BMJ Best Practice

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

omorbiditiesomorbidities:

ACUTE

mild COVID-19

1st line – consider home isolation

Patients with suspected or confirmed mild disease (i.e., symptomatic patients meeting the case definition for COVID-19 without evidence of hypoxia or pneumonia) and asymptomatic patients should be isolated to contain virus transmission.[2]

Manage patients in a healthcare facility, in a community facility, or at home. Home isolation can be considered in most patients, with telemedicine or remote visits as appropriate.[2][3]This decision requires careful clinical judgement and should be informed by an assessment of the patient’s home environment to ensure that: infection prevention and control measures and other requirements can be met (e.g., basic hygiene, adequate ventilation); the carer is able to provide care and recognise when the patient may be deteriorating; the carer has adequate support (e.g., food, supplies, psychological support); the support of a trained health worker is available in the community.[478]The location of care will depend on guidance from local health authorities and available resources.

Pregnant women with suspected or confirmed mild disease may not require acute care in a hospital unless there is concern for rapid deterioration or an inability to return to hospital promptly.[2]

Comorbidities in pregnancy and in children

The information in the BMJ Best Practice comorbidities tool relates to non-pregnant adults.

It is not intended for pregnant patients or for children. In these circumstances, please seek specialist obstetric/gynaecology or paediatric advice on how any comorbidities the patient has may affect your management of COVID-19.

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

Consider the presence of any comorbidities when deciding the setting for care and levels of monitoring.

The US Centers for Disease Control and Prevention's list of pre-existing conditions that do, or may increase the risk of severe illness with COVID-19 includes:[157]

Chronic kidney disease
COPD
Coronary artery disease
Heart failure
Type 1 and type 2 diabetes
Asthma (moderate to severe)
Stroke
Hypertension
Dementia.

Data on comorbidity-related risk continue to emerge. A large cohort study in England found that mortality risk was higher in people with type 1 compared with type 2 diabetes, when risk was adjusted for demographic factors and cardiovascular comorbidities.[194]

Older people are at increased risk of mortality with COVID-19.[2][157]

The UK-based National Institute for Health and Care Excellence recommends that all adults admitted to hospital, irrespective of COVID-19 status, have an assessment for frailty, using the clinical frailty scale.[483] Clinical frailty scale external link opens in a new window

One large observational cohort study found that the level of frailty may be a better predictor of mortality risk in hospital patients than even age and presence of comorbidities.[505]

For more detail, see the Prognosis section.

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

Collaborative care is recommended for older people with COVID-19 to help ensure all aspects of care (including comorbidities) are adequately addressed.[2]

Advise patients 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 external link opens in a new window

CDC: interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease 2019 (COVID-19) external link opens in a new window

Discontinue transmission-based precautions (including isolation) and release patients from the care pathway: 10 days after positive test (asymptomatic patients); 10 days after symptom onset plus at least 3 days without fever and respiratory symptoms (symptomatic patients).[2]The US Centers for Disease Control and Prevention (CDC) recommends discontinuing home isolation once at least 10 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing home isolation once at least 10 days have passed since the date of a positive test. Alternatively, it recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used.[494]If the patient is hospitalised, CDC guidance for discontinuing isolation is the same as for moderate disease (see below). Guidance on when to stop isolation depends on local recommendations and may differ between countries. For example, in the UK the isolation period is 10 days in patients with milder disease who are managed in the community.[495]

Plus – monitoring

Treatment recommended for ALL patients in selected patient group

Closely monitor patients with risk factors for severe illness and counsel patients about signs and symptoms of deterioration or complications that require prompt urgent care (e.g., difficulty breathing, chest pain).[2][3]

Check baseline kidney function and monitor closely

Monitor kidney function especially closely if your patient with chronic kidney disease (CKD) or risk factors for CKD becomes ill with an acute condition.[574]

CKD is a significant risk factor for acute kidney injury (AKI).[575]
AKI in patients with COVID-19 may be common, although exact prevalence is uncertain. AKI is associated with increased mortality.[576]
Patients with CKD and 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.
Explain to your patient with CKD that they are at increased risk of developing AKI when they become ill. Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[2]

For any patient with COVID-19 admitted to hospital, including those with CKD, check kidney function on admission, and ensure regular monitoring.

For patients with CKD:
- Compare kidney function with last available results
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion).
Monitor for and respond to oliguria.[574][576]

Plus – symptom management and supportive care

Treatment recommended for ALL patients in selected patient group

Advise patients to avoid lying on their back as this makes coughing ineffective. Use simple measures (e.g., a teaspoon of honey in patients aged 1 year and older) to help cough.[484]A meta-analysis found that honey is superior to usual care (e.g., antitussives) for the improvement of upper respiratory tract infection symptoms, particularly cough frequency and severity.[502]

Advise patients about adequate nutrition and appropriate rehydration. Too much fluid can worsen oxygenation.[2]

Advise patients to improve air circulation by opening a window or door (fans can spread infection and should not be used).[484]

Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate.[2]

Consider treatment for olfactory dysfunction (e.g., olfactory training) if it persists beyond 2 weeks. There is no evidence to support the use of these treatments in patients with COVID-19.[503]

Support patients 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.

The US Center for the Study of Traumatic Stress recommends psychiatrists discuss strategies with their patients to reduce distress and the impact of quarantine, and that they identify and provide additional support to high-risk patients.[577]
Advise your patient on where to find locally relevant information and sources of support, for example:
- Royal College of Psychiatrists: Covid-19 – support for patients and carers external link opens in a new window
There is limited evidence on the effect of quarantine due to the COVID-19 pandemic on people with pre-existing mental health conditions, but it is likely that people who have poor mental health may need additional support.[316]
Consider use of telemedicine to facilitate remote consultations.[578][579]

Plus – set an escalation plan

Treatment recommended for ALL patients in selected patient group

In consultation with the patient with dementia and their carers, agree an escalation plan as early as possible, as you would with any patient (based on expert opinion).

This should include:[580]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of care (e.g., suitability for intubation or intensive care admission).
Escalation plans should take account of advanced care planning, including legally binding advanced directives.[580]

In some situations, the patient with dementia will lack the mental capacity to make decisions for the escalation plan.

Assess and document mental capacity (the ability to make decisions at a specific time a decision needs to be made).[581]Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[582] Assessments should follow the principles in the Act.[582]
If a patient is assessed to lack mental capacity, ensure decisions are made in the best interests of the patient.[581][582]

If the patient is assessed to lack mental capacity, consult with next of kin to make ‘best interests’ decisions.[582]

According to the 2005 Mental Capacity Act in England and Wales, if a patient is unbefriended and a decision is not time-critical, an independent mental capacity advocate (IMCA) should be sought to perform this role.[583]
Check the appropriate legislation for your territory.

Consider – antipyretic/analgesic

Treatment recommended for SOME patients in selected patient group

Paracetamol or ibuprofen are recommended.[2][484]There is no evidence at present of severe adverse events in COVID-19 patients taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or of effects as a result of the use of NSAIDs on acute healthcare utilisation, long-term survival, or quality of life in patients with COVID-19.[496][497][498][499][500][501]

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 patients with chronic kidney disease, heart failure, or asthma

Non-steroidal anti-inflammatory drugs (NSAIDs):

Avoid NSAIDs in patients with chronic kidney disease and/or with heart failure (based on expert opinion)
NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[584]

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 open_in_new: 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 open_in_new: 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

Plus – continue the patient's inhalers as prescribed for asthma or COPD

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.[585][586][587][588][589]

It is still unclear whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an exacerbation of asthma or COPD, but if it were to occur it could further compromise pulmonary reserve.[589]
The overall aim for continuing inhaled corticosteroids is to reduce the risk of an exacerbation of asthma or COPD.[589]
There is no evidence that inhaled corticosteroids are related to COVID-19 infection in people with asthma.[590] There is also no evidence they increase the risks associated with COVID-19 in people with COPD.[588]

Patients being cared for at home or in hospital 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 receptor 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.[585][588][591]
The UK National Institute for Health and Care Excellence rapid guideline on severe asthma recommends that patients who take regular biological therapy for asthma should continue to take this during the COVID-19 pandemic, but if they become ill with COVID-19, patients should contact the specialist team responsible for their care.[591]

Plus – 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 if they think they are having an exacerbation of asthma and to seek medical advice.

Based on the evidence available to date, it is the opinion of the UK Primary Care Respiratory Society (PCRS) that the risk of inadequately treating an asthma exacerbation is likely to be worse than the risk from COVID-19 in most people with asthma.[592]
- The PCRS recommends to follow established guidelines if asthma worsens, and to start oral corticosteroids as indicated for asthma exacerbations.[589][592][593]
Ensure safety netting measures are in place in case the patient does not improve or the situation changes.[592]

Asthma exacerbation and COVID-19 may be difficult to differentiate clinically, and they may present together. Cough and shortness of breath are features of both; however, additional symptoms such as fever, fatigue, and change in taste or smell are more likely to suggest COVID-19.[586] Advise your patient with known COVID-19 to seek medical advice if there is a deterioration in symptoms.

Plus – ensure plans are in place in case of any COPD exacerbation

Plus – weigh up risks versus benefits of prescribed cardiovascular or kidney 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.[2]

Despite concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, due to upregulation of angiotensin-converting enzyme-2 (ACE2) receptor expression, the UK National Institute for Health and Care Excellence states that the current evidence is insufficient to draw any conclusion.[274]
Several professional societies have recommended that during the pandemic patients who are already on these medications (e.g., for hypertension, heart failure, coronary artery disease, CKD, or complications of diabetes) continue to take them (if they don’t have COVID-19). If patients become ill with COVID-19, it is recommended they receive a full clinical assessment by their doctor before making any decisions to stop these medications.[275][276][277][595]

The UK Renal Association and the British Cardiovascular Society recommend following standard current guidance for patients with any intercurrent acute illness when weighing up benefit versus risk of these medications in patients ill with suspected COVID-19.[277][595][596] These include to:

Do an individual clinical assessment
Consider the original indication for any renin-angiotensin-aldosterone system (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.

Consider calculating a frailty score as patients with higher frailty scores may be more likely to experience medication-related harm when acutely unwell (based on expert opinion).

Consider the benefit versus risk of stopping other medications associated with an increased risk of acute kidney injury during intercurrent illness, such as other antihypertensives and diuretics.

If your patient with chronic kidney disease has been taking non-steroidal anti-inflammatory drugs, advise them to stop taking these when they are ill.

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 – advise patients on self-management of their diabetes

Treatment recommended for ALL patients in selected patient group

If a patient with diabetes becomes ill at home with mild COVID-19, advise them to follow sick-day rules and seek medical advice.[597]

Despite limited evidence for this situation, diabetes self-management generally still follows the standard sick-day rules.[598]

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.

Advise patients to follow sick-day rules from their individual healthcare provider or relevant national or regional professional diabetes organisation.[599][600][601][602][603][604]

Key general points include to:[600][601]

Contact their family doctor
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 (e.g., blood glucose levels remain higher than usual, they feel unwell and are not improving, they are not sure how to manage their condition themselves).

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

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, even if they have type 2 diabetes.[605]

People with type 1 diabetes

In addition to the general points above, make sure patients with type 1 diabetes are aware of the need to:[601]

Monitor their blood glucose at least every 4 to 6 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).

Consult local protocols for detailed step-by-step guidance on managing insulin dosing and frequency of blood glucose and ketone monitoring.

If your patient with type 1 diabetes usually takes a sodium-glucose cotransporter-2 (SGLT-2) inhibitor (e.g., dapagliflozin, canagliflozin, empagliflozin), most COVID-related consensus statements recommend these should be stopped during acute illness.[606]

Advise your patient to test their blood for ketones even if their blood glucose is not elevated.[605]
Patients on SGLT-2 inhibitors are at risk of euglycaemic ketoacidosis.[607][608] They should test their blood for ketones even after they have stopped their SGLT-2 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 SGLT-2 inhibitor (e.g., dapagliflozin, canagliflozin, empagliflozin) are recommended, in most COVID-19 consensus statements, to stop this medication during acute illness.[606] They are at risk of euglycaemic ketoacidosis with SGLT-2 inhibitors and should check for blood ketones even once the medication is stopped.[607][608][609] This may be something the patient is not familiar with doing, so organise this to be done urgently.[609]
- Patients who usually take metformin are also advised, in most COVID-related consensus statements, to stop this medication during acute illness.[606] In this situation, metformin increases the risk of lactic acidosis.
- Be aware that withholding diabetes medications such as SGLT-2 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 (based on expert opinion). On the other hand, during illness, some patients may develop hyperglycaemia so may need to temporarily increase their dose.[609] Blood glucose monitoring is crucial to guide these decisions.

Sick-day rules from some diabetes organisations also recommend that patients stop glucagon-like peptide-1 (GLP-1) agonists (e.g., dulaglutide, exenatide, liraglutide, lixisenatide).[610] Other guidance recommends that patients who are on GLP-1 agonists should be monitored closely due to serious adverse effects with dehydration.[611]

Check blood ketones as urinary ketone measurement may be unreliable.

Plus – monitor comorbidities during hospital stay

moderate COVID-19

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

Patients with suspected or confirmed moderate disease (i.e., clinical signs of pneumonia but no signs of severe pneumonia) should be isolated to contain virus transmission.[2]

Manage patients in a healthcare facility, in a community facility, or at home. Home isolation, with telemedicine or remote visits as appropriate, can be considered in low-risk patients. Manage patients at high risk of deterioration and pregnant women in a healthcare facility.[2][3]

Comorbidities in pregnancy and in children

The information in the BMJ Best Practice comorbidities tool relates to non-pregnant adults.

It is not intended for pregnant patients or for children. In these circumstances, please seek specialist obstetric/gynaecology or paediatric advice on how any comorbidities the patient has may affect your management of COVID-19.

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

Consider the presence of any comorbidities when deciding the setting for care and levels of monitoring.

The US Centers for Disease Control and Prevention's list of pre-existing conditions that do, or may increase the risk of severe illness with COVID-19 includes:[157]

Chronic kidney disease
COPD
Coronary artery disease
Heart failure
Type 1 and type 2 diabetes
Asthma (moderate to severe)
Stroke
Hypertension
Dementia.

Older people are at increased risk of mortality with COVID-19.[2][157]

One large observational cohort study found that the level of frailty may be a better predictor of mortality risk in hospital patients than even age and presence of comorbidities.[505]

For more detail, see the Prognosis section.

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

Collaborative care is recommended for older people with COVID-19 to help ensure all aspects of care (including comorbidities) are adequately addressed.[2]

Implement local infection prevention and control procedures when managing patients with COVID-19. For patients in home isolation, advise patients 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 external link opens in a new window

CDC: interim guidance for implementing home care of people not requiring hospitalization for coronavirus disease 2019 (COVID-19) external link opens in a new window

Discontinue transmission-based precautions (including isolation) and release patients from the care pathway 10 days after symptom onset plus at least 3 days without fever and respiratory symptoms.[2][504] The US Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 10 days (not severely immunocompromised) or 20 days (severely immunocompromised) have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing isolation once at least 10 days (not severely immunocompromised) or 20 days (severely immunocompromised) have passed since the date of a positive test. Alternatively, it recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred in these patients.[504]If the patient is isolated at home, CDC guidance for discontinuing isolation is the same as for mild disease (see above). Guidance on when to stop isolation depends on local recommendations and may differ between countries. For example, in the UK the isolation period is 14 days from a positive test in hospitalised patients, and 10 days in patients with milder disease who are managed in the community.[495]

Plus – monitoring

Treatment recommended for ALL patients in selected patient group

Closely monitor patients for signs or symptoms of disease progression. If the patient is being managed at home, counsel them about signs and symptoms of deterioration or complications that require prompt urgent care (e.g., difficulty breathing, chest pain). 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.[2]

Check baseline kidney function and monitor closely

Monitor kidney function especially closely if your patient with chronic kidney disease (CKD) or risk factors for CKD becomes ill with an acute condition.[574]

CKD is a significant risk factor for acute kidney injury (AKI).[575]
AKI in patients with COVID-19 may be common, although exact prevalence is uncertain. AKI is associated with increased mortality.[576]
Patients with CKD and 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.
Explain to your patient with CKD that they are at increased risk of developing AKI when they become ill. Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[2]

For any patient with COVID-19 admitted to hospital, including those with CKD, check kidney function on admission, and ensure regular monitoring.

For patients with CKD:
- Compare kidney function with last available results
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion).
Monitor for and respond to oliguria.[574][576]

Plus – symptom management and supportive care

Treatment recommended for ALL patients in selected patient group

Advise patients about adequate nutrition and appropriate rehydration. Too much fluid can worsen oxygenation.[2]

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.[576] Seek senior advice, particularly for complex patients, such as those with heart failure and/or chronic kidney disease (CKD).[576]

There is a risk of pulmonary oedema with fluid resuscitation in patients with heart failure and/or CKD so monitor closely (every hour initially).
Monitoring should include:[576]
- 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.
Central venous pressure or pulmonary artery catheterisation monitoring may be needed in complex patients.[612]
It’s important to know when to de-escalate fluid therapy. Consider early senior input to support this decision.
If the patient has been volume overloaded with fluid (signs include elevated pulse rate, elevated respiratory rate due to pulmonary oedema, and an elevated JVP with peripheral oedema), stop fluid resuscitation, ask for senior help, and consider intravenous diuretics (based on expert opinion).
Unless there are extenuating circumstances, diuretics and intravenous fluids are not generally given together (based on expert opinion).

Specialist input may be required from a cardiologist and/or nephrologist.

Advise patients to improve air circulation by opening a window or door (fans can spread infection and should not be used).[484]

Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate.[2]

Consider treatment for olfactory dysfunction (e.g., olfactory training) if it persists beyond 2 weeks. There is no evidence to support the use of these treatments in patients with COVID-19.[503]

Support patients 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.

The US Center for the Study of Traumatic Stress recommends psychiatrists discuss strategies with their patients to reduce distress and the impact of quarantine, and that they identify and provide additional support to high-risk patients.[577]
Advise your patient on where to find locally relevant information and sources of support, for example:
- Royal College of Psychiatrists: Covid-19 – support for patients and carers external link opens in a new window
There is limited evidence on the effect of quarantine due to the COVID-19 pandemic on people with pre-existing mental health conditions, but it is likely that people who have poor mental health may need additional support.[316]
Consider use of telemedicine to facilitate remote consultations.[578][579]

Plus – set an escalation plan

Treatment recommended for ALL patients in selected patient group

In consultation with the patient with dementia and their carers, agree an escalation plan as early as possible, as you would with any patient (based on expert opinion).

This should include:[580]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of care (e.g., suitability for intubation or intensive care admission).
Escalation plans should take account of advanced care planning, including legally binding advanced directives.[580]

In some situations, the patient with dementia will lack the mental capacity to make decisions for the escalation plan.

Assess and document mental capacity (the ability to make decisions at a specific time a decision needs to be made).[581]Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[582] Assessments should follow the principles in the Act.[582]
If a patient is assessed to lack mental capacity, ensure decisions are made in the best interests of the patient.[581][582]

If the patient is assessed to lack mental capacity, consult with next of kin to make ‘best interests’ decisions.[582]

According to the 2005 Mental Capacity Act in England and Wales, if a patient is unbefriended and a decision is not time-critical, an independent mental capacity advocate (IMCA) should be sought to perform this role.[583]
Check the appropriate legislation for your territory.

Plus – monitor and manage diabetes

Consider – antibiotics

Consider – antipyretic/analgesic

Treatment recommended for SOME patients in selected patient group

NSAIDs in patients with chronic kidney disease, heart failure, or asthma

Non-steroidal anti-inflammatory drugs (NSAIDs):

Avoid NSAIDs in patients with chronic kidney disease and/or with heart failure (based on expert opinion)
NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[584]

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 open_in_new: 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 open_in_new: 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

Plus – continue the patient's inhalers as prescribed for asthma or COPD

Treatment recommended for ALL patients in selected patient group

It is still unclear whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an exacerbation of asthma or COPD, but if it were to occur it could further compromise pulmonary reserve.[589]
The overall aim for continuing inhaled corticosteroids is to reduce the risk of an exacerbation of asthma or COPD.[589]
There is no evidence that inhaled corticosteroids are related to COVID-19 infection in people with asthma.[590] There is also no evidence they increase the risks associated with COVID-19 in people with COPD.[588]

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 receptor 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.[585][588][591]
The UK National Institute for Health and Care Excellence rapid guideline on severe asthma recommends that patients who take regular biological therapy for asthma should continue to take this during the COVID-19 pandemic, but if they become ill with COVID-19, patients should contact the specialist team responsible for their care.[591]

Plus – weigh up risks versus benefits of prescribed cardiovascular or kidney medication

Treatment recommended for ALL patients in selected patient group

Despite concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, due to upregulation of angiotensin-converting enzyme-2 (ACE2) receptor expression, the UK National Institute for Health and Care Excellence states that the current evidence is insufficient to draw any conclusion.[274]
Several professional societies have recommended that during the pandemic patients who are already on these medications (e.g., for hypertension, heart failure, coronary artery disease, CKD, or complications of diabetes) continue to take them (if they don’t have COVID-19). If patients become ill with COVID-19, it is recommended they receive a full clinical assessment by their doctor before making any decisions to stop these medications.[275][276][277][595]

Do an individual clinical assessment
Consider the original indication for any renin-angiotensin-aldosterone system (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.

Consider calculating a frailty score as patients with higher frailty scores may be more likely to experience medication-related harm when acutely unwell (based on expert opinion).

If your patient with chronic kidney disease has been taking non-steroidal anti-inflammatory drugs, advise them to stop taking these when they are ill.

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

– 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.

Generally a patient with an acute condition (e.g., an infection and illness-related hypotension) is at increased risk of stroke (both ischaemic and haemorrhagic).[613][614]This risk is even higher in anyone with a history of stroke.
Compare the baseline assessment results 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.[615]

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.[2]

Reported neurological manifestations associated with COVID-19 have included stroke.[2]

– 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 a history of dementia. Take a collateral history from family, friends, or carers.[616]

Use a validated scoring system that is feasible in the acute setting, such as:[616]
- The abbreviated mental test score/10 (AMTS/10).[617] British Geriatrics Society: Abbreviated Mental Test Score external link opens in a new window
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.

Assess for delirium whenever a patient with dementia presents with acute illness.[618]The World Health Organization recommends that patients with COVID-19 are assessed for delirium using standardised protocols.[2]

People living with dementia are at increased risk of delirium when they are admitted to hospital and throughout their admission.[619][620]
Delirium is not the same as dementia.[621][622]
Use a screening tool to detect probable delirium, such as:
- The 4-AT.[620][623][624]
People with dementia may have communication difficulties, making it more difficult for them to report symptoms related to COVID-19. Their initial presentation may be with signs of delirium.[625]

Consider the following actions as part of multicomponent care intervention to reduce the risk of delirium during a hospital admission in people with dementia with any acute condition:[620][626]

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.[620]

Challenges specifically related to COVID-19 include:[626]

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:[620]

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.[620]

Check for and treat any reversible causes of delirium.[618] These include:

Infection
Pain
Dehydration
Constipation
Immobility
Poor sleep
Sensory impairment (e.g., ear wax or loss of glasses)
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.

Management of a patient with delirium

Manage patients with delirium initially, if possible with non-pharmacological treatment as recommended in management of delirium in a non-COVID-19 context.[2][618]

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.[626]
The UK National Institute for Health and Care Excellence guideline on delirium (non-COVID-19 setting) 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.[618]
- The NICE COVID-19 rapid guideline on symptom management, intended for managing patients in the community, also recommends haloperidol as an option for the pharmacological management of delirium in patients with COVID-19.[484]
The evidence on the efficacy of antipsychotics for delirium is inconclusive, and hospital protocols may vary.[620]Follow your local hospital protocol for choice of medication.
Always start at the lowest dose for antipsychotic drugs and titrate carefully according to symptoms.[618]Only ever use oral or intramuscular medication (never intravenous) for this purpose.[2]

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.[620]Provide locally available information resources.[626]



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 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 meta-analysis found that people with dementia who take atypical antipsychotics have an increased mortality risk compared with people taking placebo.[627]
A large cohort study of older people found that higher doses of antipsychotics are generally associated with greater risk. Of all the antipsychotics studied, haloperidol had the highest risk associated with its use.[628]
Contrary to popular belief, long-term antipsychotic prescriptions can be safely withdrawn in most people with dementia once behaviour has settled.[629]

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.[618][620]

– ensure monitoring is in place to detect any asthma exacerbation during the 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.[593][630]
See our topic Acute exacerbation of asthma in adults.
Temporarily stop any long-acting muscarinic receptor antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a nebulised 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.

There are currently differences of opinion between organisations in different countries on whether use of a nebuliser is an aerosol-generating procedure and therefore the specific personal protective equipment required.[585][591] Follow your local guidance and protocols. Consider whether it may be clinically appropriate to use a metered-dose inhaler delivered via a spacer device as an alternative delivery mechanism.[631]

– ensure monitoring is in place to detect any COPD exacerbation during the 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, follow the patient’s personalised action plan.

Based on the limited evidence available, the Global Initiative for Chronic Obstructive Lung Disease recommends to follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[585][587][589][594]
See our topic Acute exacerbation of 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.

If a nebuliser is used, bronchodilator therapy via a nebuliser should only be used for 24 to 48 hours and then the patient should be switched back onto their usual inhaler(s).

Temporarily stop any long-acting muscarinic receptor antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a nebulised 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.

– 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 (pre-meal and before bedtime if eating) in any acutely unwell patient with diabetes mellitus.[632]

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

There is no consensus on target blood glucose levels for people with diabetes in hospital with an acute medical condition.

The UK Joint British Diabetes Societies for Inpatient Care (JBDS-IP) recommends an ideal range of 6 to 10 mmol/L (108-180 mg/dL), and an acceptable range of 4 to 12 mmol/L (72-216 mg/dL).[633]A more liberal blood glucose target is considered appropriate if your patient is at high risk of falls, is frail, or has dementia.[633]
- The UK-based National Inpatient Diabetes COVID-19 Response Group makes the same recommendation for patients in hospital with COVID-19.[634]
- Consensus guidance from an international group of experts recommends aiming for levels of between 4 and 10 mmol/L (72 and 180 mg/dL) in patients with COVID-19, but to adjust the lower level to 5 mmol/L (90 mg/dL) in patients who are frail.[611]
The American Diabetes Association recommends a target range of 7.8 to 10.0 mmol/L (140-180 mg/dL) for most critically and non-critically ill patients (not specifically with COVID-19).[632]

Data are still limited on blood glucose control and its association with outcomes for patients with COVID-19.[606]

Hyperglycaemia during the ongoing hospital admission

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.[606]
- Exclude DKA or HHS, both of which require specific urgent management.
- Consider other conditions associated with hyperglycaemia, such as sepsis.[605]
Be aware that the following medications may be associated with hyperglycaemia and may need to be reviewed:[635]
- 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., as a component in antiretroviral therapy, lopinavir/ritonavir may be used to treat some patients with COVID-19).
Some experimental drugs used in the management of COVID-19 may be associated with (or cause) hyperglycaemia. Check local drug formularies for further information before prescribing these therapies in patients with diabetes.
If your patient has persistently elevated blood glucose, they may need insulin therapy (intravenous or subcutaneous protocols). Follow your local protocols on management of hyperglycaemia in patients with COVID-19.
- Infusion pump devices may not be available outside of intensive care unit (ICU) settings, depending on the need for these devices elsewhere. In this situation, some protocols recommend alternative subcutaneous regimens when managing hyperglycaemia and mild DKA.[634][636]
- Be aware that patients with type 2 diabetes in ICU may have significant degrees of insulin resistance.[634]

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.

1 in 5 inpatients with diabetes in England and Wales have a hypoglycaemic episode during their hospital stay.[637]

Causes of hypoglycaemia include:[638]

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[634]
Accidental interruptions to patient feeding, which may occur especially when patients with COVID-19 are nursed in the prone position[634]
Reducing doses of corticosteroids, particularly dexamethasone in patients with COVID-19[634]
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.

Some experimental drugs used in the management of COVID-19 may be associated with (or cause) hypoglycaemia (e.g., hydroxychloroquine). Check local drug formularies for further information before prescribing these therapies in patients with diabetes.

Bedtime snacks can reduce the risk of early morning hypoglycaemia.[637]

Treat hypoglycaemia actively if the blood glucose falls below 4 mmol/L (72 mg/dL).[638]Follow hospital protocol. The JBDS-IP guidelines recommend that you:[638]

Retest blood glucose at 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.

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.[606]

– check the 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 unwell.[639] This is still a recommendation for adults with diabetes admitted to hospital with COVID-19.[605]

A foot check is needed to detect new ulceration or infection, which may be unnoticed by the patient. It may even be the cause of their acute illness (e.g., patient presenting with sepsis, or endocarditis where the original focus of infection is the foot lesion).

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.[640]
- 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

Treatment recommended for ALL patients in selected patient group

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.[641]
- 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).
While data continue to emerge on the psychiatric impact of COVID-19, it is interesting to note that other severe coronavirus infections (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) have been found to be associated with low mood both in the acute phase of the illness as well as at follow-up.[642][643]
Consider other factors that may be influencing the patient’s mental state (e.g., the effect of any illicit drug use or alcohol).[644]

– review current treatment for depression

Treatment recommended for ALL patients in selected patient group

The World Health Organization recommends that potential adverse effects and drug-drug interactions are considered when treating patients with COVID-19.[2] With this in mind, if possible ask the patient which medications they are taking for their depression. Alternatively, review their primary care records for relevant information (if available).

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.[645]
- The severity of symptoms of discontinuation may vary, but it may be unpleasant and may complicate the management of the acute medical condition.[646]
When reviewing current medication, look out for:
- Perceived 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 in 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.[645][647]Consider this issue for all medications prescribed in patients with COVID-19 as well as any experimental therapies (see the Emerging section).
- Drug-drug interactions and their associated adverse effects of particular relevance to patients with COVID-19 include sedation, cardiotoxicity (QT prolongation), and respiratory depression.[2]

Be aware that smoking cessation or switching from tobacco smoking to any other 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.[648][649][650][651] Seek advice on whether any adjustment to the dose of psychotropic medication is appropriate.

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.
- Respiratory depression. Be aware that certain antidepressants may precipitate respiratory depression, especially when co-prescribed with other sedative drugs. Particular caution is needed with tricyclic antidepressants and mirtazapine.
- 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 the 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.[652]
  - 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.

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.

If possible, ask the patient about non-pharmacological treatments for their depression and check 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.

– consider referral to 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.[653][654]

Follow your local protocols/referral pathways in your hospital during the COVID-19 pandemic.

COVID-19 is associated with psychiatric and neurological manifestations including depression.[2]



Evidence: Depression and adherence with treatment

Comorbid depression is linked to poor adherence with recommended physical health treatments, from medication to rehabilitation.[655]

This may lead to worse clinical outcomes, including longer hospital stays.[646][656][657]
Most importantly, depression is linked with excess mortality.[658]

– manage nicotine dependence in current smokers

Treatment recommended for ALL patients in selected patient group

Consider prescribing nicotine replacement therapy to current smokers admitted with an acute condition. This is regardless of intention to quit smoking. However, because there is an increased risk for severe COVID-19 associated with tobacco smoking, in addition to the well-recognised harms, the World Health Organization does recommend smoking cessation.[235][342][659]

Nicotine replacement therapy prevents rapid withdrawal during admission, which can be distressing and uncomfortable.
- Preparations include transdermal patches or, for patients with skin allergies, inhalators, lozenges, gum, or sprays. Dose depends on how many cigarettes are smoked/day and the formulation chosen.
- Use with caution in haemodynamically unstable patients hospitalised with acute stroke, myocardial infarction, and/or uncontrolled hypertension and in patients with severe renal impairment.
- Monitor blood glucose closely if starting nicotine replacement therapy in patients with diabetes.
- Consult your local drug formulary and hospital guidance for more comprehensive details.

Be aware that switching from tobacco smoking to any other 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.[648] Seek advice on whether any adjustment to the dose of psychotropic medication is appropriate.

severe COVID-19

1st line – hospital admission

Patients with suspected or confirmed severe disease are at risk of rapid clinical deterioration and should be admitted to an appropriate healthcare facility under the guidance of a specialist team. Severe disease in adults is defined as having clinical signs of pneumonia plus at least one of the following: respiratory rate >30 breaths/minute, severe respiratory distress, or SpO₂ <90% on room air. Severe disease in children is defined as having clinical signs of pneumonia plus at least one of the following: central cyanosis or SpO₂ <90%, severe respiratory distress, general danger sign, inability to breastfeed or drink, lethargy or unconsciousness, or convulsions).[2]

Comorbidities in pregnancy and in children

The information in the BMJ Best Practice comorbidities tool relates to non-pregnant adults.

It is not intended for pregnant patients or for children. In these circumstances, please seek specialist obstetric/gynaecology or paediatric advice on how any comorbidities the patient has may affect your management of COVID-19.

Assess all adults for frailty on admission to hospital, irrespective of age and COVID-19 status, using the Clinical Frailty Scale (CFS). Clinical frailty scale external link opens in a new window Involve critical care teams in discussions about admission to critical care.[483]A large observational study found that disease outcomes were better predicted by frailty than either age or comorbidity; frailty (CFS score 5-8) was associated with earlier death and longer duration of hospital stay, and these outcomes worsened with increasing frailty after adjustment for age and comorbidity.[505]

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

Consider the presence of any comorbidities when deciding the setting for care and levels of monitoring.

The US Centers for Disease Control and Prevention's list of pre-existing conditions that do, or may increase the risk of severe illness with COVID-19 includes:[157]

Chronic kidney disease
COPD
Coronary artery disease
Heart failure
Type 1 and type 2 diabetes
Asthma (moderate to severe)
Stroke
Hypertension
Dementia.

Older people are at increased risk of mortality with COVID-19.[2][157]

One large observational cohort study found that the level of frailty may be a better predictor of mortality risk in hospital patients than even age and presence of comorbidities.[505]

For more detail, see the Prognosis section.

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

Collaborative care is recommended for older people with COVID-19 to help ensure all aspects of care (including comorbidities) are adequately addressed.[2]

Baseline neurological assessment

Generally a patient with an acute condition (e.g., an infection and illness-related hypotension) is at increased risk of stroke (both ischaemic and haemorrhagic).[613][614] This risk is even higher in anyone with a history of stroke.
Compare the baseline assessment results 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.[615]

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.[2]

Reported neurological manifestations associated with COVID-19 have included stroke.[2]

Implement local infection prevention and control procedures when managing patients with COVID-19.

Pregnant women should be managed by a multidisciplinary team, including obstetric, perinatal, neonatal, and intensive care specialists, as well as midwifery and mental health and psychosocial support. A woman-centred, respectful, skilled approach to care is recommended.[2]The multidisciplinary team should be organised as soon as possible after maternal hypoxemia occurs in order to assess fetal maturity, disease progression, and the best options for delivery.[561]

Discontinue transmission-based precautions (including isolation) and release patients from the care pathway 10 days after symptom onset plus at least 3 days without fever and respiratory symptoms.[2]The US Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 20 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing isolation once at least 20 days have passed since the date of a positive test. Alternatively, it recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred in these patients.[504] Guidance on when to stop isolation depends on local recommendations and may differ between countries. For example, in the UK the isolation period is 14 days from a positive test in hospitalised patients.[495]

Plus – set an escalation plan

Treatment recommended for ALL patients in selected patient group

In consultation with the patient with dementia and their carers, agree an escalation plan as early as possible, as you would with any patient (based on expert opinion).

This should include:[580]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of care (e.g., suitability for intubation or intensive care admission).
Escalation plans should take account of advanced care planning, including legally binding advanced directives.[580]

In some situations, the patient with dementia will lack the mental capacity to make decisions for the escalation plan.

Assess and document mental capacity (the ability to make decisions at a specific time a decision needs to be made).[581]Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[582] Assessments should follow the principles in the Act.[582]
If a patient is assessed to lack mental capacity, ensure decisions are made in the best interests of the patient.[581][582]

If the patient is assessed to lack mental capacity, consult with next of kin to make ‘best interests’ decisions.[582]

According to the 2005 Mental Capacity Act in England and Wales, if a patient is unbefriended and a decision is not time-critical, an independent mental capacity advocate (IMCA) should be sought to perform this role.[583]
Check the appropriate legislation for your territory.

Plus – consider oxygen therapy

Treatment recommended for ALL 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 SpO₂ <90%.[2][3]

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.[2]Some guidelines recommend that SpO₂ should be maintained no higher than 96%.[507]

Some centres may recommend different SpO₂ targets in order to support prioritisation of oxygen flow for the most severely ill patients in hospital. NHS England recommends a target of 92% to 95% (or 90% to 94% if clinically appropriate), for example.[508]

Consider positioning techniques (e.g., high supported sitting, prone position), and airway clearance management to assist with secretion clearance in adults.[2]Oxygen delivery can be increased by using a non-rebreathing mask and prone positioning.[509]Consider a trial of awake prone positioning to improve oxygenation in patients with persistent hypoxaemia despite increasing supplemental oxygen requirements in whom endotracheal intubation is not otherwise indicated.[3] Early self-proning of awake, non-intubated patients has been shown to improve oxygen saturation and may delay or reduce the need for intensive care.[510][511][512][513][514]

Monitor patients closely for signs of progressive acute hypoxaemic respiratory failure.[2][3]

Oxygen therapy in patients with asthma

If the patient’s asthma is stable, follow guideline recommendations for oxygen saturation target for the presenting acute condition (i.e., COVID-19).[660]

Measure resting oxygen saturation in all patients with asthma with any acute illness.[660]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.[593][630]

Follow your local hospital protocol on target oxygen saturations recommended in your hospital during the COVID-19 pandemic for acutely ill patients.
Hypercapnia in asthma is a near fatal sign showing a patient is tiring and needs ventilatory support.[593]Intensive care support is needed immediately.[593]

Oxygen therapy in patients 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)[660]
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.

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. 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.[660]
Re-check ABG after 30 to 60 minutes in all patients.[660]

The British Thoracic Society recommends that standard protocols should be followed in patients admitted to hospital with COVID-19 who also have COPD and evidence of acute on chronic type 2 respiratory failure, as detailed in the sections below.[661]

If a patient with comorbid COPD is critically ill (e.g., shock, sepsis, major head injury, status epilepticus, anaphylaxis, major trauma) and needs high levels of oxygen:

The British Thoracic Society (BTS) recommends an initial target oxygen saturation of 94% to 98%, although more recent evidence suggests an upper target of 96% may be preferred in most cases.[660][662][663] 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.[660]

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):[660]

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.
- The BTS recommends a target oxygen saturation of between 94% and 98% pending ABG results for most acutely ill patients, although more recent evidence suggests an upper target of 96% may be preferred.[660][662][663] This target saturation level may be lower depending on local hospital oxygen supplies (follow your local protocol)
Measure ABG as soon as possible[660]
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.[660]

Plus – symptom management and supportive care

Treatment recommended for ALL patients in selected patient group

Fluids and electrolytes: use cautious fluid management in adults and children without tissue hypoperfusion and fluid responsiveness as aggressive fluid resuscitation may worsen oxygenation.[2]Correct any electrolyte or metabolic abnormalities, such as hyperglycaemia or metabolic acidosis, according to local protocols.[515]

Assess fluid status and manage fluid balance particularly closely

It can be difficult to assess hypotension, low organ perfusion, and shock in a patient with heart failure and/or chronic kidney disease (CKD).

Hypovolaemia may be difficult to assess in a person with heart failure and/or CKD.[664]
Assess:[576]
- Pulse
- Blood pressure
- For postural hypotension
- Peripheral perfusion
- Capillary refill
- Jugular venous pressure
- For presence of pulmonary and peripheral oedema.
Establish the patient’s baseline blood pressure as the fall from baseline is more significant than absolute systolic blood pressure (SBP). 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 (based on expert opinion).
A patient with CKD who is hypotensive, particularly if in shock, needs immediate fluid resuscitation.
- Reassess the patient after initial fluid challenge and get senior input if the patient does not rapidly stabilise. Consider transfer to a more intensive level of care.
A patient with heart failure may need fluid resuscitation but seek senior review to assess volume status and the risk of volume overload. Consider transferring the patient to a more intensive level of care before initiating fluid resuscitation.

Cough: advise patients to avoid lying on their back as this makes coughing ineffective. Use simple measures (e.g., a teaspoon of honey in patients aged 1 year and older) to help cough. Short-term use of a cough suppressant may be considered in select patients (e.g., if the cough is distressing to the patient) provided there are no contraindications.[484]A meta-analysis found that honey is superior to usual care (e.g., antitussives) for the improvement of upper respiratory tract infection symptoms, particularly cough frequency and severity.[502]

Breathlessness: 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). Consider a trial of oxygen, if available. Consider an opioid and benzodiazepine combination in patients with moderate to severe breathlessness or patients who are distressed.[484]

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).[2][484]Consider a benzodiazepine for the management of anxiety or agitation that does not respond to other measures. Consider haloperidol or a phenothiazine for the management of delirium.[484]Low doses of haloperidol (or another suitable antipsychotic) can also be considered for agitation.[2]Non-pharmacological interventions are the mainstay for the management of delirium when possible, and prevention is key.[516]

Baseline cognitive and delirium assessments with collateral history

Do a baseline cognitive assessment at the earliest opportunity in any patient admitted to hospital with an acute condition and with a history of dementia. Take a collateral history from family, friends, or carers.[616]

Use a validated scoring system that is feasible in the acute setting, such as:[616]
- The abbreviated mental test score/10 (AMTS/10).[617] British Geriatrics Society: Abbreviated Mental Test Score external link opens in a new window
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.

People living with dementia are at increased risk of delirium when they are admitted to hospital and throughout their admission.[619][620]
Delirium is not the same as dementia.[621] It is a potentially life-threatening acute, fluctuating change in mental functioning, with inattention, disorganised thinking, and altered levels of consciousness.[622]
Use a screening tool to detect probable delirium, such as:
- The 4-AT.[620][623][624]
People with dementia may have communication difficulties, making it more difficult for them to report symptoms related to COVID-19. Their initial presentation may be with signs of delirium.[625]

Consider the following actions as part of multicomponent care intervention to reduce the risk of delirium during a hospital admission in people with dementia with any acute condition:[620][626]

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.[620]

Challenges specifically related to COVID-19 include:[626]

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:[620]

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.[620]

Check for and treat any reversible causes of delirium.[618] These include:

Infection
Pain
Dehydration
Constipation
Immobility
Poor sleep
Sensory impairment (e.g., ear wax or loss of glasses)
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.

Management of a patient with delirium

Manage patients with delirium initially, if possible with non-pharmacological treatment as recommended in management of delirium in a non-COVID-19 context.[2][618]

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.[626]
The UK National Institute for Health and Care Excellence guideline on delirium (non-COVID-19 setting) 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.[618]
- The NICE COVID-19 rapid guideline on symptom management, intended for managing patients in the community, also recommends haloperidol as an option for the pharmacological management of delirium in patients with COVID-19.[484]
The evidence on the efficacy of antipsychotics for delirium is inconclusive, and hospital protocols may vary.[620] Follow your local hospital protocol for choice of medication.
Always start at the lowest dose for antipsychotic drugs and titrate carefully according to symptoms.[618] Only ever use oral or intramuscular medication (never intravenous) for this purpose.[2]

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.[620] Provide locally available information resources.[626]



Evidence: Risks and safe withdrawal of antipsychotics in older people

Antipsychotics are associated with increased mortality in people with dementia.

A meta-analysis found that people with dementia who take atypical antipsychotics have an increased mortality risk compared with people taking placebo.[627]
A large cohort study of older people found that higher doses of antipsychotics are generally associated with greater risk. Of all the antipsychotics studied, haloperidol had the highest risk associated with its use.[628]
Contrary to popular belief, long-term antipsychotic prescriptions can be safely withdrawn in most people with dementia once behaviour has settled.[629]

Document the diagnosis of delirium clearly.[618][620]

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.[517]

Mental health symptoms: provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia or depression as appropriate.[2]

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.[641]
- 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).
While data continue to emerge on the psychiatric impact of COVID-19, it is interesting to note that other severe coronavirus infections (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) have been found to be associated with low mood both in the acute phase of the illness as well as at follow-up.[642][643]
Consider other factors that may be influencing the patient’s mental state (e.g., the effect of any illicit drug use or alcohol).[644]

Plus – check blood glucose on admission and review diabetes medication (NEVER stop insulin in a person with type 1 diabetes)

Treatment recommended for ALL patients in selected patient group

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

Never stop basal insulin (long-acting/background insulin [e.g., determir, glargine, or degludec]) in a patient with type 1 diabetes who presents with an acute illness, including COVID-19.[611][665]

Insulin deficiency (e.g., due to delayed or missed doses) will rapidly cause ketoacidosis.[665]

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 senior and/or diabetes specialist team (based on expert opinion).

Be aware that COVID-19 appears to increase the risk of potentially life-threatening emergencies including:[605][611]

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:[605]

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).

Diagnose DKA in your patient with known diabetes if:[605]

Blood ketone level is ≥3 mmol/L (≥54 mg/dL) and
Blood pH <7.3 or bicarbonate <15 mmol/L (<270 mg/dL).

Note that the American Diabetes Association and the American Association of Clinical Endocrinologists/American College of Endocrinology each recommend using different criteria for diagnosing DKA compared with the criteria above.[666]

In euglycaemic ketoacidosis, the glucose level may not be significantly elevated.

Diagnose HHS if:[605]

Blood glucose ≥30 mmol/L and
Serum osmolality >320 mOsm/kg and
pH >7.3.

Note that the American Diabetes Association recommends using different criteria for diagnosing HHS compared with the criteria above.[666]

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:[605]

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (e.g., dapagliflozin, canagliflozin, empagliflozin)
- SGLT-2 inhibitors reduce blood glucose reabsorption in the kidneys (independently of insulin metabolism of glucose).[607]
- They can mask underlying ketoacidosis as the patient may have a normal (or near normal) serum glucose level (euglycaemic ketoacidosis).
Metformin
- Metformin is contraindicated in patients with significant renal impairment (estimated GFR <30 mL/minute/1.73 m²), or metabolic acidosis (including lactic acidosis and DKA).
- It is also contraindicated if the patient is at risk of lactic acidosis: for example, with acute kidney injury or tissue hypoxia, including 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.

The patient may need medication adjustment or to start insulin as a temporary measure if their usual SGLT-2 inhibitor or metformin is stopped. Seek diabetes specialist team advice.

Plus – venous thromboembolism prophylaxis

Treatment recommended for ALL patients in selected patient group

Start venous thromboembolism (VTE) prophylaxis in acutely ill hospitalised adults and adolescents with COVID-19 as per the standard of care for other hospitalised patients without COVID-19, provided there are no contraindications. A COVID-19 diagnosis should not influence a paediatrician’s recommendations about VTE prophylaxis in hospitalised children. Pregnant women should be managed by a specialist.[2][3][518][519]

Low molecular weight heparin or fondaparinux are preferred over unfractionated heparin in order to reduce patient contact. Unfractionated heparin is contraindicated in patients with severe thrombocytopenia. Fondaparinux is recommended in patients with a history of heparin-induced thrombocytopenia. Direct oral anticoagulants are not recommended. Mechanical thromboprophylaxis (e.g., intermittent pneumatic compression devices) is recommended if anticoagulation is contraindicated or not available.[2][519][520]

The optimal dose is unknown. Standard prophylaxis doses are recommended over intermediate- or full treatment-dose regimens.[519] Some clinicians are using intermediate- or full treatment-dose regimens rather than prophylactic doses as they are worried about undetected thrombi; however, this may lead to major bleeding events.[521]There are insufficient data to recommend increased anticoagulant doses for VTE prophylaxis in COVID-19 patients outside the setting of a clinical trial.[3]However, some guidelines recommend that escalated doses can be considered in critically ill patients.[518]

Monitor patients for signs and symptoms suggestive of thromboembolism and proceed with appropriate diagnostic and management pathways if clinically suspected.[2]

Routine post-discharge VTE prophylaxis is not generally recommended, except in certain high-risk patients.[3][518][519]

A retrospective analysis of over 4000 patients found that anticoagulation was associated with lower mortality and intubation among hospitalised COVID-19 patients. Therapeutic anticoagulation was associated with lower mortality compared with prophylactic anticoagulation, but the difference was not statistically significant.[522] However, there is little high-quality evidence for VTE prophylaxis in COVID-19 patients; therefore, clinicians should rely on pre-COVID-19 evidence-based principles of anticoagulation management combined with rational approaches to address clinical challenges.[518]

Anticoagulation in patients with chronic kidney disease

Check your local drug formulary/renal handbook for details on prescribing anticoagulants for venous thromboembolism (VTE) prophylaxis in patients with reduced kidney function (chronic kidney disease, acute kidney injury).[667]Patients with impairment of kidney function may have an increased risk of bleeding with certain anticoagulants.

Take care if prescribing low molecular weight heparins (e.g., enoxaparin, dalteparin). Patients with reduced kidney function may need careful monitoring and dose adjustment.
- Check your local drug formulary/renal handbook for guidance on whether to monitor anti-factor Xa. This may depend on the degree of kidney impairment.
- Avoid enoxaparin if the creatinine clearance is <15 mL/minute and reduce the dose if creatinine clearance is 15 to 30 mL/minute.
- A dose reduction of dalteparin is required if the creatinine clearance is <30 mL/minute. Follow your local drug formulary/renal handbook for details of dose reductions for dalteparin.
- Unfractionated heparin may be preferable to low molecular weight heparins, depending on other individual clinical considerations.
Take care if prescribing unfractionated heparin in patients with severely reduced kidney function as dose adjustments may be needed.
Reduce the dose of fondaparinux for the prevention of VTE if the patient has an estimated GFR of 20 to 50 mL/minute/1.73 m².

Seek a nephrologist’s advice if the patient is on renal replacement therapy.

Primary options

enoxaparin: consult specialist for guidance on dose

enoxaparin open_in_new: consult specialist for guidance on dose

enoxaparin: consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

dalteparin open_in_new: consult specialist for guidance on dose

dalteparin: consult specialist for guidance on dose

fondaparinux: consult specialist for guidance on dose

fondaparinux open_in_new: consult specialist for guidance on dose

fondaparinux: consult specialist for guidance on dose

Secondary options

heparin: consult specialist for guidance on dose

heparin open_in_new: consult specialist for guidance on dose

heparin: consult specialist for guidance on dose

Plus – monitoring

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.[2]

Check baseline kidney function and monitor closely

Monitor kidney function especially closely if your patient with chronic kidney disease (CKD) or risk factors for CKD becomes ill with an acute condition.[574]

CKD is a significant risk factor for acute kidney injury (AKI).[575]
AKI in patients with COVID-19 may be common, although exact prevalence is uncertain. AKI is associated with increased mortality.[576]
Patients with CKD and 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.
Explain to your patient with CKD that they are at increased risk of developing AKI when they become ill. Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[2]

For any patient with COVID-19 admitted to hospital, including those with CKD, check kidney function on admission, and ensure regular monitoring.

For patients with CKD:
- Compare kidney function with last available results
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion).
Monitor for and respond to oliguria.[574][576]

Continue to monitor fluid balance particularly closely

There is a risk of pulmonary oedema with fluid resuscitation in patients with heart failure and/or CKD so monitor closely (every hour initially).
Monitoring should include:[576]
- 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.
Central venous pressure or pulmonary artery catheterisation monitoring may be needed in complex patients.[612]
It’s important to know when to de-escalate fluid therapy. Consider early senior input to support this decision.
If the patient has been volume overloaded with fluid (signs include elevated pulse rate, elevated respiratory rate due to pulmonary oedema, and an elevated JVP with peripheral oedema), stop fluid resuscitation, ask for senior help, and consider intravenous diuretics (based on expert opinion).
Unless there are extenuating circumstances, diuretics and intravenous fluids are not generally given together (based on expert opinion).

Specialist input may be required from a cardiologist and/or nephrologist.

Consider – antibiotics

Treatment recommended for SOME patients in selected patient group

Consider empirical antibiotics if there is clinical suspicion of 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 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.[2][3][460]

Some guidelines recommend empirical antibiotics for bacterial pathogens in all patients with community-acquired pneumonia without confirmed COVID-19. It is likely that the bacterial pathogens in patients with COVID-19 and pneumonia are the same as in previous patients with community-acquired pneumonia, and therefore empirical antimicrobial recommendations should be the same.[461]However, the National Institute for Health and Care Excellence in the UK recommends that it is reasonable not to start empirical antimicrobials if you are confident that the clinical features are typical for COVID-19.[460]There is insufficient evidence to recommend empirical broad-spectrum antimicrobials in the absence of another indication.[3]

Some patients may require continued antibiotic therapy once COVID-19 has been confirmed depending on the clinical circumstances (e.g., clinical or microbiological evidence of bacterial infection regardless of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] test results, SARS-CoV-2 test result is positive but clinical features are not typical for COVID-19). In these circumstances, review antibiotic choice based on microbiology results and switch to a narrower-spectrum antibiotic if appropriate, review intravenous antibiotic use within 48 hours and consider switching to oral therapy, and give for a total of 5 days unless there is a clear indication to continue.[460]

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.[2]

Consider – corticosteroid

Treatment recommended for SOME patients in selected patient group

The World Health Organization (WHO) strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with severe COVID-19. This recommendation is based on two meta-analyses that pooled data from eight randomised trials (over 7000 patients), including the UK RECOVERY trial. Moderate-quality evidence suggests that systemic corticosteroids probably reduce 28-day mortality in patients with severe and critical COVID-19. 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.[485][486][523][524]

BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 external link opens in a new window

In the UK, the National Institute for Health and Care Excellence recommends dexamethasone or hydrocortisone in patients with severe COVID-19 (in line with WHO guidance). The marketing authorisations cover this indication in the UK.[483]

NICE: COVID-19 prescribing brief – corticosteroids external link opens in a new window

In Europe, the European Medicines Agency has endorsed the use of dexamethasone for patients with severe disease who require oxygen therapy or mechanical ventilation.[525]

In the US, the National Institutes of Health guideline panel recommends using dexamethasone in adults with COVID-19 who are mechanically ventilated, and in patients who require supplemental oxygen but who are not mechanically ventilated. The panel recommends against using dexamethasone in patients who do not require supplemental oxygen. Alternative corticosteroids may be used in situations where dexamethasone is not available. Assess whether the patient is suitable for corticosteroid therapy before starting therapy.[3] The Infectious Diseases Society of America supports the use of dexamethasone in hospitalised patients with severe disease.[487]

Monitor patients for adverse effects (e.g., hyperglycaemia, secondary infections, psychiatric effects, reactivation of latent infections) and assess for drug-drug interactions.[3]Follow local policies on gastroprotection during corticosteroid treatment. Clinically significant interactions between remdesivir and corticosteroids are unlikely; however, lopinavir/ritonavir may increase hydrocortisone concentrations.[483]

Treatment should stop if the person is discharged from hospital before the 10-day course is completed.[483]

Manage the 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.[668]

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.[669]
COVID-19 is also associated with increased insulin resistance as well as reduced insulin secretion from the pancreatic beta cells.[668]
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.[668]
- The recommended protocol by the UK-based National Inpatient Diabetes COVID-19 Response Group uses subcutaneous insulin.
- The group highlights that sulfonylureas are not recommended in this scenario due to potential impairment of beta cell function and likely severe insulin resistance.[668]

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.

Past incidence of psychiatric complications during corticosteroid therapy increases the risk of recurrence in subsequent treatments.[670]

Monitor for psychiatric adverse effects.[671]

These may vary in severity and include:
- Minor changes in temperament
- Severe mood changes, including manic states
- Cognitive impairment.
Starting corticosteroid treatment is most often linked with manic episodes and delirious states. Chronic corticosteroid therapy most frequently presents with depression.[672]
Effects seem to be dose-related and are more common with long-term regimens or long-acting formulations, and in older patients.[670]This also stands true for patients who have neuropsychiatric adverse effects related to discontinuing long-term corticosteroid therapy.[673]

Liaise with the psychiatry team for advice on appropriate management of the patient’s mood-related complications (based on expert opinion).

This may involve:
- Adjusting the dose or discontinuing the corticosteroid therapy if clinically indicated.
- If discontinuing corticosteroids, being mindful of a possible withdrawal reaction.[673]This can present with weakness, fatigue, gastrointestinal symptoms, and delirium, as well as with psychiatric complications including depression
- Considering prophylactic medication to reduce the risk of psychiatric adverse effects when a patient with a history of mood disorder is started on corticosteroid therapy. Seek expert psychiatric advice.

Primary options

dexamethasone: adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone open_in_new: adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone: adults: 6 mg orally/intravenously once daily for 7-10 days

hydrocortisone: adults: 50 mg orally/intravenously every 8 hours for 7-10 days

hydrocortisone open_in_new: adults: 50 mg orally/intravenously every 8 hours for 7-10 days

hydrocortisone: adults: 50 mg orally/intravenously every 8 hours for 7-10 days

Secondary options

prednisolone: adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone open_in_new: adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone: adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

methylprednisolone: adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days

methylprednisolone open_in_new: adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days

methylprednisolone: adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days

Consider – remdesivir

Treatment recommended for SOME patients in selected patient group

Consider remdesivir in select patients with pneumonia who require supplemental oxygen.[3][487]Remdesivir is conditionally approved in the UK and Europe for this indication in adolescents ≥12 years of age and adults.[526]The emergency-use authorisation in the US covers the treatment of suspected or confirmed COVID-19 in hospitalised children and adults, regardless of disease severity.[527]

Remdesivir may reduce mortality and time to symptom resolution compared with standard of care in patients with severe disease; however, there is no convincing evidence that remdesivir reduces the need for mechanical ventilation.[486]

BMJ interactive tool: drug treatments for covid-19 – living systematic review and network meta-analysis external link opens in a new window

An expert guideline panel makes a weak recommendation for the use of remdesivir in severe disease, and supports more randomised trials as the quality of the evidence is low.[528]

BMJ rapid recommendations: remdesivir for severe covid-19 – a clinical practice guideline external link opens in a new window

A UK National Institute for Health and Care Excellence review suggests there is some benefit with remdesivir compared with placebo for reducing supportive measures including mechanical ventilation and reducing time to recovery in patients who are on oxygen therapy. However, no statistically significant differences were found for mortality and serious adverse events.[529]

Remdesivir can cause gastrointestinal symptoms, elevated transaminase levels, and an increase in prothrombin time. Hypersensitivity reactions have also been reported during and following administration. Remdesivir should not be used in patients with an estimated glomerular filtration rate <30 mL/minute, and it should be used with caution in patients with hepatic impairment. Safety and efficacy has not been evaluated in pregnant women, breastfeeding women, or children. Remdesivir should not be withheld from pregnant women if otherwise indicated. Remdesivir may interact with hydroxychloroquine/chloroquine, but is thought to be safe with corticosteroids.[3]

Take the patient’s comorbidities into account when considering novel therapies

Consider potential adverse effects and drug-drug interactions in all patients being treated for COVID-19.[2]

The World Health Organization has highlighted the following important adverse effects of remdesivir in its interim guidance on the clinical management of COVID-19:[2]
- Renal impairment (remdesivir should not be used in patients with an estimated GFR <30 mL/minute)
- Elevation of hepatic enzymes
- Hypotension
- Gastrointestinal complications
- Rash.
This list of adverse effects is not exhaustive – consult local formulary for further information. Consult your colleagues from relevant specialties and/or a pharmacist for advice.

Primary options

remdesivir: children: consult specialist for guidance on dose; adults: 200 mg intravenously on day 1, followed by 100 mg once daily for 4-9 days

remdesivir open_in_new: children: consult specialist for guidance on dose; adults: 200 mg intravenously on day 1, followed by 100 mg once daily for 4-9 days

remdesivir: children: consult specialist for guidance on dose; adults: 200 mg intravenously on day 1, followed by 100 mg once daily for 4-9 days

Consider – treatment of co-infections

Consider – antipyretic/analgesic

Treatment recommended for SOME patients in selected patient group

Paracetamol or ibuprofen are recommended.[2][507]There is no evidence at present of severe adverse events in COVID-19 patients taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or of effects as a result of the use of NSAIDs on acute healthcare utilisation, long-term survival, or quality of life in patients with COVID-19.[496][497][498][499][500][501]

NSAIDs in patients with chronic kidney disease, heart failure, or asthma

Non-steroidal anti-inflammatory drugs (NSAIDs):

Avoid NSAIDs in patients with chronic kidney disease and/or with heart failure (based on expert opinion)
NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[584]

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 open_in_new: 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 open_in_new: 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

Plus – continue the patient's inhalers as prescribed for asthma or COPD

Treatment recommended for ALL patients in selected patient group

It is still unclear whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an exacerbation of asthma or COPD, but if it were to occur it could further compromise pulmonary reserve.[589]
The overall aim for continuing inhaled corticosteroids is to reduce the risk of an exacerbation of asthma or COPD.[589]
There is no evidence that inhaled corticosteroids are related to COVID-19 infection in people with asthma.[590] There is also no evidence they increase the risks associated with COVID-19 in people with COPD.[588]

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 receptor 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.[585][588][591]
The UK National Institute for Health and Care Excellence rapid guideline on severe asthma recommends that patients who take regular biological therapy for asthma should continue to take this during the COVID-19 pandemic, but if they become ill with COVID-19, patients should contact the specialist team responsible for their care.[591]

Plus – weigh up risks versus benefits of prescribed cardiovascular or kidney medication

Treatment recommended for ALL patients in selected patient group

Despite concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, due to upregulation of angiotensin-converting enzyme-2 (ACE2) receptor expression, the UK National Institute for Health and Care Excellence states that the current evidence is insufficient to draw any conclusion.[274]
Several professional societies have recommended that during the pandemic patients who are already on these medications (e.g., for hypertension, heart failure, coronary artery disease, CKD, or complications of diabetes) continue to take them (if they don’t have COVID-19). If patients become ill with COVID-19, it is recommended they receive a full clinical assessment by their doctor before making any decisions to stop these medications.[275][276][277][595]

Do an individual clinical assessment
Consider the original indication for any renin-angiotensin-aldosterone system (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.

Consider calculating a frailty score as patients with higher frailty scores may be more likely to experience medication-related harm when acutely unwell (based on expert opinion).

If your patient with chronic kidney disease has been taking non-steroidal anti-inflammatory drugs, advise them to stop taking these when they are ill.

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 – experimental therapies

Treatment recommended for SOME patients in selected patient group

Consider experimental therapies (e.g., convalescent plasma, lopinavir/ritonavir) only in the context of a clinical trial or according to local protocols.[2]See the Emerging external link opens in a new windowsection for more information.

Take the patient’s comorbidities into account when considering experimental therapies

The World Health Organization (WHO) recommends that potential adverse effects and drug-drug interactions are considered in patients being treated for COVID-19.[2]

An important example of this, in a patient on medication for a comorbidity, is the use of a certain drug for COVID-19 that prolongs the QT interval when the patient is already prescribed another drug, for the comorbidity, that also causes QT prolongation. Considerable caution is required.

With this in mind, consider your patient’s medication and comorbidities.

The WHO has highlighted the following in its interim guidance on the clinical management of COVID-19 as important adverse effects of some of the experimental therapies:[2]
- Lopinavir/ritonavir: the most common adverse effects are gastrointestinal
- Umifenovir: diarrhoea, nausea
- Favipiravir: QT interval prolongation
- Interferon beta: pyrexia, rhabdomyolysis
- Tocilizumab: upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased alanine aminotransferase, injection-site reactions
- Hydroxychloroquine/chloroquine ± azithromycin: each can cause QT prolongation and taken together can increase the risk of cardiotoxicity.

Follow local drug protocol guidelines and consult senior colleagues prior to initiating any novel therapies. Certain drugs should only be used in the context of a clinical trial.

Consider adverse effects as well as possible drug-drug interactions in light of your patient’s comorbidities and symptoms.
This list of adverse effects is not exhaustive – consult local formulary for further information. Consult your colleagues from relevant specialties and/or a pharmacist for advice.

Consider – plan for discharge and rehabilitation

Treatment recommended for SOME patients in selected patient group

Routinely assess older patients for mobility, functional swallow, cognitive impairment, and mental health concerns, and based on that assessment determine whether the patient is ready for discharge, and whether the patient has any rehabilitation and follow-up requirements.[2]

Ensure plans are in place for follow-up of comorbidities

Ensure the patient has follow-up plans in place concerning any comorbidities as well as discharge and follow-up criteria related to COVID-19.

Knowledge and experience concerning the rehabilitation needs of patients post-hospital discharge is still increasing.[674][675]
COVID-19 may have long-term effects that relate to other comorbidities. UK-based patients with certain comorbidities may find the following sources of information useful:
- Asthma UK and British Lung Foundation: post-COVID hub external link opens in a new window
- Diabetes UK: your safe discharge from hospital – an information leaflet for people with diabetes external link opens in a new window
Follow your local protocols and ask advice from relevant speciality teams.
Consider use of telemedicine to facilitate remote consultations in selected patients.[578][579]

Consider – palliative care

Plus – monitor comorbidities during hospital stay

– ensure monitoring is in place to detect any asthma exacerbation during the 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.[593][630]
See our topic Acute exacerbation of asthma in adults.
Temporarily stop any long-acting muscarinic receptor antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a nebulised 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 the 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, follow the patient’s personalised action plan.

Based on the limited evidence available, the Global Initiative for Chronic Obstructive Lung Disease recommends to follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[585][587][589][594]
See our topic Acute exacerbation of 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.

If a nebuliser is used, bronchodilator therapy via a nebuliser should only be used for 24 to 48 hours and then the patient should be switched back onto their usual inhaler(s).

Ensure to re-prescribe the LAMA once the nebuliser treatment has been stopped.

– 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 (pre-meal and before bedtime if eating) in any acutely unwell patient with diabetes mellitus.[632]

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

There is no consensus on target blood glucose levels for people with diabetes in hospital with an acute medical condition.

The UK Joint British Diabetes Societies for Inpatient Care (JBDS-IP) recommends an ideal range of 6 to 10 mmol/L (108-180 mg/dL), and an acceptable range of 4 to 12 mmol/L (72-216 mg/dL).[633]A more liberal blood glucose target is considered appropriate if your patient is at high risk of falls, is frail, or has dementia.[633]
- The UK-based National Inpatient Diabetes COVID-19 Response Group makes the same recommendation for patients in hospital with COVID-19.[634]
- Consensus guidance from an international group of experts recommends aiming for levels of between 4 and 10 mmol/L (72 and 180 mg/dL) in patients with COVID-19, but to adjust the lower level to 5 mmol/L (90 mg/dL) in patients who are frail.[611]
The American Diabetes Association recommends a target range of 7.8 to 10.0 mmol/L (140-180 mg/dL) for most critically and non-critically ill patients (not specifically with COVID-19).[632]

Data are still limited on blood glucose control and its association with outcomes for patients with COVID-19.[606]

Hyperglycaemia during the ongoing hospital admission

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.[606]
- Exclude DKA or HHS, both of which require specific urgent management.
- Consider other conditions associated with hyperglycaemia, such as sepsis.[605]
Be aware that the following medications may be associated with hyperglycaemia and may need to be reviewed:[635]
- 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., as a component in antiretroviral therapy, lopinavir/ritonavir may be used to treat some patients with COVID-19).
Some experimental drugs used in the management of COVID-19 may be associated with (or cause) hyperglycaemia. Check local drug formularies for further information before prescribing these therapies in patients with diabetes.
If your patient has persistently elevated blood glucose, they may need insulin therapy (intravenous or subcutaneous protocols). Follow your local protocols on management of hyperglycaemia in patients with COVID-19.
- Infusion pump devices may not be available outside of intensive care unit (ICU) settings, depending on the need for these devices elsewhere. In this situation, some protocols recommend alternative subcutaneous regimens when managing hyperglycaemia and mild DKA.[634][636]
- Be aware that patients with type 2 diabetes in ICU may have significant degrees of insulin resistance.[634]

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.

1 in 5 inpatients with diabetes in England and Wales have a hypoglycaemic episode during their hospital stay.[637]

Causes of hypoglycaemia include:[638]

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[634]
Accidental interruptions to patient feeding, which may occur especially when patients with COVID-19 are nursed in the prone position[634]
Reducing doses of corticosteroids, particularly dexamethasone in patients with COVID-19[634]
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.

Bedtime snacks can reduce the risk of early morning hypoglycaemia.[637]

Treat hypoglycaemia actively if the blood glucose falls below 4 mmol/L (72 mg/dL).[638]Follow hospital protocol. The JBDS-IP guidelines recommend that you:[638]

Retest blood glucose at 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.

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.[606]

– check the patient’s feet

Treatment recommended for ALL patients in selected patient group

A foot check is needed to detect new ulceration or infection, which may be unnoticed by the patient. It may even be the cause of their acute illness (e.g., patient presenting with sepsis, or endocarditis where the original focus of infection is the foot lesion).

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.[640]
- 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.

– review current treatment for depression

Treatment recommended for ALL patients in selected patient group

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.[645]
- The severity of symptoms of discontinuation may vary, but it may be unpleasant and may complicate the management of the acute medical condition.[646]
When reviewing current medication, look out for:
- Perceived 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 in 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.[645][647]Consider this issue for all medications prescribed in patients with COVID-19 as well as any experimental therapies (see the Emerging section).
- Drug-drug interactions and their associated adverse effects of particular relevance to patients with COVID-19 include sedation, cardiotoxicity (QT prolongation), and respiratory depression.[2]

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.
- Respiratory depression. Be aware that certain antidepressants may precipitate respiratory depression, especially when co-prescribed with other sedative drugs. Particular caution is needed with tricyclic antidepressants and mirtazapine.
- 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 the 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.[652]
  - 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.

If possible, ask the patient about non-pharmacological treatments for their depression and check 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.

– consider referral to 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.[653][654]

Follow your local protocols/referral pathways in your hospital during the COVID-19 pandemic.

COVID-19 is associated with psychiatric and neurological manifestations including depression.[2]



Evidence: Depression and adherence with treatment

Comorbid depression is linked to poor adherence with recommended physical health treatments, from medication to rehabilitation.[655]

This may lead to worse clinical outcomes, including longer hospital stays.[646][656][657]
Most importantly, depression is linked with excess mortality.[658]

– manage nicotine dependence in current smokers

Treatment recommended for ALL patients in selected patient group

Nicotine replacement therapy prevents rapid withdrawal during admission, which can be distressing and uncomfortable.
- Preparations include transdermal patches or, for patients with skin allergies, inhalators, lozenges, gum, or sprays. Dose depends on how many cigarettes are smoked/day and the formulation chosen.
- Use with caution in haemodynamically unstable patients hospitalised with acute stroke, myocardial infarction, and/or uncontrolled hypertension and in patients with severe renal impairment.
- Monitor blood glucose closely if starting nicotine replacement therapy in patients with diabetes.
- Consult your local drug formulary and hospital guidance for more comprehensive details.

critical COVID-19

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

Patients with critical disease (i.e., presence of acute respiratory distress syndrome, sepsis, or septic shock) should be admitted or transferred to an intensive/critical care unit under the guidance of a specialist team.[2]

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:

The patient is shocked or hypotensive[676]
The patient has a blood pressure ≥40 mmHg lower than baseline, has developed orthostatic hypotension (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[677]), or has developed postural symptoms(based on expert opinion)
- Establish the 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, it may be appropriate to withhold medication that may lower blood pressure. 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.

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

Most patients won’t tolerate restarting all medications at the original doses in one go.
Restart one at a time at a lower dose and ask the patient's general practitioner to titrate back to normal dose.
If it is not clinically appropriate to restart these medicines before discharge, make sure the patient/carers understand the need to arrange a clinical review with the patient’s general practitioner to decide when the medications can be re-introduced. Ensure you have communicated clearly to the patient’s general practitioner.

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.[484]

Set an escalation plan

In consultation with the patient with dementia and their carers, agree an escalation plan as early as possible, as you would with any patient (based on expert opinion).

This should include:[580]
- Resuscitation status (i.e., ‘Do Not Attempt Cardiopulmonary Resuscitation’ [DNACPR] decision)
- Ceiling of care (e.g., suitability for intubation or intensive care admission).
Escalation plans should take account of advanced care planning, including legally binding advanced directives.[580]

In some situations, the patient with dementia will lack the mental capacity to make decisions for the escalation plan.

Assess and document mental capacity (the ability to make decisions at a specific time a decision needs to be made).[581]Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[582]Assessments should follow the principles in the Act.[582]
If a patient is assessed to lack mental capacity, ensure decisions are made in the best interests of the patient.[581][582]

If the patient is assessed to lack mental capacity, consult with next of kin to make ‘best interests’ decisions.[582]

According to the 2005 Mental Capacity Act in England and Wales, if a patient is unbefriended and a decision is not time-critical, an independent mental capacity advocate (IMCA) should be sought to perform this role.[583]
Check the appropriate legislation for your territory.

Implement local infection prevention and control procedures when managing patients with COVID-19.

Comorbidities in pregnancy and in children

The information in the BMJ Best Practice comorbidities tool relates to non-pregnant adults.

It is not intended for pregnant patients or for children. In these circumstances, please seek specialist obstetric/gynaecology or paediatric advice on how any comorbidities the patient has may affect your management of COVID-19.

Discontinue transmission-based precautions (including isolation) and release patients from the care pathway 10 days after symptom onset plus at least 3 days without fever and respiratory symptoms.[2] The US Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 20 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing isolation once at least 20 days have passed since the date of a positive test. Alternatively, it recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred in these patients.[504]Guidance on when to stop isolation depends on local recommendations and may differ between countries. For example, in the UK the isolation period is 14 days from a positive test in hospitalised patients.[495]

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.

Venous thromboembolism prophylaxis is recommended in critically ill patients. Low molecular weight heparin is the preferred option, with unfractionated heparin considered a suitable alternative and preferred over fondaparinux.[519] See Severe COVID-19 above for more detailed information.

Implement standard interventions to prevent complications associated with critical illness.[2]

Check baseline kidney function and monitor closely

Monitor kidney function especially closely if your patient with chronic kidney disease (CKD) or risk factors for CKD becomes ill with an acute condition.[574]

CKD is a significant risk factor for acute kidney injury (AKI).[575]
AKI in patients with COVID-19 may be common, although exact prevalence is uncertain. AKI is associated with increased mortality.[576]
Patients with CKD and 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.
Explain to your patient with CKD that they are at increased risk of developing AKI when they become ill. Have mechanisms in place so patients being treated at home can be monitored closely for signs of disease progression.[2]

For any patient with COVID-19 admitted to hospital, including those with CKD, check kidney function on admission, and ensure regular monitoring.

For patients with CKD:
- Compare kidney function with last available results
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion).
Monitor for and respond to oliguria.[574][576]

Assess fluid status and manage fluid balance particularly closely

It can be difficult to assess hypotension, low organ perfusion, and shock in a patient with heart failure and/or chronic kidney disease (CKD).

Hypovolaemia may be difficult to assess in a person with heart failure and/or CKD.[664]
Assess:[576]
- Pulse
- Blood pressure
- For postural hypotension
- Peripheral perfusion
- Capillary refill
- Jugular venous pressure
- For presence of pulmonary and peripheral oedema.
Establish the patient’s baseline blood pressure as the fall from baseline is more significant than absolute systolic blood pressure (SBP). 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 (based on expert opinion).
A patient with CKD who is hypotensive, particularly if in shock, needs immediate fluid resuscitation.
- Reassess the patient after initial fluid challenge and get senior input if the patient does not rapidly stabilise. Consider transfer to a more intensive level of care.
A patient with heart failure may need fluid resuscitation but seek senior review to assess volume status and the risk of volume overload. Consider transferring the patient to a more intensive level of care before initiating fluid resuscitation.

Continue to monitor fluid balance particularly closely

There is a risk of pulmonary oedema with fluid resuscitation in patients with heart failure and/or CKD so monitor closely (every hour initially).
Monitoring should include:[576]
- 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.
Central venous pressure or pulmonary artery catheterisation monitoring may be needed in complex patients.[612]
It’s important to know when to de-escalate fluid therapy. Consider early senior input to support this decision.
If the patient has been volume overloaded with fluid (signs include elevated pulse rate, elevated respiratory rate due to pulmonary oedema, and an elevated JVP with peripheral oedema), stop fluid resuscitation, ask for senior help, and consider intravenous diuretics (based on expert opinion).
Unless there are extenuating circumstances, diuretics and intravenous fluids are not generally given together (based on expert opinion).

Specialist input may be required from a cardiologist and/or nephrologist.

NSAIDs in patients with chronic kidney disease, heart failure, or asthma

Non-steroidal anti-inflammatory drugs (NSAIDs):

Avoid NSAIDs in patients with chronic kidney disease and/or with heart failure (based on expert opinion)
NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[584]

Baseline cognitive and delirium assessments with collateral history

Use a validated scoring system that is feasible in the acute setting, such as:[616]
- The abbreviated mental test score/10 (AMTS/10).[617] British Geriatrics Society: Abbreviated Mental Test Score external link opens in a new window
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.

People living with dementia are at increased risk of delirium when they are admitted to hospital and throughout their admission.[619][620]
Delirium is not the same as dementia.[621] It is a potentially life-threatening acute, fluctuating change in mental functioning, with inattention, disorganised thinking, and altered levels of consciousness.[622]
Use a screening tool to detect probable delirium, such as:
- The 4-AT.[620][623][624]
People with dementia may have communication difficulties, making it more difficult for them to report symptoms related to COVID-19. Their initial presentation may be with signs of delirium.[625]

Consider the following actions as part of multicomponent care intervention to reduce the risk of delirium during a hospital admission in people with dementia with any acute condition:[620][626]

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.[620]

Challenges specifically related to COVID-19 include:[626]

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:[620]

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.[620]

Check for and treat any reversible causes of delirium.[618] These include:

Infection
Pain
Dehydration
Constipation
Immobility
Poor sleep
Sensory impairment (e.g., ear wax or loss of glasses)
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.

Management of a patient with delirium

Manage patients with delirium initially, if possible with non-pharmacological treatment as recommended in management of delirium in a non-COVID-19 context.[2][618]

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.[626]
The UK National Institute for Health and Care Excellence guideline on delirium (non-COVID-19 setting) 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.[618]
- The NICE COVID-19 rapid guideline on symptom management, intended for managing patients in the community, also recommends haloperidol as an option for the pharmacological management of delirium in patients with COVID-19.[484]
The evidence on the efficacy of antipsychotics for delirium is inconclusive, and hospital protocols may vary.[620] Follow your local hospital protocol for choice of medication.
Always start at the lowest dose for antipsychotic drugs and titrate carefully according to symptoms.[618] Only ever use oral or intramuscular medication (never intravenous) for this purpose.[2]

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.[620] Provide locally available information resources.[626]



Evidence: Risks and safe withdrawal of antipsychotics in older people

Antipsychotics are associated with increased mortality in people with dementia.

A meta-analysis found that people with dementia who take atypical antipsychotics have an increased mortality risk compared with people taking placebo.[627]
A large cohort study of older people found that higher doses of antipsychotics are generally associated with greater risk. Of all the antipsychotics studied, haloperidol had the highest risk associated with its use.[628]
Contrary to popular belief, long-term antipsychotic prescriptions can be safely withdrawn in most people with dementia once behaviour has settled.[629]

Document the diagnosis of delirium clearly.[618][620]

Baseline neurological assessment

Generally a patient with an acute condition (e.g., an infection and illness-related hypotension) is at increased risk of stroke (both ischaemic and haemorrhagic).[613][614] This risk is even higher in anyone with a history of stroke.
Compare the baseline assessment results 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.[615]

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.[2]

Reported neurological manifestations associated with COVID-19 have included stroke.[2]

Anticoagulation in patients with chronic kidney disease

Take care if prescribing low molecular weight heparins (e.g., enoxaparin, dalteparin). Patients with reduced kidney function may need careful monitoring and dose adjustment.
- Check your local drug formulary/renal handbook for guidance on whether to monitor anti-factor Xa. This may depend on the degree of kidney impairment.
- Avoid enoxaparin if the creatinine clearance is <15 mL/minute and reduce the dose if creatinine clearance is 15 to 30 mL/minute.
- A dose reduction of dalteparin is required if the creatinine clearance is <30 mL/minute. Follow your local drug formulary/renal handbook for details of dose reductions for dalteparin.
- Unfractionated heparin may be preferable to low molecular weight heparins, depending on other individual clinical considerations.
Take care if prescribing unfractionated heparin in patients with severely reduced kidney function as dose adjustments may be needed.
Reduce the dose of fondaparinux for the prevention of VTE if the patient has an estimated GFR of 20 to 50 mL/minute/1.73 m².

Seek a nephrologist’s advice if the patient is on renal replacement therapy.

Plus – check blood glucose on admission and review diabetes medication (NEVER stop insulin in a person with type 1 diabetes)

Treatment recommended for ALL patients in selected patient group

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

Insulin deficiency (e.g., due to delayed or missed doses) will rapidly cause ketoacidosis.[665]

Be aware that COVID-19 appears to increase the risk of potentially life-threatening emergencies including:[605][611]

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:[605]

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).

Diagnose DKA in your patient with known diabetes if:[605]

Blood ketone level is ≥3 mmol/L (≥54 mg/dL) and
Blood pH <7.3 or bicarbonate <15 mmol/L (<270 mg/dL).

In euglycaemic ketoacidosis, the glucose level may not be significantly elevated.

Diagnose HHS if:[605]

Blood glucose ≥30 mmol/L and
Serum osmolality >320 mOsm/kg and
pH >7.3.

Note that the American Diabetes Association recommends using different criteria for diagnosing HHS compared with the criteria above.[666]

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:[605]

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (e.g., dapagliflozin, canagliflozin, empagliflozin)
- SGLT-2 inhibitors reduce blood glucose reabsorption in the kidneys (independently of insulin metabolism of glucose).[607]
- They can mask underlying ketoacidosis as the patient may have a normal (or near normal) serum glucose level (euglycaemic ketoacidosis).
Metformin
- Metformin is contraindicated in patients with significant renal impairment (estimated GFR <30 mL/minute/1.73 m²), or metabolic acidosis (including lactic acidosis and DKA).
- It is also contraindicated if the patient is at risk of lactic acidosis: for example, with acute kidney injury or tissue hypoxia, including 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.

The patient may need medication adjustment or to start insulin as a temporary measure if their usual SGLT-2 inhibitor or metformin is stopped. Seek diabetes specialist team advice.

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

Treatment recommended for ALL patients in selected patient group

Consider a trial of high-flow nasal oxygen (HFNO) or non-invasive ventilation (e.g., continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) in selected patients with mild acute respiratory distress syndrome.[2]

Airborne precautions are recommended for these interventions (including bubble CPAP) due to uncertainty about the potential for aerosolisation.[2]

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.[2]

There is ongoing debate about the optimal mode of respiratory support before mechanical ventilation.[534]NHS England recommends CPAP as the preferred form of non-invasive ventilation in patients with hypoxaemic (type 1) respiratory failure. It doesn't advocate the use of HFNO based on a lack of efficacy, oxygen use (HFNO can place a strain on oxygen supplies with the risk of site supply failure), and infection spread.[535]Other guidelines recommend HFNO over non-invasive ventilation, unless HFNO is not available.[3][507]Despite the trend to avoid HFNO, it has been shown to have a similar risk of aerosol generation to standard oxygen masks.[536]

Early CPAP may provide a bridge to invasive mechanical ventilation. Reserve the use of BiPAP for patients with hypercapnic acute on chronic ventilatory failure (type 2 respiratory failure).[535]

Monitor patients closely for acute deterioration. If patients do not improve after a short trial of these interventions, they require urgent endotracheal intubation.[2][507]

Oxygen therapy in patients with asthma

If the patient’s asthma is stable, follow guideline recommendations for oxygen saturation target for the presenting acute condition (i.e., COVID-19).[660]

Measure resting oxygen saturation in all patients with asthma with any acute illness.[660]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.[593][630]

Follow your local hospital protocol on target oxygen saturations recommended in your hospital during the COVID-19 pandemic for acutely ill patients.
Hypercapnia in asthma is a near fatal sign showing a patient is tiring and needs ventilatory support.[593]Intensive care support is needed immediately.[593]

Oxygen therapy in patients 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)[660]
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.

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.[660]
Re-check ABG after 30 to 60 minutes in all patients.[660]

If a patient with comorbid COPD is critically ill (e.g., shock, sepsis, major head injury, status epilepticus, anaphylaxis, major trauma) and needs high levels of oxygen:

The British Thoracic Society (BTS) recommends an initial target oxygen saturation of 94% to 98%, although more recent evidence suggests an upper target of 96% may be preferred in most cases.[660][662][663] 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.[660]

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.
- The BTS recommends a target oxygen saturation of between 94% and 98% pending ABG results for most acutely ill patients, although more recent evidence suggests an upper target of 96% may be preferred.[660][662][663] This target saturation level may be lower depending on local hospital oxygen supplies (follow your local protocol)
Measure ABG as soon as possible[660]
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.[660]

Plus – consider invasive mechanical ventilation

Treatment recommended for ALL patients in selected patient group

Consider endotracheal intubation and mechanical ventilation in patients who are acutely deteriorating despite advanced oxygen/non-invasive ventilatory support measures.[2][3]

Endotracheal intubation should be performed by an experienced provider using airborne precautions.[2]Intubation by video laryngoscopy is recommended if possible.[3]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.[2]

Mechanically ventilated patients with acute respiratory distress syndrome (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 preferred 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.[2][3][507]NHS England recommends a low PEEP strategy in patients with normal compliance where recruitment may not be required.[540]

Although some patients with COVID-19 pneumonia meet the criteria for ARDS, there is some discussion about whether COVID-19 pneumonia is its own specific disease with atypical phenotypes. Anecdotal evidence suggests that the main characteristic of the atypical presentation is the dissociation between well-preserved lung mechanics and the severity of hypoxaemia.[541][542][543][544][545][546] However, this approach has been criticised.[547][548]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.[549]As a consequence of this, some clinicians have warned that protocol-driven ventilator use may be causing 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.[541]PEEP should always be carefully titrated.[509]

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.[2][3][507]Longer durations may be feasible in some patients.[550]

Lung recruitment manoeuvres are suggested, but staircase recruitment manoeuvres are not recommended.[3][507]

Consider – inhaled pulmonary vasodilator

Consider – extracorporeal membrane oxygenation

Treatment recommended for SOME patients in selected patient group

Consider extracorporeal membrane oxygenation (ECMO) according to availability and expertise if the above methods fail.[2][507][554][555] ECMO is not suitable for all patients, and only those who meet certain inclusion criteria may be considered for ECMO.[556]

There is insufficient evidence to recommend either for or against the routine use of ECMO.[3] Preliminary data on the use of ECMO in patients with COVID-19 was not promising.[557][558] However, more recent data indicate that the estimated 60-day survival rate of ECMO-rescued patients with COVID-19 (31%) was similar to that of previous studies of ECMO for severe ARDS.[559]

Single-access, dual-stage venovenous ECMO with early extubation appears to be safe and effective in patients with COVID-19 respiratory failure.[560]

Consider – management of sepsis/septic shock

Consider – corticosteroid

Treatment recommended for SOME patients in selected patient group

The World Health Organization (WHO) strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with critical COVID-19. This recommendation is based on two meta-analyses that pooled data from eight randomised trials (over 7000 patients), including the UK RECOVERY trial. Moderate-quality evidence suggests that systemic corticosteroids probably reduce 28-day mortality in patients with severe and critical COVID-19. 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.[485][486][523][524]

BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 external link opens in a new window

In the UK, the National Institute for Health and Care Excellence recommends dexamethasone or hydrocortisone in patients with critical COVID-19 (in line with WHO guidance). The marketing authorisations cover this indication in the UK.[483]

NICE: COVID-19 prescribing brief – corticosteroids external link opens in a new window

In Europe, the European Medicines Agency has endorsed the use of dexamethasone for patients with severe disease who require oxygen therapy or mechanical ventilation.[525]

Treatment should stop if the person is discharged from hospital before the 10-day course is completed.[483]

Manage the 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.[668]

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.[669]
COVID-19 is also associated with increased insulin resistance as well as reduced insulin secretion from the pancreatic beta cells.[668]
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.[668]
- The recommended protocol by the UK-based National Inpatient Diabetes COVID-19 Response Group uses subcutaneous insulin.
- The group highlights that sulfonylureas are not recommended in this scenario due to potential impairment of beta cell function and likely severe insulin resistance.[668]

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.

Past incidence of psychiatric complications during corticosteroid therapy increases the risk of recurrence in subsequent treatments.[670]

Monitor for psychiatric adverse effects.[671]

These may vary in severity and include:
- Minor changes in temperament
- Severe mood changes, including manic states
- Cognitive impairment.
Starting corticosteroid treatment is most often linked with manic episodes and delirious states. Chronic corticosteroid therapy most frequently presents with depression.[672]
Effects seem to be dose-related and are more common with long-term regimens or long-acting formulations, and in older patients.[670]This also stands true for patients who have neuropsychiatric adverse effects related to discontinuing long-term corticosteroid therapy.[673]

Liaise with the psychiatry team for advice on appropriate management of the patient’s mood-related complications (based on expert opinion).

This may involve:
- Adjusting the dose or discontinuing the corticosteroid therapy if clinically indicated.
- If discontinuing corticosteroids, being mindful of a possible withdrawal reaction.[673]This can present with weakness, fatigue, gastrointestinal symptoms, and delirium, as well as with psychiatric complications including depression
- Considering prophylactic medication to reduce the risk of psychiatric adverse effects when a patient with a history of mood disorder is started on corticosteroid therapy. Seek expert psychiatric advice.

Primary options

dexamethasone: adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone open_in_new: adults: 6 mg orally/intravenously once daily for 7-10 days

dexamethasone: adults: 6 mg orally/intravenously once daily for 7-10 days

hydrocortisone: adults: 50 mg orally/intravenously every 8 hours for 7-10 days

hydrocortisone open_in_new: adults: 50 mg orally/intravenously every 8 hours for 7-10 days

hydrocortisone: adults: 50 mg orally/intravenously every 8 hours for 7-10 days

Secondary options

prednisolone: adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone open_in_new: adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

prednisolone: adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days

methylprednisolone: adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days

methylprednisolone open_in_new: adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days

methylprednisolone: adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days

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

Primary options

dexamethasone

dexamethasone open_in_new

dexamethasone

hydrocortisone

hydrocortisone open_in_new

hydrocortisone

Secondary options

prednisolone

prednisolone open_in_new

prednisolone

methylprednisolone

methylprednisolone open_in_new

methylprednisolone

Show drug doses for a patient with no comorbidities

Consider – remdesivir

Treatment recommended for SOME patients in selected patient group

In the US, the National Institutes of Health recommends prioritising remdesivir in hospitalised patients who require supplemental oxygen, but who are not on high-flow oxygen, non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). If a patient progresses to requiring high-flow oxygen, ventilation, or ECMO while on remdesivir, the guidelines panel recommends that the course of remdesivir be completed. The panel does not recommend for or against remdesivir for the treatment of patients who require high-flow oxygen, non-invasive ventilation, mechanical ventilation, or ECMO as there are insufficient data.[3]The Infectious Diseases Society of America recommends remdesivir in hospitalised patients with severe disease who are on oxygen, mechanical ventilation, or ECMO; however, it also recommends prioritising treatment in patients who are on oxygen therapy only when supply is limited.[487]

BMJ interactive tool: drug treatments for covid-19 – living systematic review and network meta-analysis external link opens in a new window

An expert guideline panel makes a weak recommendation for the use of remdesivir in severe disease, and supports more randomised trials as the quality of the evidence is low.[528]

BMJ rapid recommendations: remdesivir for severe covid-19 – a clinical practice guideline external link opens in a new window

Take the patient’s comorbidities into account when considering novel therapies

Consider potential adverse effects and drug-drug interactions in all patients being treated for COVID-19.[2]

The World Health Organization has highlighted the following important adverse effects of remdesivir in its interim guidance on the clinical management of COVID-19:[2]
- Renal impairment (remdesivir should not be used in patients with an estimated GFR <30 mL/minute)
- Elevation of hepatic enzymes
- Hypotension
- Gastrointestinal complications
- Rash.
This list of adverse effects is not exhaustive – consult local formulary for further information. Consult your colleagues from relevant specialties and/or a pharmacist for advice.

Primary options

remdesivir: children: consult specialist for guidance on dose; adults: 200 mg intravenously on day 1, followed by 100 mg once daily for 4-9 days

remdesivir open_in_new: children: consult specialist for guidance on dose; adults: 200 mg intravenously on day 1, followed by 100 mg once daily for 4-9 days

remdesivir: children: consult specialist for guidance on dose; adults: 200 mg intravenously on day 1, followed by 100 mg once daily for 4-9 days

The recommended treatment course is 5 days or until hospital discharge, whichever comes first. Some experts recommend a 10-day course in patients who have not shown clinical improvement after 5 days.[3] A 10-day course is also recommend in patients on mechanical ventilation or ECMO.[487]

Plus – continue the patient's inhalers as prescribed for asthma or COPD

Treatment recommended for ALL patients in selected patient group

It is still unclear whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger an exacerbation of asthma or COPD, but if it were to occur it could further compromise pulmonary reserve.[589]
The overall aim for continuing inhaled corticosteroids is to reduce the risk of an exacerbation of asthma or COPD.[589]
There is no evidence that inhaled corticosteroids are related to COVID-19 infection in people with asthma.[590] There is also no evidence they increase the risks associated with COVID-19 in people with COPD.[588]

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 receptor 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.[585][588][591]
The UK National Institute for Health and Care Excellence rapid guideline on severe asthma recommends that patients who take regular biological therapy for asthma should continue to take this during the COVID-19 pandemic, but if they become ill with COVID-19, patients should contact the specialist team responsible for their care.[591]

Plus – weigh up risks versus benefits of prescribed cardiovascular or kidney medication

Treatment recommended for ALL patients in selected patient group

Despite concern about possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, due to upregulation of angiotensin-converting enzyme-2 (ACE2) receptor expression, the UK National Institute for Health and Care Excellence states that the current evidence is insufficient to draw any conclusion.[274]
Several professional societies have recommended that during the pandemic patients who are already on these medications (e.g., for hypertension, heart failure, coronary artery disease, CKD, or complications of diabetes) continue to take them (if they don’t have COVID-19). If patients become ill with COVID-19, it is recommended they receive a full clinical assessment by their doctor before making any decisions to stop these medications.[275][276][277][595]

Do an individual clinical assessment
Consider the original indication for any renin-angiotensin-aldosterone system (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.

Consider calculating a frailty score as patients with higher frailty scores may be more likely to experience medication-related harm when acutely unwell (based on expert opinion).

If your patient with chronic kidney disease has been taking non-steroidal anti-inflammatory drugs, advise them to stop taking these when they are ill.

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

Treatment recommended for ALL patients in selected patient group

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.[645]
- The severity of symptoms of discontinuation may vary, but it may be unpleasant and may complicate the management of the acute medical condition.[646]
When reviewing current medication, look out for:
- Perceived 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 in 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.[645][647]Consider this issue for all medications prescribed in patients with COVID-19 as well as any experimental therapies (see the Emerging section).
- Drug-drug interactions and their associated adverse effects of particular relevance to patients with COVID-19 include sedation, cardiotoxicity (QT prolongation), and respiratory depression.[2]

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.
- Respiratory depression. Be aware that certain antidepressants may precipitate respiratory depression, especially when co-prescribed with other sedative drugs. Particular caution is needed with tricyclic antidepressants and mirtazapine.
- 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 the 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.[652]
  - 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.

If possible, ask the patient about non-pharmacological treatments for their depression and check 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.

Consider – experimental therapies

Treatment recommended for SOME patients in selected patient group

Take the patient’s comorbidities into account when considering experimental therapies

The World Health Organization (WHO) recommends that potential adverse effects and drug-drug interactions are considered in patients being treated for COVID-19.[2]

An important example of this, in a patient on medication for a comorbidity, is the use of a certain drug for COVID-19 that prolongs the QT interval when the patient is already prescribed another drug, for the comorbidity, that also causes QT prolongation. Considerable caution is required.

With this in mind, consider your patient’s medication and comorbidities.

The WHO has highlighted the following in its interim guidance on the clinical management of COVID-19 as important adverse effects of some of the experimental therapies:[2]
- Lopinavir/ritonavir: the most common adverse effects are gastrointestinal
- Umifenovir: diarrhoea, nausea
- Favipiravir: QT interval prolongation
- Interferon beta: pyrexia, rhabdomyolysis
- Tocilizumab: upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased alanine aminotransferase, injection-site reactions
- Hydroxychloroquine/chloroquine ± azithromycin: each can cause QT prolongation and taken together can increase the risk of cardiotoxicity.

Follow local drug protocol guidelines and consult senior colleagues prior to initiating any novel therapies. Certain drugs should only be used in the context of a clinical trial.

Consider adverse effects as well as possible drug-drug interactions in light of your patient’s comorbidities and symptoms.
This list of adverse effects is not exhaustive – consult local formulary for further information. Consult your colleagues from relevant specialties and/or a pharmacist for advice.

Consider – plan for discharge and rehabilitation

Treatment recommended for SOME patients in selected patient group

Routinely assess intensive care patients for mobility, functional swallow, cognitive impairment, and mental health concerns, and based on that assessment determine whether the patient is ready for discharge, and whether the patient has any rehabilitation and follow-up requirements.[2]

Ensure plans are in place for follow-up of comorbidities

Ensure the patient has follow-up plans in place concerning any comorbidities as well as discharge and follow-up criteria related to COVID-19.

Knowledge and experience concerning the rehabilitation needs of patients post-hospital discharge is still increasing.[674][675]
COVID-19 may have long-term effects that relate to other comorbidities. UK-based patients with certain comorbidities may find the following sources of information useful:
- Asthma UK and British Lung Foundation: post-COVID hub external link opens in a new window
- Diabetes UK: your safe discharge from hospital – an information leaflet for people with diabetes external link opens in a new window
Follow your local protocols and ask advice from relevant speciality teams.
Consider use of telemedicine to facilitate remote consultations in selected patients.[578][579]

Consider – palliative care

Plus – monitor comorbidities during hospital stay

– ensure monitoring is in place to detect any asthma exacerbation during the 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.[593][630]
See our topic Acute exacerbation of asthma in adults.
Temporarily stop any long-acting muscarinic receptor antagonist (LAMA) the patient may be on for maintenance therapy (e.g., tiotropium, aclidinium, glycopyrronium, umeclidinium) if you prescribe a nebulised 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 the 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, follow the patient’s personalised action plan.

Based on the limited evidence available, the Global Initiative for Chronic Obstructive Lung Disease recommends to follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[585][587][589][594]
See our topic Acute exacerbation of 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.

If a nebuliser is used, bronchodilator therapy via a nebuliser should only be used for 24 to 48 hours and then the patient should be switched back onto their usual inhaler(s).

Ensure to re-prescribe the LAMA once the nebuliser treatment has been stopped.

– 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 (pre-meal and before bedtime if eating) in any acutely unwell patient with diabetes mellitus.[632]

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

There is no consensus on target blood glucose levels for people with diabetes in hospital with an acute medical condition.

The UK Joint British Diabetes Societies for Inpatient Care (JBDS-IP) recommends an ideal range of 6 to 10 mmol/L (108-180 mg/dL), and an acceptable range of 4 to 12 mmol/L (72-216 mg/dL).[633]A more liberal blood glucose target is considered appropriate if your patient is at high risk of falls, is frail, or has dementia.[633]
- The UK-based National Inpatient Diabetes COVID-19 Response Group makes the same recommendation for patients in hospital with COVID-19.[634]
- Consensus guidance from an international group of experts recommends aiming for levels of between 4 and 10 mmol/L (72 and 180 mg/dL) in patients with COVID-19, but to adjust the lower level to 5 mmol/L (90 mg/dL) in patients who are frail.[611]
The American Diabetes Association recommends a target range of 7.8 to 10.0 mmol/L (140-180 mg/dL) for most critically and non-critically ill patients (not specifically with COVID-19).[632]

Data are still limited on blood glucose control and its association with outcomes for patients with COVID-19.[606]

Hyperglycaemia during the ongoing hospital admission

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.[606]
- Exclude DKA or HHS, both of which require specific urgent management.
- Consider other conditions associated with hyperglycaemia, such as sepsis.[605]
Be aware that the following medications may be associated with hyperglycaemia and may need to be reviewed:[635]
- 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., as a component in antiretroviral therapy, lopinavir/ritonavir may be used to treat some patients with COVID-19).
Some experimental drugs used in the management of COVID-19 may be associated with (or cause) hyperglycaemia. Check local drug formularies for further information before prescribing these therapies in patients with diabetes.
If your patient has persistently elevated blood glucose, they may need insulin therapy (intravenous or subcutaneous protocols). Follow your local protocols on management of hyperglycaemia in patients with COVID-19.
- Infusion pump devices may not be available outside of intensive care unit (ICU) settings, depending on the need for these devices elsewhere. In this situation, some protocols recommend alternative subcutaneous regimens when managing hyperglycaemia and mild DKA.[634][636]
- Be aware that patients with type 2 diabetes in ICU may have significant degrees of insulin resistance.[634]

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.

1 in 5 inpatients with diabetes in England and Wales have a hypoglycaemic episode during their hospital stay.[637]

Causes of hypoglycaemia include:[638]

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[634]
Accidental interruptions to patient feeding, which may occur especially when patients with COVID-19 are nursed in the prone position[634]
Reducing doses of corticosteroids, particularly dexamethasone in patients with COVID-19[634]
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.

Bedtime snacks can reduce the risk of early morning hypoglycaemia.[637]

Treat hypoglycaemia actively if the blood glucose falls below 4 mmol/L (72 mg/dL).[638]Follow hospital protocol. The JBDS-IP guidelines recommend that you:[638]

Retest blood glucose at 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.

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.[606]

– check the patient’s feet

Treatment recommended for ALL patients in selected patient group

A foot check is needed to detect new ulceration or infection, which may be unnoticed by the patient. It may even be the cause of their acute illness (e.g., patient presenting with sepsis, or endocarditis where the original focus of infection is the foot lesion).

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.[640]
- 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

Treatment recommended for ALL patients in selected patient group

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.[641]
- 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).
While data continue to emerge on the psychiatric impact of COVID-19, it is interesting to note that other severe coronavirus infections (severe acute respiratory syndrome [SARS] and Middle East respiratory syndrome [MERS]) have been found to be associated with low mood both in the acute phase of the illness as well as at follow-up.[642][643]
Consider other factors that may be influencing the patient’s mental state (e.g., the effect of any illicit drug use or alcohol).[644]

– consider referral to 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.[653][654]

Follow your local protocols/referral pathways in your hospital during the COVID-19 pandemic.

COVID-19 is associated with psychiatric and neurological manifestations including depression.[2]



Evidence: Depression and adherence with treatment

Comorbid depression is linked to poor adherence with recommended physical health treatments, from medication to rehabilitation.[655]

This may lead to worse clinical outcomes, including longer hospital stays.[646][656][657]
Most importantly, depression is linked with excess mortality.[658]

– manage nicotine dependence in current smokers

Treatment recommended for ALL patients in selected patient group

Nicotine replacement therapy prevents rapid withdrawal during admission, which can be distressing and uncomfortable.
- Preparations include transdermal patches or, for patients with skin allergies, inhalators, lozenges, gum, or sprays. Dose depends on how many cigarettes are smoked/day and the formulation chosen.
- Use with caution in haemodynamically unstable patients hospitalised with acute stroke, myocardial infarction, and/or uncontrolled hypertension and in patients with severe renal impairment.
- Monitor blood glucose closely if starting nicotine replacement therapy in patients with diabetes.
- Consult your local drug formulary and hospital guidance for more comprehensive details.

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Coronavirus disease 2019 (COVID-19)

Treatment algorithm

mild COVID-19

Comorbidities in pregnancy and in children

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

Check baseline kidney function and monitor closely

Support patients with known depression

NSAIDs in patients with chronic kidney disease, heart failure, or 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

People with type 1 diabetes

People with type 2 diabetes

Plus – monitor comorbidities during hospital stay

moderate COVID-19

Comorbidities in pregnancy and in children

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

Check baseline kidney function and monitor closely

Continue to monitor fluid balance particularly closely

Support patients with known depression

Management in the community setting

Management in the hospital setting

NSAIDs in patients with chronic kidney disease, heart failure, or 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

Plus – monitor comorbidities during hospital stay

Management of a patient with delirium

Hyperglycaemia during the ongoing hospital admission

Hypoglycaemia during the ongoing hospital admission

severe COVID-19

Comorbidities in pregnancy and in children

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

Baseline neurological assessment

Oxygen therapy in patients with asthma

Oxygen therapy in patients with COPD

Assess fluid status and manage fluid balance particularly closely

Baseline cognitive and delirium assessments with collateral history

Management of a patient with delirium

Mental state examination

Anticoagulation in patients with chronic kidney disease

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

Check baseline kidney function and monitor closely

Continue to monitor fluid balance particularly closely

Manage the patient’s diabetes when they are taking corticosteroids

Monitor for psychiatric complications of corticosteroids

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

Take the patient’s comorbidities into account when considering novel therapies

Primary options

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