator-free days, length of stay in the intensive care unit or hospital, or escalation of oxygen modality. Adverse events were uncommon.[697]

Monitor patients closely for signs of progressive acute hypoxaemic respiratory failure.[85]

The World Health Organization recommends high-flow oxygen (HFNO), continuous positive airway pressure [CPAP], or non-invasive ventilation (helmet or face mask interface) in hospitalised patients with severe disease and acute hypoxaemic respiratory failure not needing emergent intubation, rather than standard oxygen therapy.[85]

Choice depends on factors such as availability of devices and the supply of oxygen, personal comfort and experience, and patient-specific considerations (e.g., claustrophobia with CPAP or non-invasive ventilation masks, nasal discomfort with HFNO).

Oxygen therapy in your patient with asthma

If your patient’s asthma is stable, follow guideline recommendations for oxygen saturation target for the presenting acute condition (i.e., COVID-19).[1263]

Measure resting oxygen saturation in all patients with asthma with any acute illness.[1263] This is routine practice in patients with COVID-19.

If COVID-19 triggers an acute exacerbation of the patient’s asthma, current opinion is to follow standard guideline recommendations for managing an acute exacerbation of asthma in adults.[1178][1196]

The Global Initiative for Asthma recommends controlled oxygen to maintain saturations between 93% and 95% for an acute asthma exacerbation.[1178]
Be aware that pulse oximetry may overestimate oxygen saturation in patients with darker skin tones.[1178]
Hypercapnia in asthma is a near fatal sign showing a patient is tiring and needs ventilatory support.[1196] Intensive care support is needed immediately.[1196]

Oxygen therapy in your patient with COPD

If your patient with comorbid COPD is suitable for full escalation of care refer for consideration of ventilation support if they are:

Severely hypoxaemic (PaO₂ <7.3 kPa [<54.8 mmHg]) despite oxygen therapy (based on expert opinion)
Hypercapnic (PaCO₂ >6 kPa [>45 mmHg]) with respiratory acidosis (pH <7.35)[1263]
AND/OR
Exhibiting changes in mental status (confusion, coma).

If your patient with comorbid COPD develops type 2 respiratory failure and it has been agreed that they are not suitable for full escalation of care involving intensive care unit admission:

Follow the guidance on oxygen as below
Discuss with your senior or respiratory expert whether ward-based non-invasive ventilation is suitable.

Practical tip

Take the same care when prescribing any supplemental oxygen in patients at risk of type 2 respiratory failure with COVID-19 as you would for patients with any other acute medical condition. Oxygen therapy for these patients should almost always be controlled. High-flow nasal oxygen (HFNO) is therefore not suitable for these patients. HFNO may be considered in patients not at risk of type 2 respiratory failure, but with severe hypoxaemia.[1195] Be aware that this should be prescribed by a senior decision-maker and should only ever be used with careful observation and repeat ABG measurements (based on expert opinion).

Measure resting oxygen saturations and be aware of additional factors to consider when prescribing oxygen therapy in a patient with COPD who is hypoxic.

Guidelines on emergency oxygen use (not specifically for COVID-19) from the British Thoracic Society recommend that any patient with COPD requiring oxygen supplementation needs an arterial blood gas (ABG) measurement.[1263]
Re-check ABG after 30 to 60 minutes in all patients.[1263]

If a patient with comorbid COPD is critically ill (e.g., shock, sepsis) and needs high levels of oxygen:

The British Thoracic Society (BTS) guideline on emergency oxygen use (not specifically for COVID-19) recommends an initial target oxygen saturation in line with the recommendation for patients without COPD.[1263] Evidence suggests that targeting an upper oxygen saturation level of 96% may be preferred compared with a higher level.[1264][1265] Follow your local hospital protocol on target oxygen saturations recommended in your hospital during the COVID-19 pandemic for acutely ill patients
Subsequently, you may need to adjust to controlled oxygen therapy with a target oxygen saturation range of 88% to 92% depending on the ABG results.[1263]

If a patient with comorbid COPD is acutely but not critically ill and is at risk of hypercapnic failure (including any patient with moderate or severe COPD, particularly if on long-term oxygen therapy, or with an alert card, or with a previous history of hypercapnic respiratory failure):[1263]

Use an initial target oxygen saturation of 88% to 92%
Check ABG and recheck after 30 to 60 minutes.

If a patient with comorbid COPD is acutely but not critically ill and is NOT at risk of hypercapnic respiratory failure (e.g., stable, mild COPD with minimal symptoms):

Use an initial target oxygen saturation as recommended by guidelines for the presenting acute condition.
- Evidence suggests that for most acutely ill patients targeting an upper oxygen saturation level of 96% may be preferred compared with a higher level.[1264][1265] This target saturation level may be lower depending on local hospital oxygen supplies (follow your local protocol)
Measure ABG as soon as possible[1263]
Subsequently, you may need to adjust to controlled oxygen therapy with a target oxygen saturation range of 88% to 92% depending on the ABG results.[1263]

Plus – symptom management and supportive care

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Plus –

symptom management and supportive care

Treatment recommended for ALL patients in selected patient group

Monitor patients closely for signs of clinical deterioration, and respond immediately with appropriate supportive care interventions.[85]

Fluids and electrolytes

Use cautious fluid management in adults and children without tissue hypoperfusion and fluid responsiveness as aggressive fluid resuscitation may worsen oxygenation.[85]
Correct any electrolyte or metabolic abnormalities, such as hyperglycaemia or metabolic acidosis, according to local protocols.[698]

Assess fluid status and manage fluid balance particularly closely

Be aware that hypovolaemia may be difficult to assess in a person with heart failure and/or CKD.

Assess:[1266]
- Pulse
- Blood pressure
- Peripheral perfusion
- Jugular venous pressure
- For pulmonary and peripheral oedema
- For postural hypotension.
Establish your patient’s baseline blood pressure as the fall from baseline and association with any symptoms (such as pre-syncope or syncope) is more significant than absolute systolic blood pressure (SBP).

Heart failure

A patient with heart failure may need fluid resuscitation. If needed, this should follow senior review and include close fluid balance monitoring, ideally with central venous pressure monitoring (based on expert opinion).

Be aware that an SBP of <90 mmHg may suggest hypotension, but a patient on medication for chronic heart failure can have a baseline SBP of <90 mmHg.
Consider and seek advice on transferring your patient to a setting with a more intensive level of care before initiating fluid resuscitation.

CKD

A patient with CKD who is hypovolaemic, particularly if in shock, needs immediate fluid resuscitation.

Reassess your patient after initial fluid challenge.
If they do not rapidly stabilise:
- Seek senior input and
- Consider transferring your patient to a setting with a more intensive level of care.

Check baseline kidney function and monitor closely

Check baseline kidney function and monitor closely, especially if your patient has risk factors for AKI, including a history of CKD, diabetes, and/or heart failure.[1174]

Patients with CKD, diabetes, and/or heart failure who also have COVID-19 will be at increased risk of AKI, which may be related to, among other factors, fever, dehydration, and use of non-steroidal anti-inflammatory drugs.
- AKI in patients with COVID-19 may be common (although exact prevalence is uncertain). AKI is associated with increased mortality.[1163] See Complications.
Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[1159]

If your patient with COVID-19 is admitted to hospital, check kidney function on admission and ensure regular monitoring.[1159]

For patients with CKD, diabetes, and/or heart failure:[1174]
- Compare kidney function with last available results, and follow local protocol for detecting AKI
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion)
- Monitor for and respond to oliguria.

Continue to monitor fluid balance particularly closely

Maintaining optimal fluid status is critical but it can be hard to achieve in all patients with COVID-19.[1163] Seek senior advice, particularly for complex patients, such as those with heart failure and/or CKD.

There is a significant risk of pulmonary oedema with fluid resuscitation in patients with heart failure and/or CKD so monitor closely (every hour initially).
Inpatient monitoring should include:
- Regular clinical assessment of volume status (pulse, BP, jugular venous pressure [JVP], and check for pulmonary and peripheral oedema)
- Fluid balance (input/output chart) and daily weight
- Kidney function check, at least daily.
Consider bladder catheterisation if urinary output is difficult to measure, but be aware of increased risk of infection and trauma.
Patients with greater clinical complexity, such as those with heart failure and/or AKI Stage 2 or worse, or advanced CKD, may need coronary care unit/high dependency unit care to include central venous pressure or pulmonary artery catheterisation monitoring, especially in the context of fluid resuscitation.[1267]

Practical tip

Always be mindful of signs of cardiogenic shock including elevated lactate, hypotension, worsening end-organ function, oliguria and altered mental status. Early and aggressive management is key to survival and requires immediate involvement of specialists including heart failure specialists (based on expert opinion).

It’s important to know when to de-escalate fluid therapy. Consider early senior input to support this decision.

If a patient has been volume overloaded with fluid (signs include raised pulse rate, raised respiratory rate due to pulmonary oedema, lung crepitations, hypoxaemia and a raised JVP):

Immediately stop fluid administration
Ask for senior help
Consider intravenous diuretics, and
Arrange an urgent chest x-ray or lung ultrasound if pulmonary oedema is suspected (based on expert opinion).

Unless there are extenuating circumstances, diuretics and intravenous fluids are not generally given together (based on expert opinion).

Input from an intensive care specialist and/or cardiologist and/or nephrologist may be needed.

Breathlessness and cough

Keep the room cool, and encourage relaxation, breathing techniques, and changing body positions. Identify and treat any reversible causes of breathlessness (e.g., pulmonary oedema, pulmonary embolism, COPD, asthma). Consider a trial of oxygen, if available.[401]
For the management of cough, advise patients to avoid lying on their back as this makes coughing ineffective, and follow your local guidelines for treating acute cough.[401]

Anxiety, delirium, and agitation

Identify and treat any underlying or reversible causes (e.g., offer reassurance, treat hypoxia, correct metabolic or endocrine abnormalities, address co-infections, minimise use of drugs that may cause or worsen delirium, treat substance withdrawal, maintain normal sleep cycles, treat pain or breathlessness).[85][401]
Low doses of haloperidol (or another suitable antipsychotic) can be considered for agitation.[85]
Non-pharmacological interventions are the mainstay for the management of delirium when possible, and prevention is key.[699]

Baseline cognitive and delirium assessments with collateral history

Use a validated scoring system that is feasible in the acute setting, such as the abbreviated mental test score/10 (AMTS/10).[1208][1209] British Geriatrics Society: Abbreviated Mental Test Score. 2018 Opens in new window
- Be aware that, while highly specific, the AMTS may underestimate the degree of cognitive impairment and more detailed assessment may be required in selected patients.[1210]
The collateral history establishes whether the patient’s cognition is stable, or if any decline in cognition and function has been gradual or acute.
A standardised cognitive assessment score is useful for monitoring for any clinical improvement, and for establishing needs on discharge. This score is often best interpreted alongside a functional assessment, usually performed by a trained occupational therapist.
Although the score may not represent the person's usual baseline for cognition due to the impact of the acute condition and its treatment, it is still good practice to record and repeat it when the person has recovered (based on expert opinion).

Delirium

Use a screening tool to detect probable delirium, such as:
- The 4AT.[1212][1211][1213][1214]
  - More information on calculating the 4AT has been produced by the Scottish Intercollegiate Guidelines Network. 4AT calculator Opens in new window
- The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC) if your patient is in a critical care setting or in the recovery room after surgery.[1212]
  - Recommended by the UK National Institute for Health and Care Excellence (NICE) as specifically designed for these settings, but training is needed, which may limit implementation.[1212]

People living with dementia are at increased risk of delirium when they are admitted to hospital and throughout their admission.[1211][1216]
Frailty increases the risk of delirium threefold during hospital admission.[1215]

Help with orientation; make sure patients have their own glasses and/or hearing aids
Get patients mobilised as soon as possible
Control pain adequately
Identify and treat superadded infections promptly
Keep well hydrated and help patients to eat adequately
Monitor and maintain regular bowel and bladder function
Use supplementary oxygen according to guideline recommendations.

Arrange a medication review with an experienced healthcare professional:[1211]

Calculate the anticholinergic burden (ACB) score.[1218]
A score of 3 or more may increase the risk of delirium within 24-48 hours of admission.[1219]
Consider discontinuing or substituting anticholinergic drugs where possible, but be aware of the need to taper some medications to avoid withdrawal side effects such as nausea and sweating.[1220]

Challenges specifically related to COVID-19 include:[1217]

The need for isolation, which may exacerbate delirium in some patients
The ability to regularly monitor patients for delirium, which may be affected by staffing and time resources available.

More info: Investigations

Initial investigations for a patient with delirium

If a patient has delirium, check for and treat life-threatening causes:[1211]

Hypoxia
Low blood glucose
Hypotension
Drug intoxication or withdrawal, including alcohol withdrawal.

Other investigations include (based on expert opinion):

Full blood count, electrolytes, renal function, thyroid function tests, liver function tests, calcium, glucose, CRP, folate, and vitamin B12
Blood cultures (if bacteraemia is suspected)
Urine culture
Chest x-ray.

Advanced non-routine investigations such as CT head may be needed, depending on specific clinical findings. Discuss with your senior.[1211]

Check for and treat any reversible causes of delirium.[1212] These include:

Pain
Infection
Poor nutrition
Constipation
Dehydration
Medications
- Ask about recently prescribed medications, especially opioid analgesics, anxiolytics, sedatives, antipsychotics, or medicines with strong anticholinergic properties
- Consider calculating a total anticholinergic burden score
Environment (including immobility, poor sleep, sensory impairment such as ear wax or loss of glasses).

The mnemonic PINCH ME may be helpful as an aide memoire for the underlying causes of delirium superimposed on dementia.[1221]

Management of a patient with delirium in hospital and long-term care

Manage patients with delirium initially, if possible with non-pharmacological treatment as recommended in management of delirium in a non-COVID-19 context.[1159][1212]

Reduce disorientation by providing a well-lit room, with a clock and calendar visible (e.g., on the wall).
Encourage and facilitate family, friends, and carers to visit the patient, within restrictions of your visiting policy as determined by current levels of community COVID-19 transmission.
Use verbal and non-verbal techniques to de-escalate conflict and distress.

The British Geriatrics Society has stated that in the context of management of a patient with COVID-19, it may be necessary to progress to pharmacological management earlier than would normally be considered in other circumstances because the risk of transmission of infection causing harm to others may be considered to be greater than potential harm to the individual.[1217]
The UK NICE guideline on delirium recommends short-term use of haloperidol (usually for less than 1 week), but it is not suitable in all patients and must never be used in patients with Parkinson’s disease or in patients with dementia with Lewy bodies.[1212]
- Take particular care to closely monitor and regularly review older people with frailty when prescribing haloperidol for acute delirium. They are particularly at risk of adverse neurological and cardiac effects of this drug.[1222]
  - A baseline ECG and correction of electrolyte abnormalities is recommended before starting haloperidol.
  - Prescribe at the lowest dose and for the shortest length of time possible.
  - During treatment, cardiac and electrolyte monitoring is recommended, as is monitoring for extrapyramidal adverse effects.
The evidence on the efficacy of antipsychotics for delirium is inconclusive, and hospital protocols may vary.[1211] Follow your local hospital protocol for choice of medication.
Always start at the lowest dose for antipsychotic drugs and titrate carefully according to symptoms.[1159][1212] Only ever use oral or intramuscular medication (never intravenous) for this purpose (based on expert opinion).

Evidence: Risks and safe withdrawal of antipsychotics in older people

Antipsychotics are associated with increased mortality in people with dementia.

A Cochrane review found very low certainty evidence that typical antipsychotics such as haloperidol improve agitation, and may improve psychosis slightly in people with Alzheimer’s disease and vascular dementia. Atypical antipsychotics probably reduce agitation. Both types increase the risk of somnolence and extrapyramidal symptoms.[1223]
A network meta-analysis found that people who take atypical antipsychotics for behavioural and psychological symptoms of dementia may have a small improvement in behavioural and psychological symptoms but have increased safety risks including cerebrovascular adverse events compared with those taking placebo.[1224]
Contrary to popular belief, long-term antipsychotic prescriptions can be safely withdrawn in most people with dementia once behaviour has settled.[1225]

Document the diagnosis of delirium clearly.[1212][1211]

Mouth care

An important part of overall patient care in hospitalised patients who are ventilated or non-ventilated and those undergoing step-down or end-of-life care.[700]

Mental health symptoms

Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia or depression as appropriate.[85]

Mental state examination

Do a mental state examination as the clinical situation allows and if the patient is responsive (based on expert opinion).

The mental state examination is one of the main clinical tools routinely used in psychiatric practice, aiding diagnosis and guiding further management. Mood is one of the assessed domains.

Consider assessing depression by using the PHQ-9 questionnaire.[1233]

This is self-administered and takes less than 3 minutes to complete.
Results indicate severity of depressive symptoms.
A score of 5 or above should trigger a referral to your liaison psychiatry service (based on expert opinion).

Depression has been reported to be a common finding in people hospitalised with COVID-19.[1159]

Consider other factors that may be influencing the patient’s mental state (e.g., the effect of any illicit drug use or alcohol).[1234]

Plus – review diabetes medication (NEVER stop insulin in a person with type 1 diabetes)

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Plus –

review diabetes medication (NEVER stop insulin in a person with type 1 diabetes)

Treatment recommended for ALL patients in selected patient group

Practical tip

Contact your hospital’s diabetes specialist team for support in managing any patient with COVID-19 and diabetes.

Never stop basal insulin (long-acting/background insulin [e.g., glargine or degludec]) in a patient with type 1 diabetes who presents with an acute illness, including COVID-19.[1188]

Insulin deficiency (e.g., due to delayed or missed doses) will rapidly cause ketoacidosis.[1188]

Be aware that COVID-19 appears to increase the risk of potentially life-threatening diabetes emergencies including:[1184]

Hyperglycaemia with ketones
Diabetic ketoacidosis (DKA)
Hyperosmolar hyperglycaemic state (HHS).

This is the case in patients with COVID-19 with and without known diabetes.

Check the following on admission to hospital:[1184]

Blood glucose in all patients
Blood ketones in all patients with diabetes (type 1 and type 2) and any patient who has a blood glucose on admission >12 mmol/L (>216 mg/dL)
HbA1c
- Admission HbA1c may give you an indication of your patient’s previous diabetes control and may influence your treatment on discharge (based on expert opinion).

Diagnose DKA in your patient with COVID-19 if:[1189]

Diabetes/hyperglycaemia: blood glucose ≥11.1 mmol/L (≥200 mg/dL) or prior history of diabetes
Ketosis: blood beta-hydroxybutyrate ≥3 mmol/L or urine ketone strip ≥2+
Metabolic Acidosis: blood pH <7.3 and/or bicarbonate <18 mmol/L.

Practical tip

In euglycaemic ketoacidosis, which may occur in people who have been taking sodium-glucose cotransporter-2 (SGLT2) inhibitors, the glucose level may not be significantly elevated.

The diagnosis of HHS is highly likely in the presence of:[1189]

Hyperglycaemia: blood glucose ≥33.3 mmol/L (≥600 mg/dL)
Hyperosmolarity: total serum osmolality ([(2 x Na) + glucose + urea]) >320 mOsm/kg or calculated effective serum osmolality ([(2 x Na) + glucose]) >300 mOsm/kg
AbSence of significant ketonaemia: blood beta-hydroxybutyrate <3 mmol/L or urine ketone strip <2+
Absence of acidosis: pH ≥7.3 and bicarbonate concentration ≥15 mmol/L.

Contact the diabetes specialist team and follow your local guidelines for management of DKA or HHS in patients with COVID-19, or if you suspect mixed DKA/HHS.

Diagnose hypoglycaemia if blood glucose <4 mmol/L (<72 mg/dL).

Follow your local protocol for management of hypoglycaemia.

Stop the following medication:[1184]

SGLT2 inhibitors prescribed for diabetes (e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin)
- SGLT2 inhibitors reduce blood glucose reabsorption in the kidneys (independently of insulin metabolism of glucose).[1190]
- They can mask underlying ketoacidosis as the patient may have a normal (or near normal) serum glucose level (euglycaemic ketoacidosis).[1190]
- If an SGLT2 inhibitor is continued during illness, for instance where it is being taken for its prognostic benefit for heart failure or to protect against progression of chronic kidney disease to kidney failure, be aware of the risk of euglycaemic ketoacidosis, although the risk is low.[1191] Monitor ketone levels on a daily basis (based on expert opinion). It is still reasonable to withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness (when people may be at greater risk for ketosis).[1192] Seek expert advice.
- Check blood ketones as urinary ketone measurement may be unreliable.
- Restart SGLT2 inhibitors when ketone values are normal, your patient’s condition has stabilised, and they are eating and drinking.[1186]
Metformin
- Metformin is contraindicated in patients with significant renal impairment (estimated GFR <30 mL/minute/1.73 m²), or metabolic acidosis (including lactic acidosis or DKA).
- It is also contraindicated if the patient is at risk of lactic acidosis: for example, with acute kidney injury or tissue hypoxia (including acute cardiac or respiratory failure), dehydration, or if they are to be fasted for a prolonged period.
- Consider restarting metformin depending on results of the patient’s blood lactate, kidney function, and arterial blood gases, as there is some evidence metformin may protect against progression to severe COVID-19.[1184]

The patient may need medication adjustment or to start insulin as a temporary measure if their usual anti-diabetes medication is stopped. Seek diabetes specialist team advice.

Follow local protocols regarding patients using wearable diabetes technology and seek diabetes specialist team advice.[1184]

Plus – venous thromboembolism (VTE) prophylaxis

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Plus –

venous thromboembolism (VTE) prophylaxis

Treatment recommended for ALL patients in selected patient group

Assess the patient’s risk of bleeding as soon as possible after admission, or by the time of the first consultant review, using a suitable risk assessment tool.[401]

If the patient is already on anticoagulation for another underlying condition, continue the current treatment dose of the anticoagulant, unless contraindicated or there is a change in clinical circumstances (e.g., bleeding develops or risk of bleeding increases).[401][685] Consider switching to low molecular weight heparin if the patient’s clinical condition is deteriorating and the patient is not currently on low molecular weight heparin.[401]
A systematic review and meta-analysis found that the use of oral anticoagulation prior to hospital admission was not associated with a reduced risk of intensive care unit admission and mortality. However, the review acknowledged that further trials are needed.[701]

Start VTE prophylaxis in all hospitalised patients, provided that there are no contraindications.[85][401][685] Start as soon as possible (within 14 hours of admission).[401]

A Cochrane review found that anticoagulants may reduce all‐cause mortality compared with no anticoagulants, but the evidence is very uncertain.[702]
A systematic review and meta-analysis found that the pooled odds of mortality between anticoagulated and non-anticoagulated hospitalised patients were similar, but lower in the standard prophylactic-dose group. Prophylactic-dose anticoagulation significantly decreased the odds of in-hospital death by 17% compared with no anticoagulation.[703]

Low molecular weight heparin, unfractionated heparin, or fondaparinux are the recommended options. Low molecular weight heparin is preferred over unfractionated heparin and fondaparinux, unless contraindicated.[85][401] Fondaparinux is the recommended option in patients with a history of heparin-induced thrombocytopenia.[704]

A meta-analysis found that low molecular weight heparin was associated with decreased intensive care unit admission, mechanical ventilation, hospital stay, and mortality compared with unfractionated heparin in hospitalised patients, and there was no difference in the incidence of bleeding.[705]
Mechanical thromboprophylaxis (e.g., intermittent pneumatic compression device) is recommended if anticoagulants are contraindicated or not available.[704]
There is limited evidence that direct oral anticoagulants (factor Xa inhibitors) are more effective than low molecular weight heparin in preventing VTE in hospitalised patients who are not acutely ill. However, guidelines do not recommend these agents, and further randomised controlled trials are needed.[706]
Consult a specialist for guidance on the choice of anticoagulant in special patient populations (e.g., children, pregnant and breastfeeding women, hepatic or renal impairment, active cancer).

Standard prophylaxis doses are generally recommended over intermediate or therapeutic doses in patients without an established indication for higher-dose anticoagulation.[85][685] However, recommendations vary and you should consult your local guidance.

In the UK, the National Institute for Health and Care Excellence recommends prophylaxis doses of low molecular weight heparin. However it also makes a conditional recommendation to consider treatment doses of low molecular weight heparin in those who may benefit. The decision should be carefully considered, and choice of the most appropriate dose regimen should be guided by bleeding risk, clinical judgement, and local protocols. For those who do not need supplemental oxygen, follow standard VTE prophylaxis guidelines.[401]
A Cochrane review found that higher-dose regimens resulted in little to no difference in all-cause mortality compared with lower-dose regimens in hospitalised patients; however, higher-dose regimens were associated with an increased risk of minor bleeding up to 30 days (high-certainty evidence). Higher-dose anticoagulants probably reduce pulmonary embolism and slightly increase major bleeding compared with lower-dose regimens up to 30 days (moderate-certainty evidence). Higher-dose anticoagulants may result in little or no difference in deep vein thrombosis, stroke, major adverse limb events, myocardial infarction, atrial fibrillation, or thrombocytopenia compared with lower-dose regimens up to 30 days (low-certainty evidence).[702]
Consult a specialist for guidance on the dose of anticoagulant in special patient populations (e.g., children, pregnant and breastfeeding women, hepatic or renal impairment, active cancer). Dose adjustments may be required in patients with extremes of body weight or renal impairment.[401]

Anticoagulation is generally continued until hospital discharge. Routine post-discharge VTE prophylaxis is generally not recommended, except in certain high-risk patients or if another indication for VTE prophylaxis exists.[85][685]

However, in the UK, the National Institute for Health and Care Excellence recommends treatment for a minimum of 7 days, including after discharge, if standard prophylaxis doses of heparin are used.[401] If therapeutic doses of heparin are used, the recommended treatment duration is 14 days or until hospital discharge, whichever is sooner.[401]
A systematic review and meta-analysis found that extended thromboprophylaxis (with either a direct oral anticoagulant or low molecular weight heparin at prophylaxis doses) administered for <35 days was significantly associated with a reduced risk of thrombosis and all-cause mortality in patients post-discharge who were at high risk of thromboembolism, without increasing the risk of major bleeding.[707]

Monitor patients for signs and symptoms suggestive of thromboembolism and proceed with appropriate diagnostic and management pathways if clinically suspected.[85] See Complications.

If the patient’s clinical condition changes, assess the risk of VTE, reassess the bleeding risk, and review VTE prophylaxis.[401]
Monitoring of clinical parameters during thromboprophylaxis depends on the anticoagulant and dose used. Consult your local protocols for more information.

Anticoagulation in your patient with CKD

Check your local drug formulary/renal handbook for details on prescribing anticoagulants for venous thromboembolism prophylaxis in patients with reduced kidney function (chronic kidney disease, acute kidney injury).

Patients with impairment of kidney function may have an increased risk of bleeding with certain anticoagulants and careful patient monitoring is needed.[1268]

Depending on the degree of impairment of your patient’s kidney function, you may need to:

Adjust the dose
Avoid certain anticoagulants.

Follow local drug formulary and hospital pharmacist’s guidance including on whether to monitor anti-factor Xa activity.

Seek a nephrologist’s and haematologist’s advice if the patient is receiving kidney replacement therapy.

Primary options

enoxaparin: consult specialist for guidance on dose

enoxaparin : consult specialist for guidance on dose

enoxaparin: consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

dalteparin : consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

Secondary options

fondaparinux: consult specialist for guidance on dose

fondaparinux : consult specialist for guidance on dose

fondaparinux: consult specialist for guidance on dose

heparin: consult specialist for guidance on dose

heparin : consult specialist for guidance on dose

heparin: consult specialist for guidance on dose

Consider – antimicrobials

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Consider –

antimicrobials

Additional treatment recommended for SOME patients in selected patient group

Consider empirical antibiotics if there is clinical suspicion of secondary bacterial infection.

Give within 1 hour of initial assessment for patients with suspected sepsis or if the patient meets high-risk criteria (or within 4 hours of establishing a diagnosis of secondary bacterial pneumonia); do not wait for microbiology results. Base the regimen on the clinical diagnosis (e.g., community-acquired pneumonia, hospital-acquired pneumonia, sepsis), local epidemiology and susceptibility data, and local treatment guidelines.[85][401]
Do not offer antibiotics for preventing or treating pneumonia if SARS-CoV-2, another virus, or a fungal infection is likely to be the cause.[401]

Seek specialist advice.

Consider seeking specialist advice for people who: are immunocompromised; have a history of infection with resistant organisms; have a history of repeated infective exacerbations of lung disease; are pregnant; or are receiving advanced respiratory or organ support.[401]
Seek specialist advice if there is a suspicion that the person has an infection with multidrug-resistant bacteria and may need a different antibiotic, or there is clinical or microbiological evidence of infection and the person's condition does not improve as expected after 48 to 72 hours of antibiotic treatment.[401]

Reassess antibiotic use daily.

De-escalate empirical therapy on the basis of microbiology results and clinical judgement. Regularly review the possibility of switching from intravenous to oral therapy. Duration of treatment should be as short as possible (e.g., 5 to 7 days). Antibiotic stewardship programmes should be in place.[85]
A meta-analysis found that the prevalence of antibiotic prescribing in patients with COVID-19 was 75%, which is significantly higher than the estimated prevalence of bacterial co-infection. Therefore, unnecessary antibiotic use is likely to be high in these patients.[708]

Treat laboratory-confirmed co-infections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[85]

Consider – corticosteroid

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Consider –

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations and evidence for the use of corticosteroids in patients with severe or critical COVID-19BMJ. 2023 Jan 12;380:57 [Citation ends].

Consider a systemic corticosteroid. Guideline recommendations vary.

The World Health Organization strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with severe disease. This recommendation is based on moderate-quality evidence that suggests systemic corticosteroids probably reduce 28-day mortality in patients with severe disease. There is no evidence directly comparing dexamethasone and hydrocortisone. The harms of treatment in this context are considered to be minor. It is unclear whether these recommendations can be applied to children or those who are immunocompromised.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends offering dexamethasone (or an alternative such as hydrocortisone or prednisolone when dexamethasone cannot be used or is unavailable) to people who need supplemental oxygen to meet their prescribed oxygen saturation levels, or who have a level of hypoxia that needs supplemental oxygen but who are unable to have or tolerate it. Treatment is for up to 10 days unless there is a clear indication to stop early.[401]
In the US, the Infectious Diseases Society of America recommends dexamethasone (or an alternative corticosteroid if dexamethasone is not available) for 10 days or until hospital discharge in hospitalised patients with severe disease.[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Evidence supports the use of corticosteroids in hospitalised patients.

A Cochrane review found that systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in hospitalised patients with symptomatic disease (moderate-certainty evidence), although the evidence is very uncertain about the effect on all-cause mortality up to 120 days. Evidence related to the most effective type, dose, or timing of corticosteroid is uncertain.[709]
A living systematic review and network meta-analysis found that corticosteroids probably reduce mortality compared with standard care.[710][711]
Evidence suggests that higher doses may be superior to lower doses in reducing mortality in patients with severe or critical disease.[712] However, the RECOVERY trial found that higher-dose corticosteroids significantly increased the risk of death compared with usual care (which included low-dose corticosteroids) in hospitalised patients who required either no oxygen or simple oxygen only.[713]
Evidence also suggests that shorter treatment courses may optimise the mortality benefit in hospitalised patients. An optimal duration of treatment was <7 days in one meta-analysis, with no additional survival benefit reported with ≥7 days of treatment.[714]

Monitor patients for adverse effects (e.g., hyperglycaemia, secondary infections, psychiatric effects, reactivation of latent infections) and assess for drug-drug interactions.

Manage your patient’s diabetes when they are taking corticosteroids

Giving corticosteroids to someone with diabetes will worsen their glycaemic control, so test blood glucose at least four times a day.[1269]

For patients with diabetes, use the same doses of corticosteroid as for patients without diabetes but adjust diabetes medication, as their diabetes control will get worse.
Synthetic corticosteroids can cause hyperglycaemia by affecting carbohydrate metabolism and inducing insulin resistance.[1270]
COVID-19 is also associated with increased insulin resistance as well as reduced insulin secretion from the pancreatic beta cells.[1269]
If hyperglycaemia does occur, rule out diabetic ketoacidosis or hyperosmolar hyperglycaemic state and follow your hospital protocol on managing blood glucose in patients with diabetes and COVID-19 taking corticosteroids.[1269]
- The recommended protocol by the UK-based National Inpatient Diabetes COVID-19 Response Group for the ward setting uses subcutaneous insulin.[1269]
- The group highlights that sulfonylureas are not recommended in this scenario due to potential impairment of beta cell function and likely severe insulin resistance.[1269]

When you stop the corticosteroid dose, glycaemic control will likely improve, although this may occur over a few days.

Follow your local protocol on titrating antidiabetic medication.

Monitor for psychiatric complications of corticosteroids

Check previous response to corticosteroids.

Although all patients should be monitored for adverse effects, the risk of depression, mania, panic disorder, or suicide during corticosteroid therapy has been reported to be higher in people who are already living with these conditions, but not consistently so.[1271]
Consider referral for psychiatric advice on whether to offer prophylactic medication.[1271]

Monitor for psychiatric adverse effects.

These may vary in severity and include among others:[1272]
- Anxiety and insomnia
- Severe mood changes, including manic states
- Cognitive impairment.
Effects seem to be dose-related and are more common with long-term regimens or long-acting formulations, and in older patients.[1271] This also stands true for patients who have neuropsychiatric adverse effects related to discontinuing long-term corticosteroid therapy.[1273]
Manic episodes and delirious states are the most common psychiatric adverse effects when starting corticosteroid treatment, whereas depression is most common during chronic therapy.[1271][1274]
Be mindful of a possible withdrawal reaction, which may present with weakness, fatigue, gastrointestinal symptoms, and delirium, as well as with psychiatric complications such as depression, when discontinuing corticosteroids.[1273]

If your patient develops psychiatric complications related to corticosteroids, liaise with the psychiatry team for advice on appropriate management (based on expert opinion).

This may include adjusting dose or earlier discontinuation of the corticosteroid therapy if the clinical situation allows.[1271]

Primary options

dexamethasone: children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone : children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone: children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days

hydrocortisone sodium succinate: children: consult specialist for guidance on dose; adults: 50 mg intravenously every 8 hours for 7-10 days

hydrocortisone sodium succinate : children: consult specialist for guidance on dose; adults: 50 mg intravenously every 8 hours for 7-10 days

hydrocortisone sodium succinate: children: consult specialist for guidance on dose; adults: 50 mg intravenously every 8 hours for 7-10 days

Secondary options

prednisolone: children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone : children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone: children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

methylprednisolone: children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 2-4 divided doses for 7-10 days

methylprednisolone : children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 2-4 divided doses for 7-10 days

methylprednisolone: children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 2-4 divided doses for 7-10 days

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

dexamethasone

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

hydrocortisone sodium succinate

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Secondary options

prednisolone

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

methylprednisolone

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Consider – antiviral

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Consider –

antiviral

Additional treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations and evidence for the use of remdesivir in patients with severe COVID-19BMJ. 2023 Jan 12;380:57 [Citation ends].

Consider the antiviral agent remdesivir. Guideline recommendations vary.

The World Health Organization conditionally recommends the intravenous antiviral remdesivir in adults with severe disease. This recommendation is based on low-certainty evidence that suggests remdesivir possibly reduces mortality, and moderate-certainty evidence that suggests it probably reduces the need for mechanical ventilation. Moderate-certainty evidence suggests that remdesivir probably has little or no impact on time to symptom improvement. There is insufficient evidence to make a recommendation around use in children.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends remdesivir as an option in hospitals in adults at high risk of serious illness, and children (aged 4 weeks to 17 years and weight ≥3 kg) who have pneumonia and need supplemental oxygen or who weigh ≥40 kg and have a high risk of serious illness.[401][682]
In the US, the Infectious Diseases Society of America recommends remdesivir for 5 days in patients who require supplemental oxygen.[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Remdesivir should be administered as soon as possible after onset of symptoms. The recommended treatment course for this indication is 5 to 10 days or until hospital discharge, whichever comes first.[398][401][402]

Evidence does not suggest any greater benefit with a 10-day course of remdesivir compared with a 5-day course, but suggests an increased risk of harm. There may be no benefit in completing the full course of remdesivir if the patient progresses.[401]

Despite guidelines recommending the use of remdesivir in patients with severe disease, evidence for its use is conflicting.

A Cochrane review found that remdesivir probably has little or no effect on all-cause mortality (up to 150 days) in hospitalised patients with moderate to severe disease compared with placebo or usual care (moderate-certainty evidence). Remdesivir probably increases the chance of clinical improvement up to day 28 slightly, and decreases the risk of clinical worsening within 28 days (moderate-certainty evidence).[715]
A 1-year follow-up of hospitalised patients in a randomised controlled trial found no long-term benefits (quality-of-life or symptom outcomes) for remdesivir compared with standard of care.[716]

Adverse effects include nephrotoxicity and hepatotoxicity.

Remdesivir may have little or no effect on acute kidney injury compared with placebo; however, the certainty of evidence is low.[771]
Transaminase elevations have been reported. Monitor liver function before starting treatment and during treatment as clinically appropriate. Consider discontinuing treatment if alanine aminotransferase (ALT) levels increase to ≥10 times the upper limit of normal. Discontinue treatment if ALT elevation is accompanied by signs or symptoms of liver inflammation.
Monitor prothrombin time before starting treatment and during treatment as clinically appropriate as increases in prothrombin time have been reported.

Hypersensitivity reactions, including infusion-related reactions and anaphylaxis, have been reported.

Administer in a setting where severe hypersensitivity reactions can be managed. Monitor patients during the infusion and observe for at least 1 hour after infusion.

Primary options

remdesivir: children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 5-10 days

remdesivir : children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 5-10 days

remdesivir: children ≥12 years of age and ≥40 kg and adults: 200 mg intravenously as a loading dose on day 1, followed by 100 mg every 24 hours for 5-10 days

Consider – interleukin-6 (IL-6) inhibitor

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Consider –

interleukin-6 (IL-6) inhibitor

Additional treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations and evidence for the use of IL-6 inhibitors in patients with severe or critical COVID-19BMJ. 2023 Jan 12;380:57 [Citation ends].

Consider an IL-6 inhibitor. Guideline recommendations vary.

The World Health Organization strongly recommends a single dose of an IL-6 inhibitor (tocilizumab or sarilumab) in adults with severe disease. IL-6 inhibitors may be administered in combination with corticosteroids and Janus kinase inhibitors, and should be initiated at the same time as systemic corticosteroids. This recommendation is based on high-certainty evidence that shows IL-6 inhibitors reduce mortality and the need for mechanical ventilation, and low-certainty evidence that suggests that IL-6 inhibitors may also reduce the duration of mechanical ventilation and hospitalisation. The evidence regarding the risk of severe adverse events is uncertain. The applicability of this recommendation to children is currently uncertain.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends a single dose of tocilizumab in hospitalised adults who are having systemic corticosteroids and need supplemental oxygen.[401][664]
In the US, the Infectious Diseases Society of America recommends a single dose of tocilizumab (or sarilumab if tocilizumab is not available) in hospitalised patients with progressive severe disease who have elevated markers of systemic inflammation in addition to standard care (i.e., corticosteroids).[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Evidence supports the use of IL-6 inhibitors.

A Cochrane review found that tocilizumab reduced all-cause mortality at day 28 (high-certainty evidence) compared with standard care alone or placebo. The evidence suggests uncertainty around the effect of tocilizumab on mortality after day 60. Evidence for an effect on these outcomes for sarilumab is very uncertain. Tocilizumab and sarilumab probably result in little or no increase in clinical improvement at day 28 (i.e., hospital discharge or improvement measured by triallist-defined scales) (moderate-certainty evidence). The evidence for clinical improvement after day 60 is very uncertain for both drugs.[718]
A living systematic review and network meta-analysis found that IL-6 inhibitors (with corticosteroids) probably reduce mortality (moderate-certainty evidence), are likely to reduce the need for mechanical ventilation (moderate-certainty evidence), and may reduce the duration of hospitalisation (moderate-certainty evidence) compared with standard care.[710][711]
IL-6 inhibitors may not be beneficial when used alone (without corticosteroids).[719]

Patients on IL-6 inhibitors are at increased risk of infection including active tuberculosis, invasive fungal infections, and opportunistic pathogens.

Routine blood work including neutrophil count, platelets, transaminases, and total bilirubin should be checked prior to initiation of therapy. All patients should be monitored for signs and symptoms of infection given the increased risk of immunosuppression in addition to systemic corticosteroids.[402]

Primary options

tocilizumab: children: consult specialist for guidance on dose; adults: 8 mg/kg intravenously as a single dose, maximum 800 mg/dose

tocilizumab : children: consult specialist for guidance on dose; adults: 8 mg/kg intravenously as a single dose, maximum 800 mg/dose

tocilizumab: children: consult specialist for guidance on dose; adults: 8 mg/kg intravenously as a single dose, maximum 800 mg/dose

sarilumab: adults: 400 mg intravenously as a single dose

sarilumab : adults: 400 mg intravenously as a single dose

sarilumab: adults: 400 mg intravenously as a single dose

Consider – Janus kinase (JAK) inhibitor

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Consider –

Janus kinase (JAK) inhibitor

Additional treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations and evidence for the use of JAK inhibitors in patients with severe or critical COVID-19BMJ. 2023 Jan 12;380:57 [Citation ends].

Consider a JAK inhibitor. Guideline recommendations vary.

The World Health Organization strongly recommends an oral JAK inhibitor (baricitinib) for 14 days or until hospital discharge (whichever is first) in adults with severe disease. Baricitinib may be administered in combination with corticosteroids and IL-6 inhibitors, and should be initiated at the same time as systemic corticosteroids. This recommendation is based on high-certainty evidence that baricitinib reduces mortality, and moderate-certainty evidence that baricitinib probably reduces the duration of mechanical ventilation and the length of hospital stay. The applicability of this recommendation to children is currently uncertain.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends baricitinib in hospitalised adults who: need supplemental oxygen, and are having or have completed a course of corticosteroids (unless contraindicated), and have no evidence of infection (other than SARS-CoV-2) that might be worsened by baricitinib. It may also be considered in children ≥2 years of age provided they meet the same criteria.[401]
In the US, the Infectious Diseases Society of America recommends baricitinib in hospitalised patients with severe disease, in addition to corticosteroid therapy. It may also be used in patients who cannot receive a corticosteroid due to a contraindication (in combination with remdesivir).[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Other drugs in this class include tofacitinib and ruxolitinib.

The World Health Organization recommends against using other drugs in this class unless baricitinib or IL-6 inhibitors are not available. The effects of tofacitinib or ruxolitinib on mortality, need for mechanical ventilation, and hospital length of stay remain uncertain and more trial evidence is needed.[402][654][655]

Evidence supports the use of JAK inhibitors.

A Cochrane review found that JAK inhibitors probably reduced all-cause mortality up to day 28 (moderate-certainty evidence) and up to day 60 (high-certainty evidence). They probably make little or no difference in improvement in clinical status or the rate of adverse events (moderate-certainty evidence). Baricitinib was the most often evaluated JAK inhibitor.[720]
A living systematic review and network meta-analysis found that JAK inhibitors probably reduce mortality (high-certainty evidence), reduce the duration of mechanical ventilation (high-certainty evidence), and reduce length of hospital stay (high-certainty evidence) compared with standard care.[710][711]

Patients are at increased risk of infection including active tuberculosis, invasive fungal infections, and opportunistic pathogens.[402]

Avoid use in patients with known active tuberculosis.
All patients should be monitored for signs and symptoms of infection given the increased risk of immunosuppression in addition to systemic corticosteroids.
Monitor full blood count with differential before and during treatment.

Baricitinib is not recommended in patients with severe renal or hepatic impairment.[402]

Baricitinib is not recommended in adults with an estimated glomerular filtration rate ≤15 mL/minute (≤30 mL/minute in children <9 years of age), or in patients on dialysis or renal replacement therapy. A dose reduction is recommended in patients with an estimated glomerular filtration rate ≤60 mL/minute.
Baricitinib has not been studied in patients with severe hepatic impairment and it is unknown whether a dose adjustment is required in these patients. It should only be used if the potential benefits outweigh the potential risks.
Use caution with tofacitinib and ruxolitinib in patients with moderate to severe renal impairment (including those on dialysis); a dose adjustment may be required.
Monitor renal and hepatic function before and during treatment.

Adverse effects include leukopenia, lymphopenia, thrombocytosis, anaemia, blood clotting abnormalities, hepatic impairment, and secondary infection.[402]

Other serious adverse effects include venous thrombosis and severe infections.

Take your patient’s risk of adverse effects into account when considering a JAK inhibitor

Check kidney function before starting a JAK inhibitor in your patient with CKD.

Check your local formulary as dose adjustments may be needed.
Baricitinib is not recommended if your patient is on dialysis, has end-stage kidney failure, or has acute kidney injury.[1193]
Ruxolitinib and tofacitinib should be used with caution in moderate to severe renal impairment and a dose adjustment may be required. Consult your local formulary and seek advice from the nephrology team.

Monitor kidney function particularly closely during JAK inhibitor treatment in your patient with CKD.

The US Food and Drug Administration (FDA) and the European Medicines Agency have issued warnings on the use of JAK inhibitors for certain groups of people taking these medications for chronic inflammatory conditions.[1275][1276] These warnings do not cover the short-term treatment of COVID-19, and a Cochrane systematic review did not find any increased risk of adverse events.[1277] It also found that JAK inhibitors probably reduce the risk of serious adverse events in people with COVID-19.[1277]

Primary options

baricitinib: children: consult specialist for guidance on dose; adults: 4 mg orally once daily for 14 days

baricitinib : children: consult specialist for guidance on dose; adults: 4 mg orally once daily for 14 days

baricitinib: children: consult specialist for guidance on dose; adults: 4 mg orally once daily for 14 days

Secondary options

tofacitinib: children and adults: consult specialist for guidance on dose

tofacitinib : children and adults: consult specialist for guidance on dose

tofacitinib: children and adults: consult specialist for guidance on dose

ruxolitinib: children and adults: consult specialist for guidance on dose

ruxolitinib : children and adults: consult specialist for guidance on dose

ruxolitinib: children and adults: consult specialist for guidance on dose

Consider – antipyretic/analgesic

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Consider –

antipyretic/analgesic

Additional treatment recommended for SOME patients in selected patient group

Paracetamol or ibuprofen are recommended.[85][401]

Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms. It is not recommended in pregnant women (especially in the third trimester) or children <6 months of age (age cut-offs vary by country).

NSAIDs in your patient with chronic kidney disease, heart failure, or asthma

Chronic kidney disease (CKD)

Avoid non-steroidal anti-inflammatory drugs (NSAIDs) in your patient with CKD.[1174]

Heart failure

Avoid NSAIDs as they increase the risk of worsening heart failure and hospitalisation with heart failure.[1177]

Asthma

NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[1178]

Primary options

paracetamol: children: consult local drug formulary for guidance on dose; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

paracetamol : children: consult local drug formulary for guidance on dose; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

paracetamol: children: consult local drug formulary for guidance on dose; adults: 500-1000 mg orally every 4-6 hours when required, maximum 4000 mg/day

ibuprofen: children: consult local drug formulary for guidance on dose; adults: 300-600 mg orally (immediate-release) every 6-8 hours when required, maximum 2400 mg/day

ibuprofen : children: consult local drug formulary for guidance on dose; adults: 300-600 mg orally (immediate-release) every 6-8 hours when required, maximum 2400 mg/day

ibuprofen: children: consult local drug formulary for guidance on dose; adults: 300-600 mg orally (immediate-release) every 6-8 hours when required, maximum 2400 mg/day

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

paracetamol

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

ibuprofen

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Plus – continue your patient's inhalers as prescribed for asthma or COPD if appropriate

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Plus –

continue your patient's inhalers as prescribed for asthma or COPD if appropriate

Treatment recommended for ALL patients in selected patient group

Patients with an acute medical condition can forget to tell you about their inhalers prescribed for COPD or asthma. Remember to check and prescribe if appropriate.

Many inhalers contain a combination of medications, so ensure no dual prescribing.
Patients with COPD or asthma who develop acute kidney injury with an estimated GFR <50 mL/minute/1.73 m² may need to temporarily stop their usual inhaled long-acting muscarinic antagonist, depending on which specific drug is used.
- Check local formulary or seek pharmacist advice.

Other prescribed medication

Patients with severe asthma or COPD who take oral corticosteroids as regular prescribed maintenance therapy should also continue to take these at the lowest dose possible, as their condition may deteriorate if these are stopped.[1178][1195]
Patients who take biological therapy for severe asthma should continue to take this treatment, unless specifically advised not to do so.[1178]

Plus – weigh up risks versus benefits of prescribed antihypertensive medication

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Plus –

weigh up risks versus benefits of prescribed antihypertensive medication

Treatment recommended for ALL patients in selected patient group

Despite initial concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, high-certainty evidence has found that the use of these drugs is not associated with severe disease or poor outcomes.[1198][1199][1200]

Do an individual clinical assessment
Consider the original indication for any RAAS inhibitors (ACE inhibitors, angiotensin-II receptor antagonists, mineralocorticoid receptor/aldosterone antagonists) and degree of prognostic benefit
If medication is temporarily withheld, consider when to re-introduce again once health improves.

Seek advice from the patient’s cardiology or nephrology team if they have complex conditions (e.g., on renal replacement therapy or immunosuppressive therapy).

Consider – plan for discharge and rehabilitation

Consider – palliative care

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Consider –

palliative care

Additional treatment recommended for SOME patients in selected patient group

Palliative care interventions should be made accessible at each institution that provides care for patients with COVID-19.

Identify whether the patient has an advance care plan and respect the patient’s priorities and preferences when formulating the patient’s care plan.[85]
Follow local palliative care guidelines.

There is a lack of data on palliative care in patients with COVID-19.

A Cochrane review found very low-certainty evidence for the efficacy of pharmacological interventions for palliative symptom relief, and no evidence on the safety of pharmacological interventions or safety and efficacy of non-pharmacological interventions for palliative symptom control. More evidence is needed to guide end-of-life management.[767]
A rapid systematic review of pharmacological strategies used for palliative care in these patients, the first international review of its kind, found that a higher proportion of patients required continuous subcutaneous infusions for medication delivery than is typically seen in the palliative care population. Modest doses of commonly used end-of-life medications were required for symptom control. However, these findings should be interpreted with caution due to the lack of data available.[721]

Plus – monitor comorbidities during hospital stay

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Plus –

monitor comorbidities during hospital stay

– ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

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–

ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

Treatment recommended for ALL patients in selected patient group

Monitor for acute worsening of respiratory symptoms and be aware that this may suggest a patient with comorbid asthma is having an acute exacerbation of their asthma.

Seek senior advice.
Follow standard guideline recommendations on assessing severity and managing an acute exacerbation of asthma in adults, even if COVID-19 is suspected as the trigger.[1196]
- See Acute asthma exacerbation in adults.
- Avoid using a nebuliser where possible. Consider whether it may be clinically appropriate to use a metered-dose inhaler delivered via a spacer device with a mouthpiece or tightly fitted face mask as an alternative delivery mechanism to a nebuliser.[1178] Follow your local protocols.
Start oral corticosteroids as clinically indicated for asthma exacerbations.[1178][1196]
Consider temporarily stopping any long-acting muscarinic antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a short-acting muscarinic antagonist (e.g., ipratropium) (based on expert opinion).
- This is due to concern over possible additive anticholinergic adverse effects.
- Ensure to re-prescribe the LAMA once the nebuliser treatment has been stopped.

– ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

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–

ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

Treatment recommended for ALL patients in selected patient group

If an exacerbation of COPD is suspected in a patient with COVID-19 and pre-existing COPD:

Seek senior or specialist advice.
Differentiate from other conditions, such as acute coronary syndrome, acute heart failure, and pneumonia, as well as from complications of COVID-19.[1195]
Follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[1195] See Acute exacerbation of COPD.
Consider using pressurised metered-dose inhalers, dry powder inhalers, or soft mist inhalers for drug delivery instead of nebulisers in non-critically ill patients not receiving ventilatory support.[1195] Follow your local guidance and protocols.
The Global Initiative for Chronic Obstructive Disease recommends continuing inhaled long-acting bronchodilators during an exacerbation, or starting them as soon as possible before discharge from hospital.[1195] This is an individualised clinical decision due to limited evidence.
Consider temporarily stoping any long-acting muscarinic antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a short-acting muscarinic antagonist (e.g., ipratropium) (based on expert opinion).
- This is due to concern over possible additive anticholinergic adverse effects.
- Ensure the LAMA is re-prescribed once the nebuliser treatment has been stopped.

– monitor and manage blood glucose during the hospital admission

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–

monitor and manage blood glucose during the hospital admission

Treatment recommended for ALL patients in selected patient group

Monitor blood glucose levels at least four times a day (every 4-6 hours or, if eating, pre-meal and before bedtime) in any acutely ill patient with diabetes mellitus.[1226]

Follow your local protocol on blood glucose monitoring for inpatients with COVID-19 who have diabetes.

Hyperglycaemia during the ongoing hospital admission

Act promptly to treat hyperglycaemia to avoid diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS), which are medical emergencies.

Follow your local hospital protocol if your patient’s capillary blood glucose is ≥12 mmol/L (≥216 mg/dL).
- COVID-19 guidance generally emphasises the importance of managing hyperglycaemia.[1185]
- Exclude DKA or HHS, both of which require specific urgent management.
- Consider other conditions associated with hyperglycaemia, such as sepsis.[1184]
Be aware that the following medications may be associated with hyperglycaemia and may need to be reviewed:[1228]
- Corticosteroids (e.g., dexamethasone)
- Some beta-blockers (e.g., propranolol, atenolol)
- Thiazide diuretics (e.g., hydrochlorothiazide)
- Some second-generation antipsychotics (e.g., olanzapine, clozapine)
- Certain fluoroquinolone antibiotics (e.g., ciprofloxacin)
- Calcineurin inhibitors (e.g., ciclosporin, tacrolimus)
- Protease inhibitors (e.g., ritonavir).
If your patient does not have DKA/HHS but has a blood glucose above 12 mmol/L (216 mg/dL), follow your local protocols on management of hyperglycaemia in patients with COVID-19.[1227]
- Be aware that patients with type 2 diabetes in ICU may have significant degrees of insulin resistance. Seek support from your diabetes specialist inpatient team in these circumstances.[1227]

Practical tip

Ask for expert advice from the inpatient diabetes team.

Hypoglycaemia during the ongoing hospital admission

Monitor blood glucose and adjust medication in response to illness and hospital meal times, to reduce the risk of hypoglycaemic episodes.

Approximately 1 in 5 inpatients with diabetes in England and Wales were found to have had a hypoglycaemic episode during their hospital stay.[1229]

Causes of hypoglycaemia include:[1230]

Recovery from an acute illness
- Patients recovering from COVID-19 may have a rapid change in insulin requirements, so monitor and adjust insulin regimens carefully[1227]
Accidental interruptions to patient feeding, which may occur especially when patients with COVID-19 are nursed in the prone position[1184]
Reducing doses of corticosteroids, particularly dexamethasone in patients with COVID-19[1227]
Insulin or oral hypoglycaemic medication error
Wrong timing of insulin in relation to meals
Patients eating less but taking the same amount of diabetes medication
No bedtime snacks
Reduced appetite or vomiting.

In the acute hospital setting, meal times may be interrupted or may not always be at exactly the same time each day.
- Give sulfonylurea medication before or with food. Check local drug formulary for more specific guidance on timing of dose in relation to food for specific sulfonylurea.
- Never give sulfonylurea medication at bedtime and, if the patient is taking a dose with their evening meal, consider reducing the evening dose to reduce the risk of nocturnal hypoglycaemia (based on expert opinion).

Practical tip

Bedtime snacks can reduce the risk of early morning hypoglycaemia.[1229]

Consider intervening if the blood glucose falls below 6 mmol/L (108 mg/dL) (‘looming/impending’ hypoglycaemia) if on insulin or on sulfonylureas.

These patients are at high risk of progressing to hypoglycaemia.
Give carbohydrates as recommended in the hypoglycaemia guideline and follow your local protocol.[1230]

Retest blood glucose at 10 to 15 minutes to determine response to treatment
Never stop the next scheduled dose of insulin if the hypoglycaemia has been corrected. This can cause rebound hyperglycaemia and DKA in people with type 1 diabetes.
- Seek diabetes inpatient specialist team advice on whether a review of your patient’s insulin regimen is needed.

Follow local protocols and guidance on self-monitoring of blood glucose by patients in hospital.

These may have been adapted in the context of patients with COVID-19. For instance, some hospitals in the US have been utilising ‘virtual’ formats, including expanding self-management protocols, to reduce need for personal protective equipment, where it is safe to do so.[1185]

– check your patient’s feet

– review current treatment for depression

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–

review current treatment for depression

Treatment recommended for ALL patients in selected patient group

Ask your patient which medications they are taking for their mental health. Alternatively, review their primary care records for relevant information (if available).

Drug-drug interactions and their associated adverse effects of particular relevance to patients with COVID-19 include sedation, cardiotoxicity (QT prolongation), and respiratory depression.[1159]

Consider that antidepressants may be used in the treatment of conditions other than depression, and drugs other than antidepressants may be used to treat depression.

Prescribe the patient’s usual antidepressant medication, unless there are good reasons not to (based on expert opinion).

If antidepressants are stopped abruptly, the patient may develop discontinuation symptoms.[1235]
The severity of symptoms of discontinuation may vary, but it may be unpleasant and may complicate the management of the acute medical condition.[1235][1236]

When reviewing current medication, look out for:

Current and previous adverse effects
Recent changes in dose
Recent switches from a different class of medication
Pharmacological nuances of specific depression subtypes (e.g., it is likely that patients suffering from psychotic depression would be co-prescribed an antipsychotic)
Augmenting strategies that may be in use when treating resistant depression (e.g., lithium or quetiapine augmentation of a selective serotonin-reuptake inhibitor [SSRI]).

Consider drug-drug interactions.

Antidepressant medications may cause pharmacokinetic (by inhibiting the CYP450 pathway) and pharmacodynamic interactions with medications used for other conditions.[1237][1238] Consider this issue for all medications prescribed in patients with COVID-19 as well as any experimental therapies (see the Emerging section).

Consider psychiatric complications when prescribing non-psychotropic drugs.

Take particular care when prescribing corticosteroids, anticonvulsants, and antiparkinsonian medication.

Consider adverse effects, which may include the following.[1238]

QT prolongation, arrhythmias, increased heart rate, or postural hypotension with tricyclic antidepressants. Check ECG, especially in people at risk of arrhythmias.
Hyponatraemia, caused by antidepressants, especially SSRIs, and compounded by other co-prescribed drugs (e.g., diuretics). Check your patient’s serum electrolytes.
Serotonin syndrome (altered mental state, agitation, tremor, hyper-reflexia, clonus, muscle rigidity, diaphoresis, tachycardia, increased bowel sounds, temperature >38℃), especially with polypharmacy and/or overdose of a serotonergic agent.[1239][1240] See Serotonin syndrome.
- Be particularly aware of increased risk of serotonin syndrome in patients with end-stage renal disease on SSRIs. Treating depression in patients with renal impairment requires a multidisciplinary approach and demands extra caution.
Hepatotoxicity. Adjust doses of antidepressants in patients with hepatic impairment if necessary and avoid drugs that are known to be hepatotoxic.
Gastrointestinal bleeding. SSRIs are associated with an increased risk of gastrointestinal bleeding.[1238] Risk is particularly increased when co-prescribed with aspirin, non-steroidal anti-inflammatory drugs, or oral anticoagulants.[1241][1242] Try to avoid this combination of drugs.[1238] Monitor closely and consider gastroprotection with proton-pump inhibitors if SSRI use cannot be avoided.[1238]

Ask your patient about non-pharmacological treatments for their depression and check the current level of support in the community.

This may include other health professionals involved in their care, charities, family and social networks, and psychological therapy.

Practical tip

– consider referral to the liaison psychiatry team

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–

consider referral to the liaison psychiatry team

Treatment recommended for ALL patients in selected patient group

Consider a referral to the liaison psychiatry team/service for any patient with established or suspected depression who is admitted to hospital with an acute condition.[1246][1247]

Referral may not be required if there are no concerns that depression and/or its management (e.g., medication) may be impacting on the acute condition (based on expert opinion).
Follow your local protocols/referral pathways in your hospital.
COVID-19 is associated with psychiatric and neurological manifestations including depression.[1159]

Evidence: Depression and adherence to treatment post-discharge

Comorbid depression is linked to poor adherence with recommended physical health treatments, from medication to rehabilitation.[1248]

This may lead to worse clinical outcomes, including higher readmission risk.[1249][1250][1251]
Most importantly, affective symptoms including depression have been linked with excess mortality, though a causal link remains to be proven.[1252][1253]

– manage nicotine dependence and support current smokers to stop smoking

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manage nicotine dependence and support current smokers to stop smoking

Treatment recommended for ALL patients in selected patient group

Evidence suggests there is an association with increased severity of COVID-19 and risk of death in hospitalised patients who smoke tobacco.

In light of this, in addition to the well-recognised harms, the World Health Organization recommends smoking cessation using evidence-based methods.[1255]

Offer nicotine replacement therapy (NRT) and other smoking cessation pharmacotherapies for all inpatients who smoke if there are no contraindications.[1254]

Advise that:[1254]

Nicotine is highly addictive but is not the cause of smoking-related harms
NRT prevents rapid withdrawal during admission, which can be distressing and uncomfortable
There are several highly effective treatment options that offer the best chance of stopping smoking when combined with specialist support.

Ask about the time to first cigarette after waking. An answer of <30 minutes can indicate which patients may have more problems with nicotine dependence and can guide choice on dosing for transdermal nicotine patch.
Check your local formulary for any precautions, particularly if your patient has one or more comorbidity and/or is haemodynamically unstable.
Ensure a sufficient dose of NRT is prescribed to adequately address withdrawal symptoms.[1258]

Check local formulary for a full list of contraindications/cautions or seek pharmacist advice.
Mental health illness is NOT a contraindication to prescribing varenicline. However, varenicline should be used with caution in people with a pre-existing psychiatric illness as it may worsen symptoms.
Bupropion is an alternative option for smoking cessation but is less likely to result in successful quitting.[1254][1261] Consider the potential for drug-drug interactions.

critical disease

1st line – intensive/critical care unit admission

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1st line –

intensive/critical care unit admission

Admit or transfer patients with critical disease (i.e., presence of acute respiratory distress syndrome, sepsis, or septic shock) to an intensive/critical care unit under the guidance of a specialist team.[85] For disease severity definitions, see Criteria.

Discuss the risks, benefits, and potential outcomes of treatment options with patients and their families, and allow them to express preferences about their management. Take their wishes and expectations into account when considering the ceiling of treatment. Use decision support tools if available. Put treatment escalation plans in place, and discuss any existing advance care plans or advance decisions to refuse treatment with patients who have pre-existing advanced comorbidities.[401]
Implement local infection prevention and control procedures.

Assess your patient’s level of frailty

Practical tip

Frailty is a distinctive health state related to the ageing process in which multiple body systems gradually lose their in-built reserves.[1161] See Frailty.

Ask about your patient’s capability 2 weeks BEFORE this acute episode (with input from carers if relevant).
Use the Clinical Frailty Scale (CFS) if your patient is aged ≥65 years old.[1162] Dalhousie University: Clinical Frailty Scale Opens in new window The National Institute for Health and Care Excellence recommends using the CFS when a person is admitted to hospital with COVID-19.[1163]
- This tool is a practical aid to identify frailty, but should not be relied on in isolation.
- A higher pre-hospital frailty score is associated with an increased risk of adverse outcomes including mortality in-hospital and up to12 months; readmission within 30 days; extended length of stay; discharge to a nursing home, residential care, hospital, or a high level of care; and functional decline.[1164] For patients with COVID-19 specifically, higher levels of frailty are reported in some but not all studies to have an increased mortality risk.[1159][1165][1166][1167]
If your patient scores 6 or higher, seek senior advice on appropriate local referral for holistic review, which should include a discussion about their treatment expectations and care goals.[1162]
Help to implement multidisciplinary care and tailor the management approach according to what the patient values most.[1168]

Set an escalation plan/consider ceiling of intervention

An escalation plan should include:[1169]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of intervention (e.g., suitability for intubation or intensive care admission).
It should take account of advance care plans, including legally binding advance directives.[1159][1169]
It should be guided by your conversations with the patient about their individual wishes, including discussion to help them reach an informed decision about the likely benefit-risk balance of higher-intensity interventions.
Review the decision on CPR at intervals, and especially when an individual’s condition or expressed wishes change.[1170]

Assess and document mental capacity (the ability to make a specific decision at the time that the decision needs to be made).[1171] Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[1172] Assessments should follow the principles in the Act.[1172]
If your patient is assessed to lack mental capacity, consult with their next of kin to make ‘best interests’ decisions, bearing in mind what is known about the patient’s own previously expressed preferences.[1172] According to the 2005 Mental Capacity Act in England and Wales, if a patient is ‘unbefriended’ (i.e., has nobody to represent their best interests who is not paid to provide care) and a decision is not time-critical, you should seek an independent mental capacity advocate (IMAC) to perform this role.[1173] Check the appropriate legislation for your territory.

Withhold antihypertensives and/or diuretics if hypotensive

Consider withholding antihypertensives and/or diuretics in a patient with a history of hypertension, coronary heart disease, heart failure, stroke, or CKD if your patient:

Is shocked or hypotensive, or
Has a blood pressure ≥40 mmHg lower than their baseline, or
Has developed orthostatic hypotension or has postural symptoms (based on expert opinion).
- Orthostatic hypotension is defined, by consensus, as a fall in systolic blood pressure ≥20 mmHg and/or a fall in diastolic blood pressure ≥10 mmHg within 3 minutes of standing.[1278]
- In practice, the standing blood pressure may be taken after the person has been standing for at least 1 minute.[1279]

Establish your patient’s baseline blood pressure and assess volume status.

Patients with treated heart failure may have chronically low blood pressure (e.g., systolic BP ≤90 mmHg). If their systolic blood pressure falls by >10 to 15 mmHg and is associated with symptoms, it may be appropriate to withhold medications that may lower blood pressure but have no or little prognostic benefit for heart failure (such as amlodipine, doxazosin).
- Consider changing the time of administration of medication that has a prognostic benefit for heart failure (e.g., sacubitril/valsartan, beta-blockers) to night time, or splitting or reducing the dose (based on expert opinion).
- You may need expert review.

If diuretics are withheld in a patient with heart failure and/or CKD, close monitoring is needed as fluid can quickly accumulate.

Be aware that sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of medication with a prognostic benefit for both heart failure and CKD, also have a weak diuretic effect.[1280]

If antihypertensives or diuretics have been withheld during the acute illness, consider restarting them before discharge if clinically appropriate (based on expert opinion).

Restart one at a time at a lower dose and ask the primary care practitioner to titrate back to normal dose.
- Most patients won’t tolerate restarting all medications at the original doses in one go.
- If it is not clinically appropriate to restart these medicines before discharge, ensure that the patient has follow-up to decide when the medications can be re-introduced.
- Ensure you have communicated clearly to the doctor who will be reviewing your patient following discharge.

Guidance on when to stop isolation varies widely across locations.

The World Health Organization recommends 10 days of isolation for symptomatic patients, and 5 days of isolation for asymptomatic patients (based on very low certainty evidence). Rapid antigen testing may be used to reduce the period of isolation.[85]
This guidance varies and you should consult your local public health guidance for more information.

Plus – symptom management and supportive care

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Plus –

symptom management and supportive care

Treatment recommended for ALL patients in selected patient group

Consider fluid and electrolyte management, antimicrobial treatment, and symptom management as appropriate.

See Severe COVID-19 above for more detailed information.

Implement standard interventions to prevent complications associated with critical illness.[85]

The management of sepsis and septic shock in patients with COVID-19 is beyond the scope of this topic. See Complications.

Treat laboratory-confirmed co-infections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[85]

Check baseline kidney function and monitor closely

Check baseline kidney function and monitor closely, especially if your patient has risk factors for AKI, including a history of CKD, diabetes, and/or heart failure.[1174]

Patients with CKD, diabetes, and/or heart failure who also have COVID-19 will be at increased risk of AKI, which may be related to, among other factors, fever, dehydration, and use of non-steroidal anti-inflammatory drugs.
- AKI in patients with COVID-19 may be common (although exact prevalence is uncertain). AKI is associated with increased mortality.[1163] See Complications.
Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[1159]

If your patient with COVID-19 is admitted to hospital, check kidney function on admission and ensure regular monitoring.[1159]

For patients with CKD, diabetes, and/or heart failure:[1174]
- Compare kidney function with last available results, and follow local protocol for detecting AKI
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion)
- Monitor for and respond to oliguria.

Assess fluid status and manage fluid balance particularly closely

Be aware that hypovolaemia may be difficult to assess in a person with heart failure and/or CKD.

Assess:[1266]
- Pulse
- Blood pressure
- Peripheral perfusion
- Jugular venous pressure
- For pulmonary and peripheral oedema
- For postural hypotension.
Establish your patient’s baseline blood pressure as the fall from baseline and association with any symptoms (such as pre-syncope or syncope) is more significant than absolute systolic blood pressure (SBP).

Heart failure

Be aware that an SBP of <90 mmHg may suggest hypotension, but a patient on medication for chronic heart failure can have a baseline SBP of <90 mmHg.
Consider and seek advice on transferring your patient to a setting with a more intensive level of care before initiating fluid resuscitation.

CKD

A patient with CKD who is hypovolaemic, particularly if in shock, needs immediate fluid resuscitation.

Reassess your patient after initial fluid challenge.
If they do not rapidly stabilise:
- Seek senior input and
- Consider transferring your patient to a setting with a more intensive level of care.

Continue to monitor fluid balance particularly closely

There is a significant risk of pulmonary oedema with fluid resuscitation in patients with heart failure and/or CKD so monitor closely (every hour initially).
Inpatient monitoring should include:
- Regular clinical assessment of volume status (pulse, BP, jugular venous pressure [JVP], and check for pulmonary and peripheral oedema)
- Fluid balance (input/output chart) and daily weight
- Kidney function check, at least daily.
Consider bladder catheterisation if urinary output is difficult to measure, but be aware of increased risk of infection and trauma.
Patients with greater clinical complexity, such as those with heart failure and/or AKI Stage 2 or worse, or advanced CKD, may need coronary care unit/high dependency unit care to include central venous pressure or pulmonary artery catheterisation monitoring, especially in the context of fluid resuscitation.[1267]

Practical tip

It’s important to know when to de-escalate fluid therapy. Consider early senior input to support this decision.

If a patient has been volume overloaded with fluid (signs include raised pulse rate, raised respiratory rate due to pulmonary oedema, lung crepitations, hypoxaemia and a raised JVP):

Immediately stop fluid administration
Ask for senior help
Consider intravenous diuretics, and
Arrange an urgent chest x-ray or lung ultrasound if pulmonary oedema is suspected (based on expert opinion).

Unless there are extenuating circumstances, diuretics and intravenous fluids are not generally given together (based on expert opinion).

Input from an intensive care specialist and/or cardiologist and/or nephrologist may be needed.

NSAIDs in your patient with chronic kidney disease, heart failure, or asthma

Chronic kidney disease (CKD)

Avoid non-steroidal anti-inflammatory drugs (NSAIDs) in your patient with CKD.[1174]

Heart failure

Avoid NSAIDs as they increase the risk of worsening heart failure and hospitalisation with heart failure.[1177]

Asthma

NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[1178]

Baseline cognitive and delirium assessments with collateral history

Use a validated scoring system that is feasible in the acute setting, such as the abbreviated mental test score/10 (AMTS/10).[1208][1209] British Geriatrics Society: Abbreviated Mental Test Score. 2018 Opens in new window
- Be aware that, while highly specific, the AMTS may underestimate the degree of cognitive impairment and more detailed assessment may be required in selected patients.[1210]
The collateral history establishes whether the patient’s cognition is stable, or if any decline in cognition and function has been gradual or acute.
A standardised cognitive assessment score is useful for monitoring for any clinical improvement, and for establishing needs on discharge. This score is often best interpreted alongside a functional assessment, usually performed by a trained occupational therapist.
Although the score may not represent the person's usual baseline for cognition due to the impact of the acute condition and its treatment, it is still good practice to record and repeat it when the person has recovered (based on expert opinion).

Delirium

Use a screening tool to detect probable delirium, such as:
- The 4AT.[1212][1211][1213][1214]
  - More information on calculating the 4AT has been produced by the Scottish Intercollegiate Guidelines Network. 4AT calculator Opens in new window
- The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or the Intensive Care Delirium Screening Checklist (ICDSC) if your patient is in a critical care setting or in the recovery room after surgery.[1212]
  - Recommended by the UK National Institute for Health and Care Excellence (NICE) as specifically designed for these settings, but training is needed, which may limit implementation.[1212]

People living with dementia are at increased risk of delirium when they are admitted to hospital and throughout their admission.[1211][1216]
Frailty increases the risk of delirium threefold during hospital admission.[1215]

Help with orientation; make sure patients have their own glasses and/or hearing aids
Get patients mobilised as soon as possible
Control pain adequately
Identify and treat superadded infections promptly
Keep well hydrated and help patients to eat adequately
Monitor and maintain regular bowel and bladder function
Use supplementary oxygen according to guideline recommendations.

Arrange a medication review with an experienced healthcare professional:[1211]

Calculate the anticholinergic burden (ACB) score.[1218]
A score of 3 or more may increase the risk of delirium within 24-48 hours of admission.[1219]
Consider discontinuing or substituting anticholinergic drugs where possible, but be aware of the need to taper some medications to avoid withdrawal side effects such as nausea and sweating.[1220]

Challenges specifically related to COVID-19 include:[1217]

The need for isolation, which may exacerbate delirium in some patients
The ability to regularly monitor patients for delirium, which may be affected by staffing and time resources available.

More info: Investigations

Initial investigations for a patient with delirium

If a patient has delirium, check for and treat life-threatening causes:[1211]

Hypoxia
Low blood glucose
Hypotension
Drug intoxication or withdrawal, including alcohol withdrawal.

Other investigations include (based on expert opinion):

Full blood count, electrolytes, renal function, thyroid function tests, liver function tests, calcium, glucose, CRP, folate, and vitamin B12
Blood cultures (if bacteraemia is suspected)
Urine culture
Chest x-ray.

Advanced non-routine investigations such as CT head may be needed, depending on specific clinical findings. Discuss with your senior.[1211]

Check for and treat any reversible causes of delirium.[1212] These include:

Pain
Infection
Poor nutrition
Constipation
Dehydration
Medications
- Ask about recently prescribed medications, especially opioid analgesics, anxiolytics, sedatives, antipsychotics, or medicines with strong anticholinergic properties
- Consider calculating a total anticholinergic burden score
Environment (including immobility, poor sleep, sensory impairment such as ear wax or loss of glasses).

The mnemonic PINCH ME may be helpful as an aide memoire for the underlying causes of delirium superimposed on dementia.[1221]

Management of a patient with delirium in hospital and long-term care

Manage patients with delirium initially, if possible with non-pharmacological treatment as recommended in management of delirium in a non-COVID-19 context.[1159][1212]

Reduce disorientation by providing a well-lit room, with a clock and calendar visible (e.g., on the wall).
Encourage and facilitate family, friends, and carers to visit the patient, within restrictions of your visiting policy as determined by current levels of community COVID-19 transmission.
Use verbal and non-verbal techniques to de-escalate conflict and distress.

The British Geriatrics Society has stated that in the context of management of a patient with COVID-19, it may be necessary to progress to pharmacological management earlier than would normally be considered in other circumstances because the risk of transmission of infection causing harm to others may be considered to be greater than potential harm to the individual.[1217]
The UK NICE guideline on delirium recommends short-term use of haloperidol (usually for less than 1 week), but it is not suitable in all patients and must never be used in patients with Parkinson’s disease or in patients with dementia with Lewy bodies.[1212]
- Take particular care to closely monitor and regularly review older people with frailty when prescribing haloperidol for acute delirium. They are particularly at risk of adverse neurological and cardiac effects of this drug.[1222]
  - A baseline ECG and correction of electrolyte abnormalities is recommended before starting haloperidol.
  - Prescribe at the lowest dose and for the shortest length of time possible.
  - During treatment, cardiac and electrolyte monitoring is recommended, as is monitoring for extrapyramidal adverse effects.
The evidence on the efficacy of antipsychotics for delirium is inconclusive, and hospital protocols may vary.[1211] Follow your local hospital protocol for choice of medication.
Always start at the lowest dose for antipsychotic drugs and titrate carefully according to symptoms.[1159][1212] Only ever use oral or intramuscular medication (never intravenous) for this purpose (based on expert opinion).

Evidence: Risks and safe withdrawal of antipsychotics in older people

Antipsychotics are associated with increased mortality in people with dementia.

A Cochrane review found very low certainty evidence that typical antipsychotics such as haloperidol improve agitation, and may improve psychosis slightly in people with Alzheimer’s disease and vascular dementia. Atypical antipsychotics probably reduce agitation. Both types increase the risk of somnolence and extrapyramidal symptoms.[1223]
A network meta-analysis found that people who take atypical antipsychotics for behavioural and psychological symptoms of dementia may have a small improvement in behavioural and psychological symptoms but have increased safety risks including cerebrovascular adverse events compared with those taking placebo.[1224]
Contrary to popular belief, long-term antipsychotic prescriptions can be safely withdrawn in most people with dementia once behaviour has settled.[1225]

Document the diagnosis of delirium clearly.[1212][1211]

Baseline neurological assessment

Reported neurological manifestations associated with COVID-19 include acute ischaemic and haemorrhagic stroke.[1159]
Generally a patient with an acute condition (e.g., an infection and illness-related hypotension) is at increased risk of stroke.[1204][1205][1206] This risk is even higher in anyone with a history of stroke.
Compare the baseline assessment with the patient’s known pre-COVID-19 neurological status. This could be done by asking the patient, family, and carers about the patient’s functional ability before becoming ill (based on expert opinion).
- This should reduce the risk of misattributing neurological signs on admission to the previous diagnosis of stroke.
If there is a change in neurological status during admission, repeat the neurological assessment in case of a new stroke.
Following assessment, ensure the right level of patient supervision (e.g., relating to the risk of confusion at night and the risk of falls associated with frailty).
- A patient with a history of stroke is at increased risk of falling and injury.[1207]

Plus – review diabetes medication (NEVER stop insulin in a person with type 1 diabetes)

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Plus –

review diabetes medication (NEVER stop insulin in a person with type 1 diabetes)

Treatment recommended for ALL patients in selected patient group

Practical tip

Contact your hospital’s diabetes specialist team for support in managing any patient with COVID-19 and diabetes.

Never stop basal insulin (long-acting/background insulin [e.g., glargine or degludec]) in a patient with type 1 diabetes who presents with an acute illness, including COVID-19.[1188]

Insulin deficiency (e.g., due to delayed or missed doses) will rapidly cause ketoacidosis.[1188]

Be aware that COVID-19 appears to increase the risk of potentially life-threatening diabetes emergencies including:[1184]

Hyperglycaemia with ketones
Diabetic ketoacidosis (DKA)
Hyperosmolar hyperglycaemic state (HHS).

This is the case in patients with COVID-19 with and without known diabetes.

Check the following on admission to hospital:[1184]

Blood glucose in all patients
Blood ketones in all patients with diabetes (type 1 and type 2) and any patient who has a blood glucose on admission >12 mmol/L (>216 mg/dL)
HbA1c
- Admission HbA1c may give you an indication of your patient’s previous diabetes control and may influence your treatment on discharge (based on expert opinion).

Diagnose DKA in your patient with COVID-19 if:[1189]

Diabetes/hyperglycaemia: blood glucose ≥11.1 mmol/L (≥200 mg/dL) or prior history of diabetes
Ketosis: blood beta-hydroxybutyrate ≥3 mmol/L or urine ketone strip ≥2+
Metabolic Acidosis: blood pH <7.3 and/or bicarbonate <18 mmol/L.

Practical tip

In euglycaemic ketoacidosis, which may occur in people who have been taking sodium-glucose cotransporter-2 (SGLT2) inhibitors, the glucose level may not be significantly elevated.

The diagnosis of HHS is highly likely in the presence of:[1189]

Hyperglycaemia: blood glucose ≥33.3 mmol/L (≥600 mg/dL)
Hyperosmolarity: total serum osmolality ([(2 x Na) + glucose + urea]) >320 mOsm/kg or calculated effective serum osmolality ([(2 x Na) + glucose]) >300 mOsm/kg
AbSence of significant ketonaemia: blood beta-hydroxybutyrate <3 mmol/L or urine ketone strip <2+
Absence of acidosis: pH ≥7.3 and bicarbonate concentration ≥15 mmol/L.

Contact the diabetes specialist team and follow your local guidelines for management of DKA or HHS in patients with COVID-19, or if you suspect mixed DKA/HHS.

Diagnose hypoglycaemia if blood glucose <4 mmol/L (<72 mg/dL).

Follow your local protocol for management of hypoglycaemia.

Stop the following medication:[1184]

SGLT2 inhibitors prescribed for diabetes (e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin)
- SGLT2 inhibitors reduce blood glucose reabsorption in the kidneys (independently of insulin metabolism of glucose).[1190]
- They can mask underlying ketoacidosis as the patient may have a normal (or near normal) serum glucose level (euglycaemic ketoacidosis).[1190]
- If an SGLT2 inhibitor is continued during illness, for instance where it is being taken for its prognostic benefit for heart failure or to protect against progression of chronic kidney disease to kidney failure, be aware of the risk of euglycaemic ketoacidosis, although the risk is low.[1191] Monitor ketone levels on a daily basis (based on expert opinion). It is still reasonable to withhold SGLT2 inhibitors during times of prolonged fasting, surgery, or critical medical illness (when people may be at greater risk for ketosis).[1192] Seek expert advice.
- Check blood ketones as urinary ketone measurement may be unreliable.
- Restart SGLT2 inhibitors when ketone values are normal, your patient’s condition has stabilised, and they are eating and drinking.[1186]
Metformin
- Metformin is contraindicated in patients with significant renal impairment (estimated GFR <30 mL/minute/1.73 m²), or metabolic acidosis (including lactic acidosis or DKA).
- It is also contraindicated if the patient is at risk of lactic acidosis: for example, with acute kidney injury or tissue hypoxia (including acute cardiac or respiratory failure), dehydration, or if they are to be fasted for a prolonged period.
- Consider restarting metformin depending on results of the patient’s blood lactate, kidney function, and arterial blood gases, as there is some evidence metformin may protect against progression to severe COVID-19.[1184]

The patient may need medication adjustment or to start insulin as a temporary measure if their usual anti-diabetes medication is stopped. Seek diabetes specialist team advice.

Follow local protocols regarding patients using wearable diabetes technology and seek diabetes specialist team advice.[1184]

Plus – venous thromboembolism (VTE) prophylaxis

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Plus –

venous thromboembolism (VTE) prophylaxis

Treatment recommended for ALL patients in selected patient group

If not already started, start VTE prophylaxis in all hospitalised patients, provided there are no contraindications.[85][685][775]

See Severe COVID-19 above for more detailed information on VTE prophylaxis. However, recommendations for patients with critical disease may differ from those for severe disease. Consult your local guidelines.
In the UK, the National Institute for Health and Care Excellence recommends a prophylactic dose of a low molecular weight heparin to young people and adults who need high-flow nasal oxygen, continuous positive airway pressure, non-invasive ventilation, or invasive mechanical ventilation, and who do not have an increased bleeding risk. An intermediate or treatment dose of a low molecular weight heparin is only recommended in these patients as part of a clinical trial.[401]

Evidence for VTE prophylaxis is limited in patients with critical disease.

A systematic review and meta-analysis of nearly 28,000 hospitalised patients found that both intermediate-dose and therapeutic-dose anticoagulation decreased the risk of thrombotic events in critically ill patients in the intensive care unit compared with prophylactic-dose anticoagulation, but these regimens were associated with an increased bleeding risk and unchanged in-hospital mortality.[765]
Another smaller systematic review and meta-analysis found no difference between escalated doses and standard prophylaxis dosing in terms of impact on mortality in critically ill patients. However, there was a reduced risk of pulmonary embolism in the escalated dose group.[766]

Anticoagulation in your patient with CKD

Patients with impairment of kidney function may have an increased risk of bleeding with certain anticoagulants and careful patient monitoring is needed.[1268]

Depending on the degree of impairment of your patient’s kidney function, you may need to:

Adjust the dose
Avoid certain anticoagulants.

Follow local drug formulary and hospital pharmacist’s guidance including on whether to monitor anti-factor Xa activity.

Seek a nephrologist’s and haematologist’s advice if the patient is receiving kidney replacement therapy.

Primary options

enoxaparin: consult specialist for guidance on dose

enoxaparin : consult specialist for guidance on dose

enoxaparin: consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

dalteparin : consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

Secondary options

heparin: consult specialist for guidance on dose

heparin : consult specialist for guidance on dose

heparin: consult specialist for guidance on dose

fondaparinux: consult specialist for guidance on dose

fondaparinux : consult specialist for guidance on dose

fondaparinux: consult specialist for guidance on dose

Consider – high-flow nasal oxygen or non-invasive ventilation

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Consider –

high-flow nasal oxygen or non-invasive ventilation

Additional treatment recommended for SOME patients in selected patient group

The World Health Organization recommends high-flow nasal oxygen (HFNO), continuous positive airway pressure (CPAP), or non-invasive ventilation (helmet or face mask interface) in hospitalised patients with severe or critical disease and acute hypoxaemic respiratory failure not needing emergent intubation, rather than standard oxygen therapy. Choice depends on factors such as availability of devices and the supply of oxygen, personal comfort and experience, and patient-specific considerations (e.g., claustrophobia with CPAP or non-invasive ventilation masks, nasal discomfort with HFNO).[85]

In the UK, the National Institute for Health and Care Excellence recommends CPAP in patients with hypoxaemia that is not responding to supplemental oxygen with a fraction of inspired oxygen of ≥0.4 (40%), and escalation to invasive mechanical ventilation would be an option but it is not immediately needed or it is agreed that respiratory support should not be escalated beyond CPAP. Ensure there is access to critical care providers for advice, regular review, and prompt escalation of treatment if needed, and regular assessment and management of symptoms alongside non-invasive respiratory support. Consider using HFNO for people when: they cannot tolerate CPAP but need humidified oxygen at high flow rates; maximal conventional oxygen is not maintaining their target oxygen saturations and they do not need immediate invasive mechanical ventilation or escalation to invasive mechanical ventilation is not suitable, and CPAP is not suitable; or they need a break from CPAP (e.g., mealtimes, skin pressure relief, mouth care), need humidified oxygen or nebulisers (or both), or need weaning from CPAP. Do not routinely offer HFNO as the main form of respiratory support for people with respiratory failure in whom escalation to invasive mechanical ventilation would be appropriate.[401]
Patients with hypercapnia, haemodynamic instability, multi-organ failure, or abnormal mental status should generally not receive HFNO, although emerging data suggest that it may be safe in patients with mild to moderate and non-worsening hypercapnia. Patients with hypoxaemic respiratory failure and haemodynamic instability, multi-organ failure, or abnormal mental status should not receive these treatments in place of other options such as invasive ventilation.[85]
Airborne precautions are recommended for these interventions (including bubble CPAP) due to uncertainty about the potential for aerosolisation.[85] However, CPAP and HFNO do not appear to be associated with significant additional air or surface viral contamination compared with supplemental oxygen.[736] Despite the trend to avoid HFNO, it has been shown to have a similar risk of aerosol generation to standard oxygen masks.[737] A systematic review and meta-analysis found no association between HFNO and non-invasive ventilation and aerosol generation-increased airborne pathogen detection.[738]

Consider awake prone positioning in severely ill patients who require HFNO or non-invasive ventilation.[85]

In the UK, the National Institute for Health and Care Excellence recommends considering awake prone positioning for hospitalised patients who are not intubated and have higher oxygen needs.[401]
Awake prone positioning reduced the risk of endotracheal intubation compared with usual care. However, it did not significantly reduce mortality, ventilator-free days, length of stay in the intensive care unit or hospital, or escalation of oxygen modality. Adverse events were uncommon.[697]

Monitor patients closely for acute deterioration.

If patients do not improve after a short trial of these interventions, they require urgent endotracheal intubation.[85][696]

Limited evidence suggests that non-invasive ventilation reduces the need for intubation, improves resource utilisation, may be associated with better outcomes, and is safe.[726]

There is no certain evidence that non-invasive respiratory support increases or decreases mortality in patients with COVID-19 acute respiratory failure.[725]
Indirect and low-certainty evidence suggests that non-invasive ventilation probably reduces mortality in patients with COVID-19, similar to invasive mechanical ventilation, but may increase the risk of viral transmission. HFNO may reduce mortality compared with no HFNO.[727][728]
HFNO was superior to non-invasive ventilation for acute respiratory failure in terms of decreasing mortality. However, there was no significant difference in intubation rates and length of hospital stay between the two groups.[729][730]
HFNO may reduce intubation rate and 28-day intensive care unit mortality, and may improve 28-day ventilator-free days compared with conventional oxygen therapy in patients with acute respiratory failure. However, large-scale randomised controlled trials are necessary.[731]
The RECOVERY-RS trial (an open-label, multicentre, adaptive randomised controlled trial) found that CPAP reduced the need for invasive mechanical ventilation in adults admitted to hospital with acute respiratory failure. Neither CPAP nor HFNO reduced mortality when compared with conventional oxygen therapy.[732]
The HELMET-COVID trial (a multicentre randomised clinical trial) found that helmet non-invasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support (alternate use of mask non-invasive ventilation, HFNO, or standard oxygen according to clinical response) among patients with acute hypoxaemic respiratory failure. However, there were several important limitations to the study, and interpretation of the findings is limited by imprecision in the effect size estimate.[733]
The SOHO-COVID trial (a randomised clinical trial) found that HFNO did not significantly reduce 28-day mortality compared with standard oxygen therapy among patients with respiratory failure.[734] However, another randomised controlled trial found that treatment with HFNO reduced the likelihood of invasive mechanical ventilation and decreased the time to clinical recovery compared with conventional low-flow oxygen therapy in patients with severe disease.[735]

Oxygen therapy in your patient with asthma

If your patient’s asthma is stable, follow guideline recommendations for oxygen saturation target for the presenting acute condition (i.e., COVID-19).[1263]

Measure resting oxygen saturation in all patients with asthma with any acute illness.[1263] This is routine practice in patients with COVID-19.

The Global Initiative for Asthma recommends controlled oxygen to maintain saturations between 93% and 95% for an acute asthma exacerbation.[1178]
Be aware that pulse oximetry may overestimate oxygen saturation in patients with darker skin tones.[1178]
Hypercapnia in asthma is a near fatal sign showing a patient is tiring and needs ventilatory support.[1196] Intensive care support is needed immediately.[1196]

Oxygen therapy in your patient with COPD

If your patient with comorbid COPD is suitable for full escalation of care refer for consideration of ventilation support if they are:

Severely hypoxaemic (PaO₂ <7.3 kPa [<54.8 mmHg]) despite oxygen therapy (based on expert opinion)
Hypercapnic (PaCO₂ >6 kPa [>45 mmHg]) with respiratory acidosis (pH <7.35)[1263]
AND/OR
Exhibiting changes in mental status (confusion, coma).

Follow the guidance on oxygen as below
Discuss with your senior or respiratory expert whether ward-based non-invasive ventilation is suitable.

Practical tip

Measure resting oxygen saturations and be aware of additional factors to consider when prescribing oxygen therapy in a patient with COPD who is hypoxic.

Guidelines on emergency oxygen use (not specifically for COVID-19) from the British Thoracic Society recommend that any patient with COPD requiring oxygen supplementation needs an arterial blood gas (ABG) measurement.[1263]
Re-check ABG after 30 to 60 minutes in all patients.[1263]

If a patient with comorbid COPD is critically ill (e.g., shock, sepsis) and needs high levels of oxygen:

The British Thoracic Society (BTS) guideline on emergency oxygen use (not specifically for COVID-19) recommends an initial target oxygen saturation in line with the recommendation for patients without COPD.[1263] Evidence suggests that targeting an upper oxygen saturation level of 96% may be preferred compared with a higher level.[1264][1265] Follow your local hospital protocol on target oxygen saturations recommended in your hospital during the COVID-19 pandemic for acutely ill patients
Subsequently, you may need to adjust to controlled oxygen therapy with a target oxygen saturation range of 88% to 92% depending on the ABG results.[1263]

Use an initial target oxygen saturation of 88% to 92%
Check ABG and recheck after 30 to 60 minutes.

If a patient with comorbid COPD is acutely but not critically ill and is NOT at risk of hypercapnic respiratory failure (e.g., stable, mild COPD with minimal symptoms):

Use an initial target oxygen saturation as recommended by guidelines for the presenting acute condition.
- Evidence suggests that for most acutely ill patients targeting an upper oxygen saturation level of 96% may be preferred compared with a higher level.[1264][1265] This target saturation level may be lower depending on local hospital oxygen supplies (follow your local protocol)
Measure ABG as soon as possible[1263]
Subsequently, you may need to adjust to controlled oxygen therapy with a target oxygen saturation range of 88% to 92% depending on the ABG results.[1263]

Consider – invasive mechanical ventilation

Back

Consider –

invasive mechanical ventilation

Additional treatment recommended for SOME patients in selected patient group

Consider endotracheal intubation and mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) who are acutely deteriorating despite advanced oxygen/non-invasive ventilatory support measures.[85]

Use of mechanical ventilation in COVID-19 patients carries a high risk of mortality. Mortality is highly variable across studies, ranging between 21% and 100%. An overall in-hospital mortality risk ratio of 0.70 has been reported based on random-effect pooled estimates. Outcomes appear to have improved as the pandemic has progressed.[739] However, results have not been consistent.[740]
Early intubation may be associated with lower all-cause mortality compared with patients undergoing late intubation. However, again, results have not been consistent.[741][742]
Endotracheal intubation should be performed by an experienced provider using airborne precautions.[85]
Young children, or adults who are obese or pregnant, may desaturate quickly during intubation and therefore require pre-oxygenation with 100% fraction of inspired oxygen (FiO₂) for 5 minutes.[85]

Mechanically ventilated patients with ARDS should receive a lung-protective, low tidal volume/low inspiratory pressure ventilation strategy (lower targets are recommended in children).

A higher positive end-expiratory pressure (PEEP) strategy is suggested over a lower PEEP strategy in moderate to severe ARDS. However, individualisation of PEEP, where the patient is monitored for beneficial or harmful effects and driving pressure during titration with consideration of the risks and benefits of PEEP titration, is recommended.[85][696]
Although some patients with COVID-19 pneumonia meet the criteria for ARDS, there has been some discussion about whether COVID-19 pneumonia is its own specific disease with atypical phenotypes. Anecdotal evidence from early in the pandemic suggested that the main characteristic of the atypical presentation was the dissociation between well-preserved lung mechanics and the severity of hypoxaemia.[743][744][745][746][747][748] However, this hypothesis was criticised.[749][750] A systematic review and meta-analysis published in late 2022 found no evidence for distinct respiratory system static compliance-based clinical phenotypes in patients with COVID-19-related ARDS.[751]
It has been argued that an evidence-based approach extrapolating data from ARDS not related to COVID-19 is the most reasonable approach for intensive care of COVID-19 patients.[752] However, some clinicians have warned that protocol-driven ventilator use may cause lung injury in some patients, and that ventilator settings should be based on physiological findings rather than using standard protocols. High PEEP may have a detrimental effect on patients with normal compliance.[743] Therefore, PEEP should always be carefully titrated.[753]

Consider prone ventilation in patients with severe ARDS for 12 to 16 hours per day.

Pregnant women in the third trimester may benefit from being placed in the lateral decubitus position. Caution is required in children.[85][696]
Longer durations may be feasible in some patients.[754]
Lung recruitment manoeuvres are suggested, but staircase recruitment manoeuvres are not recommended.[696]
A systematic review and meta-analysis found that there was no significant difference in mortality between prone and supine positioning, and that hospital stay was significantly higher in the prone position group. There was no difference between the two groups in terms of length of stay in the intensive care unit and days of mechanical ventilation.[755]

Consider – inhaled pulmonary vasodilator

Consider – extracorporeal membrane oxygenation (ECMO)

Back

Consider –

extracorporeal membrane oxygenation (ECMO)

Additional treatment recommended for SOME patients in selected patient group

Consider ECMO according to availability and expertise if the above methods fail.[85][696]

Evidence to support the use of ECMO is limited.

A registry-based cohort study found that ECMO was associated with a 7.1% reduction in mortality in selected adults (i.e., PaO₂/FiO₂ <80 mmHg) with COVID-19-associated respiratory failure, compared with conventional mechanical ventilation without ECMO. It was most effective in patients aged <65 years and those with a PaO₂/FiO₂ <80 mmHg or with driving pressures >15 cm H₂O during the first 10 days of mechanical ventilation.[757]
Pooled mortality rates in adults receiving ECMO ranged from 39% to 49%.[758][759] The mortality rate in children was 26.6%.[760] Factors associated with an increased risk of mortality included older age, male sex, chronic lung disease, longer duration of symptoms, longer duration of invasive mechanical ventilation, higher driving pressure, and higher partial pressure of arterial carbon dioxide.[761]
There is a high risk of thrombotic and neurological complications (e.g., circuit thrombosis, major bleeding, intracranial haemorrhage, ischaemic stroke, and hypoxic ischaemic brain injury) in patients on ECMO.[762][763][764]

Consider – corticosteroid

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Consider –

corticosteroid

Additional treatment recommended for SOME patients in selected patient group

Consider a systemic corticosteroid. Guideline recommendations vary.

The World Health Organization strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with critical disease. This recommendation is based on moderate-quality evidence that suggests systemic corticosteroids probably reduce 28-day mortality in patients with critical disease. They also probably reduce the need for invasive ventilation. There is no evidence directly comparing dexamethasone and hydrocortisone. The harms of treatment in this context are considered to be minor. It is unclear whether these recommendations can be applied to children or those who are immunocompromised.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends offering dexamethasone (or an alternative such as hydrocortisone or prednisolone when dexamethasone cannot be used or is unavailable) to people who need supplemental oxygen to meet their prescribed oxygen saturation levels, or who have a level of hypoxia that needs supplemental oxygen but who are unable to have or tolerate it. Treatment is for up to 10 days unless there is a clear indication to stop early.[401]
In the US, the Infectious Diseases Society of America recommends dexamethasone (or an alternative corticosteroid if dexamethasone is not available) for 10 days or until hospital discharge in critically ill patients.[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Evidence supports the use of corticosteroids in hospitalised patients.

A Cochrane review found that systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in hospitalised patients with symptomatic disease, although the evidence is very uncertain about the effect on all-cause mortality up to 120 days. Evidence related to the most effective type, dose, or timing of corticosteroid is uncertain.[709]
Evidence suggests that higher doses may be superior to lower doses in reducing mortality in patients with severe or critical disease.[712] However, the RECOVERY trial continues to assess higher doses in hospitalised patients who require non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).[713]
Evidence also suggests that shorter treatment courses may optimise the mortality benefit in hospitalised patients. An optimal duration of treatment was <7 days in one meta-analysis, with no additional survival benefit reported with ≥7 days of treatment.[714]

Monitor patients for adverse effects (e.g., hyperglycaemia, secondary infections, psychiatric effects, reactivation of latent infections) and assess for drug-drug interactions.

Manage your patient’s diabetes when they are taking corticosteroids

Giving corticosteroids to someone with diabetes will worsen their glycaemic control, so test blood glucose at least four times a day.[1269]

For patients with diabetes, use the same doses of corticosteroid as for patients without diabetes but adjust diabetes medication, as their diabetes control will get worse.
Synthetic corticosteroids can cause hyperglycaemia by affecting carbohydrate metabolism and inducing insulin resistance.[1270]
COVID-19 is also associated with increased insulin resistance as well as reduced insulin secretion from the pancreatic beta cells.[1269]
If hyperglycaemia does occur, rule out diabetic ketoacidosis or hyperosmolar hyperglycaemic state and follow your hospital protocol on managing blood glucose in patients with diabetes and COVID-19 taking corticosteroids.[1269]
- The recommended protocol by the UK-based National Inpatient Diabetes COVID-19 Response Group for the ward setting uses subcutaneous insulin.[1269]
- The group highlights that sulfonylureas are not recommended in this scenario due to potential impairment of beta cell function and likely severe insulin resistance.[1269]

When you stop the corticosteroid dose, glycaemic control will likely improve, although this may occur over a few days.

Follow your local protocol on titrating antidiabetic medication.

Monitor for psychiatric complications of corticosteroids

Check previous response to corticosteroids.

Although all patients should be monitored for adverse effects, the risk of depression, mania, panic disorder, or suicide during corticosteroid therapy has been reported to be higher in people who are already living with these conditions, but not consistently so.[1271]
Consider referral for psychiatric advice on whether to offer prophylactic medication.[1271]

Monitor for psychiatric adverse effects.

These may vary in severity and include among others:[1272]
- Anxiety and insomnia
- Severe mood changes, including manic states
- Cognitive impairment.
Effects seem to be dose-related and are more common with long-term regimens or long-acting formulations, and in older patients.[1271] This also stands true for patients who have neuropsychiatric adverse effects related to discontinuing long-term corticosteroid therapy.[1273]
Manic episodes and delirious states are the most common psychiatric adverse effects when starting corticosteroid treatment, whereas depression is most common during chronic therapy.[1271][1274]
Be mindful of a possible withdrawal reaction, which may present with weakness, fatigue, gastrointestinal symptoms, and delirium, as well as with psychiatric complications such as depression, when discontinuing corticosteroids.[1273]

If your patient develops psychiatric complications related to corticosteroids, liaise with the psychiatry team for advice on appropriate management (based on expert opinion).

This may include adjusting dose or earlier discontinuation of the corticosteroid therapy if the clinical situation allows.[1271]

Primary options

dexamethasone: children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone : children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone: children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days

hydrocortisone sodium succinate: children: consult specialist for guidance on dose; adults: 50 mg intravenously every 8 hours for 7-10 days

hydrocortisone sodium succinate : children: consult specialist for guidance on dose; adults: 50 mg intravenously every 8 hours for 7-10 days

hydrocortisone sodium succinate: children: consult specialist for guidance on dose; adults: 50 mg intravenously every 8 hours for 7-10 days

Secondary options

prednisolone: children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone : children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone: children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

methylprednisolone: children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 2-4 divided doses for 7-10 days

methylprednisolone : children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 2-4 divided doses for 7-10 days

methylprednisolone: children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 2-4 divided doses for 7-10 days

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

dexamethasone

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

hydrocortisone sodium succinate

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Secondary options

prednisolone

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

methylprednisolone

For patients with CKD, please check your local drug formulary

For patients with CKD see dose in the Renal Drug HandbookFor patients with CKD see dose in the Renal Drug Handbook

Consider – interleukin-6 (IL-6) inhibitor

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Consider –

interleukin-6 (IL-6) inhibitor

Additional treatment recommended for SOME patients in selected patient group

Consider an IL-6 inhibitor. Guideline recommendations vary.

The World Health Organization strongly recommends a single dose of an IL-6 inhibitor (tocilizumab or sarilumab) in adults with critical disease. IL-6 inhibitors may be administered in combination with corticosteroids and Janus kinase inhibitors, and should be initiated at the same time as systemic corticosteroids. This recommendation is based on high-certainty evidence that shows IL-6 inhibitors reduce mortality and the need for mechanical ventilation, and low-certainty evidence that suggests that IL-6 inhibitors may also reduce the duration of mechanical ventilation and hospitalisation. The evidence regarding the risk of severe adverse events is uncertain. The applicability of this recommendation to children is currently uncertain.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends a single dose of tocilizumab in hospitalised adults who are having systemic corticosteroids and need supplemental oxygen or mechanical ventilation.[401][664]
In the US, the Infectious Diseases Society of America recommends a single dose of tocilizumab (or sarilumab if tocilizumab is not available) in critically ill patients who have elevated markers of systemic inflammation in addition to standard care (i.e., corticosteroids).[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Evidence supports the use of IL-6 inhibitors.

A Cochrane review found that tocilizumab reduced all-cause mortality at day 28 (high-certainty evidence) compared with standard care alone or placebo. The evidence suggests uncertainty around the effect of tocilizumab on mortality after day 60. Evidence for an effect on these outcomes for sarilumab is very uncertain. Tocilizumab and sarilumab probably result in little or no increase in clinical improvement at day 28 (i.e., hospital discharge or improvement measured by triallist-defined scales) (moderate-certainty evidence). The evidence for clinical improvement after day 60 is very uncertain for both drugs.[718]
A living systematic review and network meta-analysis found that IL-6 inhibitors (with corticosteroids) probably reduce mortality (moderate-certainty evidence), are likely to reduce the need for mechanical ventilation (moderate-certainty evidence), and may reduce the duration of hospitalisation (moderate-certainty evidence) compared with standard care.[710][711]
IL-6 inhibitors may not be beneficial when used alone (without corticosteroids).[719]

Patients on IL-6 inhibitors are at increased risk of infection including active tuberculosis, invasive fungal infections, and opportunistic pathogens.

Routine blood work including neutrophil count, platelets, transaminases, and total bilirubin should be checked prior to initiation of therapy. All patients should be monitored for signs and symptoms of infection given the increased risk of immunosuppression in addition to systemic corticosteroids.[402]

Primary options

tocilizumab: children: consult specialist for guidance on dose; adults: 8 mg/kg intravenously as a single dose, maximum 800 mg/dose

tocilizumab : children: consult specialist for guidance on dose; adults: 8 mg/kg intravenously as a single dose, maximum 800 mg/dose

tocilizumab: children: consult specialist for guidance on dose; adults: 8 mg/kg intravenously as a single dose, maximum 800 mg/dose

sarilumab: adults: 400 mg intravenously as a single dose

sarilumab : adults: 400 mg intravenously as a single dose

sarilumab: adults: 400 mg intravenously as a single dose

Consider – Janus kinase (JAK) inhibitor

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Consider –

Janus kinase (JAK) inhibitor

Additional treatment recommended for SOME patients in selected patient group

Consider a JAK inhibitor. Guideline recommendations vary.

The World Health Organization strongly recommends an oral JAK inhibitor (baricitinib) for 14 days or until hospital discharge (whichever is first) in adults with critical disease. Baricitinib may be administered in combination with corticosteroids and IL-6 inhibitors, and should be initiated at the same time as systemic corticosteroids. This recommendation is based on high-certainty evidence that baricitinib reduces mortality, and moderate-certainty evidence that baricitinib probably reduces the duration of mechanical ventilation and the length of hospital stay. The applicability of this recommendation to children is currently uncertain.[402][654][655]
In the UK, the National Institute for Health and Care Excellence recommends baricitinib in hospitalised adults who: need supplemental oxygen, and are having or have completed a course of corticosteroids (unless contraindicated), and have no evidence of infection (other than SARS-CoV-2) that might be worsened by baricitinib. It may also be considered in children ≥2 years of age provided they meet the same criteria.[401]
In the US, the Infectious Diseases Society of America recommends baricitinib in critically ill patients receiving HFNO or non-invasive ventilation (and patients receiving invasive ventilation or ECMO when IL-6 inhibitors are not available), in addition to corticosteroid therapy.[398]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Other drugs in this class include tofacitinib and ruxolitinib.

The World Health Organization recommends against using other drugs in this class unless baricitinib or IL-6 inhibitors are not available. The effects of tofacitinib or ruxolitinib on mortality, need for mechanical ventilation, and hospital length of stay remain uncertain and more trial evidence is needed.[402][654][655]

Evidence supports the use of JAK inhibitors.

A Cochrane review found that JAK inhibitors probably reduced all-cause mortality up to day 28 (moderate-certainty evidence) and up to day 60 (high-certainty evidence). They probably make little or no difference in improvement in clinical status or the rate of adverse events (moderate-certainty evidence). Baricitinib was the most often evaluated JAK inhibitor.[720]
A living systematic review and network meta-analysis found that JAK inhibitors probably reduce mortality (high-certainty evidence), reduce the duration of mechanical ventilation (high-certainty evidence), and reduce length of hospital stay (high-certainty evidence) compared with standard care.[710][711]

Patients are at increased risk of infection including active tuberculosis, invasive fungal infections, and opportunistic pathogens.[402]

Avoid use in patients with known active tuberculosis.
All patients should be monitored for signs and symptoms of infection given the increased risk of immunosuppression in addition to systemic corticosteroids.
Monitor full blood count with differential before and during treatment.

Baricitinib is not recommended in patients with severe renal or hepatic impairment.[402]

Baricitinib is not recommended in adults with an estimated glomerular filtration rate ≤15 mL/minute (≤30 mL/minute in children <9 years of age), or in patients on dialysis or renal replacement therapy. A dose reduction is recommended in patients with an estimated glomerular filtration rate ≤60 mL/minute.
Baricitinib has not been studied in patients with severe hepatic impairment and it is unknown whether a dose adjustment is required in these patients. It should only be used if the potential benefits outweigh the potential risks.
Use caution with tofacitinib and ruxolitinib in patients with moderate to severe renal impairment (including those on dialysis); a dose adjustment may be required.
Monitor renal and hepatic function before and during treatment.

Adverse effects include leukopenia, lymphopenia, thrombocytosis, anaemia, blood clotting abnormalities, hepatic impairment, and secondary infection.[402]

Other serious adverse effects include venous thrombosis and severe infections.

Take your patient’s risk of adverse effects into account when considering a JAK inhibitor

Check kidney function before starting a JAK inhibitor in your patient with CKD.

Check your local formulary as dose adjustments may be needed.
Baricitinib is not recommended if your patient is on dialysis, has end-stage kidney failure, or has acute kidney injury.[1193]
Ruxolitinib and tofacitinib should be used with caution in moderate to severe renal impairment and a dose adjustment may be required. Consult your local formulary and seek advice from the nephrology team.

Monitor kidney function particularly closely during JAK inhibitor treatment in your patient with CKD.

Primary options

baricitinib: children: consult specialist for guidance on dose; adults: 4 mg orally once daily for 14 days

baricitinib : children: consult specialist for guidance on dose; adults: 4 mg orally once daily for 14 days

baricitinib: children: consult specialist for guidance on dose; adults: 4 mg orally once daily for 14 days

Secondary options

tofacitinib: children and adults: consult specialist for guidance on dose

tofacitinib : children and adults: consult specialist for guidance on dose

tofacitinib: children and adults: consult specialist for guidance on dose

ruxolitinib: children and adults: consult specialist for guidance on dose

ruxolitinib : children and adults: consult specialist for guidance on dose

ruxolitinib: children and adults: consult specialist for guidance on dose

Plus – continue your patient's inhalers as prescribed for asthma or COPD if appropriate

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Plus –

continue your patient's inhalers as prescribed for asthma or COPD if appropriate

Treatment recommended for ALL patients in selected patient group

Patients with an acute medical condition can forget to tell you about their inhalers prescribed for COPD or asthma. Remember to check and prescribe if appropriate.

Many inhalers contain a combination of medications, so ensure no dual prescribing.
Patients with COPD or asthma who develop acute kidney injury with an estimated GFR <50 mL/minute/1.73 m² may need to temporarily stop their usual inhaled long-acting muscarinic antagonist, depending on which specific drug is used.
- Check local formulary or seek pharmacist advice.

Other prescribed medication

Patients with severe asthma or COPD who take oral corticosteroids as regular prescribed maintenance therapy should also continue to take these at the lowest dose possible, as their condition may deteriorate if these are stopped.[1178][1195]
Patients who take biological therapy for severe asthma should continue to take this treatment, unless specifically advised not to do so.[1178]

Plus – weigh up risks versus benefits of prescribed antihypertensive medication

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Plus –

weigh up risks versus benefits of prescribed antihypertensive medication

Treatment recommended for ALL patients in selected patient group

Despite initial concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, high-certainty evidence has found that the use of these drugs is not associated with severe disease or poor outcomes.[1198][1199][1200]

Do an individual clinical assessment
Consider the original indication for any RAAS inhibitors (ACE inhibitors, angiotensin-II receptor antagonists, mineralocorticoid receptor/aldosterone antagonists) and degree of prognostic benefit
If medication is temporarily withheld, consider when to re-introduce again once health improves.

Seek advice from the patient’s cardiology or nephrology team if they have complex conditions (e.g., on renal replacement therapy or immunosuppressive therapy).

Plus – review current treatment for depression

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Plus –

review current treatment for depression

Treatment recommended for ALL patients in selected patient group

Ask your patient which medications they are taking for their mental health. Alternatively, review their primary care records for relevant information (if available).

Drug-drug interactions and their associated adverse effects of particular relevance to patients with COVID-19 include sedation, cardiotoxicity (QT prolongation), and respiratory depression.[1159]

Consider that antidepressants may be used in the treatment of conditions other than depression, and drugs other than antidepressants may be used to treat depression.

Prescribe the patient’s usual antidepressant medication, unless there are good reasons not to (based on expert opinion).

If antidepressants are stopped abruptly, the patient may develop discontinuation symptoms.[1235]
The severity of symptoms of discontinuation may vary, but it may be unpleasant and may complicate the management of the acute medical condition.[1235][1236]

When reviewing current medication, look out for:

Current and previous adverse effects
Recent changes in dose
Recent switches from a different class of medication
Pharmacological nuances of specific depression subtypes (e.g., it is likely that patients suffering from psychotic depression would be co-prescribed an antipsychotic)
Augmenting strategies that may be in use when treating resistant depression (e.g., lithium or quetiapine augmentation of a selective serotonin-reuptake inhibitor [SSRI]).

Consider drug-drug interactions.

Antidepressant medications may cause pharmacokinetic (by inhibiting the CYP450 pathway) and pharmacodynamic interactions with medications used for other conditions.[1237][1238] Consider this issue for all medications prescribed in patients with COVID-19 as well as any experimental therapies (see the Emerging section).

Consider psychiatric complications when prescribing non-psychotropic drugs.

Take particular care when prescribing corticosteroids, anticonvulsants, and antiparkinsonian medication.

Consider adverse effects, which may include the following.[1238]

QT prolongation, arrhythmias, increased heart rate, or postural hypotension with tricyclic antidepressants. Check ECG, especially in people at risk of arrhythmias.
Hyponatraemia, caused by antidepressants, especially SSRIs, and compounded by other co-prescribed drugs (e.g., diuretics). Check your patient’s serum electrolytes.
Serotonin syndrome (altered mental state, agitation, tremor, hyper-reflexia, clonus, muscle rigidity, diaphoresis, tachycardia, increased bowel sounds, temperature >38℃), especially with polypharmacy and/or overdose of a serotonergic agent.[1239][1240] See Serotonin syndrome.
- Be particularly aware of increased risk of serotonin syndrome in patients with end-stage renal disease on SSRIs. Treating depression in patients with renal impairment requires a multidisciplinary approach and demands extra caution.
Hepatotoxicity. Adjust doses of antidepressants in patients with hepatic impairment if necessary and avoid drugs that are known to be hepatotoxic.
Gastrointestinal bleeding. SSRIs are associated with an increased risk of gastrointestinal bleeding.[1238] Risk is particularly increased when co-prescribed with aspirin, non-steroidal anti-inflammatory drugs, or oral anticoagulants.[1241][1242] Try to avoid this combination of drugs.[1238] Monitor closely and consider gastroprotection with proton-pump inhibitors if SSRI use cannot be avoided.[1238]

Ask your patient about non-pharmacological treatments for their depression and check the current level of support in the community.

This may include other health professionals involved in their care, charities, family and social networks, and psychological therapy.

Practical tip

Consider – plan for discharge and rehabilitation

Consider – palliative care

Plus – monitor comorbidities during hospital stay

Back

Plus –

monitor comorbidities during hospital stay

– ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

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–

ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

Treatment recommended for ALL patients in selected patient group

Monitor for acute worsening of respiratory symptoms and be aware that this may suggest a patient with comorbid asthma is having an acute exacerbation of their asthma.

Seek senior advice.
Follow standard guideline recommendations on assessing severity and managing an acute exacerbation of asthma in adults, even if COVID-19 is suspected as the trigger.[1196]
- See Acute asthma exacerbation in adults.
- Avoid using a nebuliser where possible. Consider whether it may be clinically appropriate to use a metered-dose inhaler delivered via a spacer device with a mouthpiece or tightly fitted face mask as an alternative delivery mechanism to a nebuliser.[1178] Follow your local protocols.
Start oral corticosteroids as clinically indicated for asthma exacerbations.[1178][1196]
Consider temporarily stopping any long-acting muscarinic antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a short-acting muscarinic antagonist (e.g., ipratropium) (based on expert opinion).
- This is due to concern over possible additive anticholinergic adverse effects.
- Ensure to re-prescribe the LAMA once the nebuliser treatment has been stopped.

– ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

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–

ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

Treatment recommended for ALL patients in selected patient group

If an exacerbation of COPD is suspected in a patient with COVID-19 and pre-existing COPD:

Seek senior or specialist advice.
Differentiate from other conditions, such as acute coronary syndrome, acute heart failure, and pneumonia, as well as from complications of COVID-19.[1195]
Follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[1195] See Acute exacerbation of COPD.
Consider using pressurised metered-dose inhalers, dry powder inhalers, or soft mist inhalers for drug delivery instead of nebulisers in non-critically ill patients not receiving ventilatory support.[1195] Follow your local guidance and protocols.
The Global Initiative for Chronic Obstructive Disease recommends continuing inhaled long-acting bronchodilators during an exacerbation, or starting them as soon as possible before discharge from hospital.[1195] This is an individualised clinical decision due to limited evidence.
Consider temporarily stoping any long-acting muscarinic antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a short-acting muscarinic antagonist (e.g., ipratropium) (based on expert opinion).
- This is due to concern over possible additive anticholinergic adverse effects.
- Ensure the LAMA is re-prescribed once the nebuliser treatment has been stopped.

– monitor and manage blood glucose during the hospital admission

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–

monitor and manage blood glucose during the hospital admission

Treatment recommended for ALL patients in selected patient group

Monitor blood glucose levels at least four times a day (every 4-6 hours or, if eating, pre-meal and before bedtime) in any acutely ill patient with diabetes mellitus.[1226]

Follow your local protocol on blood glucose monitoring for inpatients with COVID-19 who have diabetes.

Hyperglycaemia during the ongoing hospital admission

Act promptly to treat hyperglycaemia to avoid diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS), which are medical emergencies.

Follow your local hospital protocol if your patient’s capillary blood glucose is ≥12 mmol/L (≥216 mg/dL).
- COVID-19 guidance generally emphasises the importance of managing hyperglycaemia.[1185]
- Exclude DKA or HHS, both of which require specific urgent management.
- Consider other conditions associated with hyperglycaemia, such as sepsis.[1184]
Be aware that the following medications may be associated with hyperglycaemia and may need to be reviewed:[1228]
- Corticosteroids (e.g., dexamethasone)
- Some beta-blockers (e.g., propranolol, atenolol)
- Thiazide diuretics (e.g., hydrochlorothiazide)
- Some second-generation antipsychotics (e.g., olanzapine, clozapine)
- Certain fluoroquinolone antibiotics (e.g., ciprofloxacin)
- Calcineurin inhibitors (e.g., ciclosporin, tacrolimus)
- Protease inhibitors (e.g., ritonavir).
If your patient does not have DKA/HHS but has a blood glucose above 12 mmol/L (216 mg/dL), follow your local protocols on management of hyperglycaemia in patients with COVID-19.[1227]
- Be aware that patients with type 2 diabetes in ICU may have significant degrees of insulin resistance. Seek support from your diabetes specialist inpatient team in these circumstances.[1227]

Practical tip

Ask for expert advice from the inpatient diabetes team.

Hypoglycaemia during the ongoing hospital admission

Monitor blood glucose and adjust medication in response to illness and hospital meal times, to reduce the risk of hypoglycaemic episodes.

Approximately 1 in 5 inpatients with diabetes in England and Wales were found to have had a hypoglycaemic episode during their hospital stay.[1229]

Causes of hypoglycaemia include:[1230]

Recovery from an acute illness
- Patients recovering from COVID-19 may have a rapid change in insulin requirements, so monitor and adjust insulin regimens carefully[1227]
Accidental interruptions to patient feeding, which may occur especially when patients with COVID-19 are nursed in the prone position[1184]
Reducing doses of corticosteroids, particularly dexamethasone in patients with COVID-19[1227]
Insulin or oral hypoglycaemic medication error
Wrong timing of insulin in relation to meals
Patients eating less but taking the same amount of diabetes medication
No bedtime snacks
Reduced appetite or vomiting.

In the acute hospital setting, meal times may be interrupted or may not always be at exactly the same time each day.
- Give sulfonylurea medication before or with food. Check local drug formulary for more specific guidance on timing of dose in relation to food for specific sulfonylurea.
- Never give sulfonylurea medication at bedtime and, if the patient is taking a dose with their evening meal, consider reducing the evening dose to reduce the risk of nocturnal hypoglycaemia (based on expert opinion).

Practical tip

Bedtime snacks can reduce the risk of early morning hypoglycaemia.[1229]

Consider intervening if the blood glucose falls below 6 mmol/L (108 mg/dL) (‘looming/impending’ hypoglycaemia) if on insulin or on sulfonylureas.

These patients are at high risk of progressing to hypoglycaemia.
Give carbohydrates as recommended in the hypoglycaemia guideline and follow your local protocol.[1230]

Retest blood glucose at 10 to 15 minutes to determine response to treatment
Never stop the next scheduled dose of insulin if the hypoglycaemia has been corrected. This can cause rebound hyperglycaemia and DKA in people with type 1 diabetes.
- Seek diabetes inpatient specialist team advice on whether a review of your patient’s insulin regimen is needed.

Follow local protocols and guidance on self-monitoring of blood glucose by patients in hospital.

These may have been adapted in the context of patients with COVID-19. For instance, some hospitals in the US have been utilising ‘virtual’ formats, including expanding self-management protocols, to reduce need for personal protective equipment, where it is safe to do so.[1185]

– check your patient’s feet

– mental state examination

– consider referral to the liaison psychiatry team

Back

–

consider referral to the liaison psychiatry team

Treatment recommended for ALL patients in selected patient group

Consider a referral to the liaison psychiatry team/service for any patient with established or suspected depression who is admitted to hospital with an acute condition.[1246][1247]

Referral may not be required if there are no concerns that depression and/or its management (e.g., medication) may be impacting on the acute condition (based on expert opinion).
Follow your local protocols/referral pathways in your hospital.
COVID-19 is associated with psychiatric and neurological manifestations including depression.[1159]

Evidence: Depression and adherence to treatment post-discharge

Comorbid depression is linked to poor adherence with recommended physical health treatments, from medication to rehabilitation.[1248]

This may lead to worse clinical outcomes, including higher readmission risk.[1249][1250][1251]
Most importantly, affective symptoms including depression have been linked with excess mortality, though a causal link remains to be proven.[1252][1253]

– manage nicotine dependence and support current smokers to stop smoking

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–

manage nicotine dependence and support current smokers to stop smoking

Treatment recommended for ALL patients in selected patient group

Evidence suggests there is an association with increased severity of COVID-19 and risk of death in hospitalised patients who smoke tobacco.

In light of this, in addition to the well-recognised harms, the World Health Organization recommends smoking cessation using evidence-based methods.[1255]

Offer nicotine replacement therapy (NRT) and other smoking cessation pharmacotherapies for all inpatients who smoke if there are no contraindications.[1254]

Advise that:[1254]

Nicotine is highly addictive but is not the cause of smoking-related harms
NRT prevents rapid withdrawal during admission, which can be distressing and uncomfortable
There are several highly effective treatment options that offer the best chance of stopping smoking when combined with specialist support.

Ask about the time to first cigarette after waking. An answer of <30 minutes can indicate which patients may have more problems with nicotine dependence and can guide choice on dosing for transdermal nicotine patch.
Check your local formulary for any precautions, particularly if your patient has one or more comorbidity and/or is haemodynamically unstable.
Ensure a sufficient dose of NRT is prescribed to adequately address withdrawal symptoms.[1258]

Check local formulary for a full list of contraindications/cautions or seek pharmacist advice.
Mental health illness is NOT a contraindication to prescribing varenicline. However, varenicline should be used with caution in people with a pre-existing psychiatric illness as it may worsen symptoms.
Bupropion is an alternative option for smoking cessation but is less likely to result in successful quitting.[1254][1261] Consider the potential for drug-drug interactions.

Use of this content is subject to our disclaimer

Coronavirus disease 2019 (COVID-19)

Treatment algorithm

mild to moderate (non-severe) disease

consider home management or hospital admission

Be aware of any comorbidity-associated risk for clinical deterioration and severe disease

Assess your patient’s level of frailty

Practical tip

set an escalation plan/consider ceiling of intervention

monitoring

Check baseline kidney function and monitor closely

symptom management and supportive care

Support your patient with known depression

antipyretic/analgesic

NSAIDs in your patient with chronic kidney disease, heart failure, or asthma

Chronic kidney disease (CKD)

Heart failure

Asthma

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

if your patient is not admitted to hospital, advise them on self-management of their diabetes

Practical tip

Key general points for all patients with diabetes

Practical tip

People with type 1 diabetes

People with type 2 diabetes

Practical tip

review diabetes medication on admission to hospital (NEVER stop insulin in a person with type 1 diabetes)

Practical tip

Practical tip

antimicrobials

antiviral

Take your patient’s medications and comorbidities into account when considering antiviral therapy

Comorbidities and risk of admission to hospital

Drug interactions

Asthma or COPD

CKD

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

monoclonal antibody

continue your patient's inhalers as prescribed for asthma or COPD if appropriate

if your patient is not admitted to hospital, ensure plans are in place in case of any asthma exacerbation

if your patient is not admitted to hospital, ensure plans are in place to manage any COPD exacerbation

weigh up risks versus benefits of prescribed antihypertensive medication

Plus – monitor comorbidities during hospital stay

monitor comorbidities during hospital stay

baseline neurological assessment

baseline cognitive and delirium assessments with collateral history

Delirium

More info: Investigations

Management of a patient with delirium in hospital and long-term care

Evidence: Risks and safe withdrawal of antipsychotics in older people

ensure monitoring is in place to detect any asthma exacerbation during your patient's hospital admission

ensure monitoring is in place to detect any COPD exacerbation during your patient's hospital admission

monitor and manage blood glucose during the hospital admission

Hyperglycaemia during the ongoing hospital admission

Practical tip

Hypoglycaemia during the ongoing hospital admission

Practical tip

check your patient’s feet

mental state examination

review current treatment for depression

Practical tip

consider referral to the liaison psychiatry team

Evidence: Depression and adherence to treatment post-discharge

manage nicotine dependence and support current smokers to stop smoking

severe disease

hospital admission

Assess your patient’s level of frailty

Practical tip

Baseline neurological assessment

set an escalation plan/consider ceiling of intervention