Coronavirus disease 2019 (COVID-19)

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

ADD COMORBIDITIES TO THIS TREATMENT ALGORITHMomorbidities:

ACUTE

mild COVID-19

1st line – consider home isolation

Isolate 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 to contain virus transmission.[87]

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.[87][19]
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.[791]
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.[87]

Comorbidities in pregnancy and in children

The information in the BMJ Best Practice comorbidities manager 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 your patient has may affect your management of COVID-19.

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

Monitor patients with risk factors closely and consider the most appropriate setting of care, taking into account these risk factors.[897]

The World Health Organization lists the following comorbidities as risk factors for severe disease and death:[897]

Cardiac disease
Diabetes mellitus
Chronic lung disease
Chronic kidney disease
Cerebrovascular disease
Dementia
Mental disorders
Cancer
Immunosuppression
Obesity
Hypertension.

Older people and those with higher levels of frailty are reported in some studies to have an increased mortality risk with COVID-19.[897][898]

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

Multidisciplinary collaborative care is recommended for older people with COVID-19 to help ensure all aspects of care (including comorbidities) are adequately addressed.[897]

Advise patients and household members to follow appropriate infection prevention and control measures:

Guidance on when to stop isolation varies widely across locations.

Isolation periods may depend on various factors including vaccination status, circulating SARS-CoV-2 variants, and patient factors (e.g., immunocompetent/immunocompromised, asymptomatic/symptomatic, disease severity).
The World Health Organization recommends discontinuing transmission-based precautions (including isolation) and releasing patients from the care pathway 10 days after positive test (asymptomatic patients), or 10 days after symptom onset plus at least 3 days without fever and respiratory symptoms (symptomatic patients).[87]
However, some countries now recommend isolation periods as short as 5 days to 7 days.[789]
Consult your local public health guidance for more information.

Plus – monitor comorbidities during hospital stay

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).[87][19]

Pulse oximetry monitoring at home is recommended in symptomatic patients with risk factors for progression to severe disease who are not hospitalised. Patient education and appropriate follow-up are required.[87]

Check baseline kidney function and monitor closely

Check baseline kidney function and monitor particularly closely if your patient has a history of CKD.[899]

CKD is a significant risk factor for acute kidney injury (AKI).[900]
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.
- AKI in patients with COVID-19 may be common (although exact prevalence is uncertain). AKI is associated with increased mortality.[901] See Complications.
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.[897]

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

For patients with CKD:
- Compare kidney function with last available results, and follow local protocol for detecting AKI
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion)
- Monitor for and respond to oliguria.[899]

Plus – monitor comorbidities during hospital stay

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 first (e.g., a teaspoon of honey in patients aged 1 year and older) to help cough.[20]

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.[792]

Advise patients about adequate nutrition and appropriate rehydration.

Advise patients to drink fluids regularly to avoid dehydration. Fluid intake needs can be higher than usual because of fever. However, too much fluid can worsen oxygenation.[87][20]

Other supportive care measures include:

Advise patients to improve air circulation by opening a window or door[20]
Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate[87]
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.[793] A Cochrane review found there is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following infection. The only evidence available is for intranasal corticosteroids, and this is of very low certainty, so no conclusions could be drawn.[794]

Most children with mild disease can be managed with supportive care alone.[19]

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.[902]
Consider use of telemedicine to facilitate remote consultations.[897][903][904] Royal College of Psychiatrists: digital - COVID-19 guidance for clinicians Opens in new window
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 Opens in new window

Plus – monitor comorbidities during hospital stay

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:[905]
- 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 advance care planning, including legally binding advanced directives.[897][905]

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).[906] Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[907] Assessments should follow the principles in the Act.[907]
If a patient is assessed to lack mental capacity, ensure decisions are made in the best interests of the patient.[906][907]

If the patient is assessed to lack mental capacity, consult with next of kin to make ‘best interests’ decisions.[907]

According to the 2005 Mental Capacity Act in England and Wales, if a patient has no family members or other carers and a decision is not urgent, you should seek an independent mental capacity advocate to perform this role.[908]
Check the appropriate legislation for your territory.

Plus – monitor comorbidities during hospital stay

Consider – antipyretic/analgesic

Treatment recommended for SOME patients in selected patient group

Paracetamol or ibuprofen are recommended.[87][20]

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

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

Chronic kidney disease and/or heart failure

Avoid non-steroidal anti-inflammatory drugs (NSAIDs) in your patient with heart failure (based on expert opinion) and/or with chronic kidney disease.[899]

Asthma

NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[909]

Primary options

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

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

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

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

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

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

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

Show drug information for a patient with no comorbidities

Primary options

paracetamol

For patients with CKD, please check your local drug formulary

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

ibuprofen

For patients with CKD, please check your local drug formulary

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

Plus – monitor comorbidities during hospital stay

Consider – monoclonal antibody

Treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations for the use of casirivimab/imdevimab in patients with COVID-19BMJ. 2020;370:m3379 [Citation ends].

Consider a monoclonal antibody. Options may include sotrovimab, casirivimab/imdevimab, bamlanivimab/etesevimab, bebtelovimab, and regdanvimab, depending on your location. Guideline recommendations vary.

The World Health Organization recommends sotrovimab or casirivimab/imdevimab for patients with non-severe disease who are at highest risk of hospitalisation. Casirivimab/imdevimab should only be used where viral genotyping can confirm a susceptible SARS-CoV-2 variant (i.e., excluding Omicron). Monoclonal antibodies probably reduce the risk of hospitalisation and duration of symptoms in patients with non-severe disease, based on moderate-certainty evidence. While monoclonal antibodies achieve a substantial reduction in the relative risk of hospitalisation, the absolute benefit will be trivial or unimportant in absolute terms for all but those who are at highest risk of disease (e.g., unvaccinated, older people, immunodeficiencies, and/or chronic disease). Treatment is in addition to the current standard of care. The applicability of this recommendation to children is currently uncertain.[21][787][788]
In the UK, the National Institute for Health and Care Excellence recommends offering a neutralising monoclonal antibody to patients ≥12 years of age who are not in hospital and are thought to be at high risk of progression to severe disease. Consult local guidance for monoclonal antibodies with current UK access.[20]
In the US, the National Institutes of Health guidelines panel recommends bebtelovimab for the treatment of non-hospitalised patients with mild to moderate disease who are at high risk of clinical progression. However, it is only recommended when preferred therapies (i.e., antivirals) are not available, feasible to use, or clinically appropriate as it has not been evaluated in patients at high risk of progression in placebo-controlled trials. Use may be considered in patients with mild to moderate disease who are hospitalised for a reason other than COVID-19 provided that they otherwise meet the criteria for outpatient treatment. The panel currently recommends against the use of casirivimab/imdevimab, bamlanivimab/etesevimab, and sotrovimab because Omicron is the dominant variant in the US, and these monoclonal antibodies are predicted to have markedly reduced susceptibility to Omicron and its subvariants.[19] These monoclonal antibodies are not currently authorised for use in the US.[795][796]
The Infectious Diseases Society of America supports the use of monoclonal antibodies in ambulatory patients with mild to moderate disease who are at high risk for progression to severe disease, although it only recommends bebtelovimab in the context of a clinical trial.[510]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Choice of monoclonal antibody depends on availability, as well as clinical and contextual factors including emerging information about efficacy with different variants.[19][20][21]

Preclinical evidence has emerged suggesting that casirivimab/imdevimab and bamlanivimab/etesevimab lack neutralisation activity against the Omicron variant in vitro. Sotrovimab and bebtelovimab appear to retain activity against Omicron; however, sotrovimab is not active against the Omicron BA.2 subvariant. Consult local guidance for details regarding specific variants and resistance.
Logistical or supply constraints may make patient triage necessary. Treatment should be prioritised for patients who are at the highest risk of progressing to severe disease.

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

A Cochrane review found that the evidence is insufficient to draw meaningful conclusions about any specific monoclonal antibody, and the disease stage in which it should be used. Information on outcomes in non-hospitalised patients such as mortality, quality of life, and serious adverse events is either inconclusive or entirely lacking, although casirivimab/imdevimab, sotrovimab, bamlanivimab (alone or in combination with etesevimab), and regdanvimab may reduce the occurrence of hospital admission or death (low-certainty evidence).[798]

Monoclonal antibodies are administered by intravenous infusion.

Casirivimab/imdevimab is also available in a subcutaneous formulation, but intravenous administration is recommended. However, if intravenous infusions are not feasible or would cause a delay in treatment, subcutaneous administration may be considered.[19] Evidence for subcutaneous administration is emerging.[797]
Outpatient administration in specialised clinics is required, which may limit the feasibility of these treatments.[21]
Administer as soon as possible after a positive test and within 7 days of symptom onset.[19]
Dose varies across guidelines; consult local protocols.

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

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

Primary options

sotrovimab: children ≥12 years of age and adults: consult specialist for guidance on dose

sotrovimab : children ≥12 years of age and adults: consult specialist for guidance on dose

sotrovimab: children ≥12 years of age and adults: consult specialist for guidance on dose

casirivimab and imdevimab: children ≥12 years of age and adults: consult specialist for guidance on dose

casirivimab and imdevimab : children ≥12 years of age and adults: consult specialist for guidance on dose

casirivimab and imdevimab: children ≥12 years of age and adults: consult specialist for guidance on dose

bebtelovimab: children ≥12 years of age and adults: consult specialist for guidance on dose

bebtelovimab : children ≥12 years of age and adults: consult specialist for guidance on dose

bebtelovimab: children ≥12 years of age and adults: consult specialist for guidance on dose

bamlanivimab: children and adults: consult specialist for guidance on dose (administered with etesevimab)

bamlanivimab : children and adults: consult specialist for guidance on dose (administered with etesevimab)

bamlanivimab: children and adults: consult specialist for guidance on dose (administered with etesevimab)

Plus – monitor comorbidities during hospital stay

Consider – antiviral

Treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations and evidence for the use of remdesivir in hospitalised patients with COVID-19BMJ. 2020;370:m3379 [Citation ends].

Consider the antiviral agent remdesivir. Guideline recommendations vary.

The World Health Organization conditionally recommends remdesivir for patients ≥12 years of age (weighing ≥40 kg) with non-severe disease who are at highest risk of hospitalisation.[21][787][788]
In the UK, the National Institute for Health and Care Excellence recommends remdesivir for patients ≥12 years of age (weighing ≥40 kg) who do not need supplemental oxygen, and are within 7 days of symptom onset, and are thought to be at high risk of progression to severe disease (based on low-certainty evidence).[20]
In the US, the National Institutes of Health guidelines panel recommends remdesivir to treat non-hospitalised patients with mild to moderate disease who are at high risk of clinical progression.[19] Remdesivir is approved in paediatric patients ≥28 days of age (weighing at least 3 kg [7 lbs]) in the US.[799]
The Infectious Diseases Society of America supports the use of remdesivir in ambulatory patients with mild to moderate disease who are at high risk for progression to severe disease.[510]

Remdesivir should be initiated as soon as possible, ideally within 7 days of symptom onset.[19][20][21]

The treatment course for this indication is 3 days. If a patient requires hospitalisation after starting treatment, the full treatment course can be completed at the healthcare provider’s discretion.
Logistical constraints may make it difficult to administer the drug in some outpatient settings as it requires administration via intravenous infusion. Renal and/or hepatic monitoring may be required.

Adverse effects include nephrotoxicity and hepatotoxicity.

Remdesivir is not recommended in patients with an estimated glomerular filtration rate <30 mL/minute. Monitor renal function before starting treatment and during treatment as clinically appropriate. Intravenous formulations contain the solubility enhancer sulfobutyl ether beta-cyclodextrin sodium (SBECD), which is renally cleared. Accumulation of SBECD in patients with renal impairment may result in liver and renal toxicities. Consider preferential use of the lyophilised powder formulation in patients with renal impairment if available, as it contains less SBECD.
Remdesivir may have little or no effect on acute kidney injury compared with placebo; however, the certainty of evidence is low.[910]
Transaminase elevations have been reported. Monitor liver function before starting treatment and during treatment as clinically appropriate. Consider discontinuing treatment if alanine aminotransferase (ALT) levels increase to ≥10 times the upper limit of normal. Discontinue treatment if ALT elevation is accompanied by signs or symptoms of liver inflammation.
Monitor prothrombin time before starting treatment and during treatment as clinically appropriate as increases in prothrombin time have been reported.

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

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

Evidence for this indication is emerging.

Remdesivir probably reduces hospital admission (moderate-certainty evidence), and may have little or no impact on mortality (low-certainty evidence). The effect on mechanical ventilation and time to symptom resolution is very uncertain. The balance between benefits and potential harms favours treatment, but only in the highest risk group.[21][787][788]
A randomised, double-blind, placebo-controlled trial of 562 patients found that a 3-day course of remdesivir resulted in an 87% lower risk of hospitalisation or death among non-hospitalised patients who were at high risk for disease progression compared with placebo. The most common co-existing conditions were diabetes, obesity, and hypertension.[800]

Logistical or supply constraints may make patient triage for antiviral treatment necessary.

Therapy should be prioritised for patients who are at the highest risk of progressing to severe disease.

Oral antiviral agents (e.g., molnupiravir, nirmatrelvir/ritonavir) are also available and may be recommended.

The World Health Organization states that nirmaltrelvir/ritonavir may represent a superior choice to remdesivir (and monoclonal antibodies).[21][787][788] See the Emerging section for more information on oral antiviral agents.

Take your patient’s kidney function into account when considering remdesivir

Check kidney function before starting remdesivir in your patient with CKD, as you would with any patient.[911]

Remdesivir is contraindicated if your patient has an estimated glomerular filtration rate (eGFR) <30 mL/minute.[911]
Consider preferential use of the lyophilised powder formulation in patients with renal impairment if available, as it contains less sulfobutyl ether beta-cyclodextrin sodium (SBECD), which is renally cleared.[911]
Consult your local protocol and seek advice from the nephrology team. Guidelines vary on recommendations for remdesivir.

Primary options

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

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

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

Plus – monitor comorbidities during hospital stay

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

Treatment recommended for ALL patients in selected patient group

Guidelines from several professional respiratory organisations agree that patients with asthma or COPD should be advised to continue to take their inhalers as prescribed (including inhaled corticosteroids), whether they do or do not also have COVID-19.[912][913][914][915][916]

The overall aim for continuing inhaled corticosteroids is to reduce the risk of an exacerbation of asthma or COPD.[916]
There is no evidence that inhaled corticosteroids are related to COVID-19 infection in people with asthma.[917] There is also no evidence they increase the risks associated with COVID-19 in people with COPD.[915]

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.[912][915][918]
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.[918]

Advise patients with COPD not to start oral corticosteroids and/or antibiotics for symptoms of COVID-19, such as fever, myalgia, and dry cough.[915]

Patients with COPD and COVID-19 should receive the same standard-of-care treatments for COVID-19 as for those without a diagnosis of COPD.[914]

Plus – monitor comorbidities during hospital stay

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.[913]

Follow established guidelines if asthma worsens, and consider hospital admission. Start oral corticosteroids as indicated for asthma exacerbations.[916][919][920]
Ensure safety netting measures are in place in case the patient does not improve or the situation changes.[919]

Practical tip

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.[913] Advise your patient with known COVID-19 to seek medical advice if there is a deterioration in symptoms.

Plus – monitor comorbidities during hospital stay

Plus – ensure plans are in place to manage any COPD exacerbation

Treatment recommended for ALL patients in selected patient group

If an exacerbation of COPD is suspected in a patient with mild COVID-19 and pre-existing COPD, follow the patient’s personalised action plan. If your patient is at home, ensure they know to seek medical advice.[915]

Follow established guidelines on the management of an exacerbation of COPD, including prescription of short-term oral corticosteroids if clinically indicated.[914][916] Seek specialist advice and consider hospital admission.
- The standard recommended length of course for oral corticosteroids if prescribed for exacerbation of COPD is 5 days only.[921][922]
Differentiate from other conditions, such as acute coronary syndrome, acute heart failure, and pneumonia, as well as from complications of COVID-19.
See our topic Acute exacerbation of COPD.

Plus – monitor comorbidities during hospital stay

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.[897]

Despite concern about the possible increased risk of infection or more severe disease in patients prescribed ACE inhibitors or angiotensin-II receptor antagonists, moderate- to high-certainty evidence has found that the use of these drugs is not associated with severe disease or poor outcomes.[923][924][925]
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.[926][927][928][929]

The UK Kidney 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.[928][929][930] 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 ill (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(based on expert opinion).

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

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

Plus – monitor comorbidities during hospital stay

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

Treatment recommended for ALL patients in selected patient group

If your patient with diabetes has mild COVID-19 and you consider them well enough to stay at home:

Advise them to follow sick-day rules from their individual healthcare provider or relevant national or regional professional diabetes organisation[931][932][933][934][935][936]
Despite limited evidence for this situation, diabetes self-management during illness with COVID-19 generally still follows the standard sick-day rules.[937] Provide an individualised written management plan.[936]

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

Practical tip

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

Key general points for all patients with diabetes

Recommendations include to:[933][934]

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

Practical tip

Be aware that blood glucose can increase during illness even when not eating. People who are ill with COVID-19 appear to have an even greater risk of developing hyperglycaemia with ketones, including those with type 2 diabetes (especially if they are taking a sodium-glucose cotransporter-2 (SGLT-2) inhibitor).[938]

People with type 1 diabetes

In addition to the general points above, make sure that during any acute illness patients with type 1 diabetes are aware of the need to:[934]

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

Most COVID-related consensus statements recommend SGLT-2 inhibitors (e.g., dapagliflozin, canagliflozin, empagliflozin) should be stopped during acute illness.[939] These drugs are not approved for use in type 1 diabetes in the UK, but rarely patients may be taking these drugs on specialist advice.

If your patient usually takes this medication, advise them to test their blood for ketones even if their blood glucose is not elevated.[938]
Patients on SGLT-2 inhibitors are at risk of euglycaemic ketoacidosis.[940][941] 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.[939][942] They are at risk of euglycaemic ketoacidosis with SGLT-2 inhibitors and should check for blood ketones even once this medication is stopped.[940][941] This may be something the patient is not familiar with doing, so organise this to be done urgently.
- Patients who usually take metformin are also advised, in most COVID-related consensus statements, to stop this medication during acute illness.[939][942] 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.[942] On the other hand, during illness, some patients may develop hyperglycaemia so may need to temporarily increase their dose. Blood glucose monitoring is crucial to guide these decisions.

Sick-day rules from the UK NHS also recommend that patients stop glucagon-like peptide-1 (GLP-1) agonists (e.g., dulaglutide, exenatide, liraglutide, lixisenatide).[942]

Practical tip

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

Isolate patients with suspected or confirmed moderate disease (i.e., clinical signs of pneumonia but no signs of severe pneumonia) to contain virus transmission.[87]

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.[87][19]

Comorbidities in pregnancy and in children

The information in the BMJ Best Practice comorbidities manager 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 your patient has may affect your management of COVID-19.

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

Monitor patients with risk factors closely and consider the most appropriate setting of care, taking into account these risk factors.[897]

The World Health Organization lists the following comorbidities as risk factors for severe disease and death:[897]

Cardiac disease
Diabetes mellitus
Chronic lung disease
Chronic kidney disease
Cerebrovascular disease
Dementia
Mental disorders
Cancer
Immunosuppression
Obesity
Hypertension.

Older people and those with higher levels of frailty are reported in some studies to have an increased mortality risk with COVID-19.[897][898]

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

Multidisciplinary collaborative care is recommended for older people with COVID-19 to help ensure all aspects of care (including comorbidities) are adequately addressed.[897]

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:

Guidance on when to stop isolation varies widely across locations.

Isolation periods may depend on various factors including vaccination status, circulating SARS-CoV-2 variants, and patient factors (e.g., immunocompetent/immunocompromised, asymptomatic/symptomatic, disease severity).
The World Health Organization recommends discontinuing transmission-based precautions (including isolation) and releasing patients from the care pathway 10 days after positive test (asymptomatic patients), or 10 days after symptom onset plus at least 3 days without fever and respiratory symptoms (symptomatic patients).[87]
However, some countries now recommend isolation periods as short as 5 days to 7 days.[789]
Consult your local public health guidance for more information.

Plus – monitor comorbidities during hospital stay

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).[87][19]

Pulse oximetry monitoring at home is recommended in symptomatic patients with risk factors for progression to severe disease who are not hospitalised. Patient education and appropriate follow-up are required.[87]
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.[87]

Check baseline kidney function and monitor closely

Check baseline kidney function and monitor particularly closely if your patient has a history of CKD.[899]

CKD is a significant risk factor for acute kidney injury (AKI).[900]
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.
- AKI in patients with COVID-19 may be common (although exact prevalence is uncertain). AKI is associated with increased mortality.[901] See Complications.
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.[897]

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

For patients with CKD:
- Compare kidney function with last available results, and follow local protocol for detecting AKI
- Monitor kidney function daily, along with careful volume status monitoring (based on expert opinion)
- Monitor for and respond to oliguria.[899]

Plus – monitor comorbidities during hospital stay

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 first (e.g., a teaspoon of honey in patients aged 1 year and older) to help cough.[20]

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.[792]

Advise patients about adequate nutrition and appropriate rehydration.

Advise patients to drink fluids regularly to avoid dehydration. Fluid intake needs can be higher than usual because of fever. However, too much fluid can worsen oxygenation.[87][20]

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.[901] Seek senior advice, particularly for complex patients, such as those with heart failure and/or CKD.

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:
- 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.[943]

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.

Other supportive care measures include:

Advise patients to improve air circulation by opening a window or door[20]
Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate[87]
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.[793] A Cochrane review found there is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following infection. The only evidence available is for intranasal corticosteroids, and this is of very low certainty, so no conclusions could be drawn.[794]

Most children with moderate disease can be managed with supportive care alone.[19]

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.[902]
Consider use of telemedicine to facilitate remote consultations.[897][903][904] Royal College of Psychiatrists: digital - COVID-19 guidance for clinicians Opens in new window
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 Opens in new window

Plus – monitor comorbidities during hospital stay

Consider – antibiotics

Treatment recommended for SOME patients in selected patient group

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

Start treatment as soon as possible, and refer to local guidelines for choice of regimen.[87][19][20] The regimen should be based on the clinical diagnosis, local epidemiology and susceptibility data, and local treatment guidelines.
Antibiotics may also be considered in older people (particularly those in long-term care facilities) and children <5 years of age to provide empirical antibiotic treatment for possible pneumonia.[87]
Do not offer an antibiotic for preventing secondary bacterial pneumonia in people with COVID-19.[20]

Advise patients to seek medical help without delay if their symptoms do not improve, or worsen rapidly or significantly.

Reconsider whether the person has signs and symptoms of more severe disease on reassessment, and whether to refer them to hospital, other acute community support services, or palliative care services.[20]

Plus – monitor comorbidities during hospital stay

Consider – antipyretic/analgesic

Treatment recommended for SOME patients in selected patient group

Paracetamol or ibuprofen are recommended.[87][20]

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

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

Chronic kidney disease and/or heart failure

Avoid non-steroidal anti-inflammatory drugs (NSAIDs) in your patient with heart failure (based on expert opinion) and/or with chronic kidney disease.[899]

Asthma

NSAIDs can worsen symptoms in some patients with asthma, so check whether your patient has a known sensitivity.[909]

Primary options

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

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

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

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

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

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

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

Show drug information for a patient with no comorbidities

Primary options

paracetamol

For patients with CKD, please check your local drug formulary

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

ibuprofen

For patients with CKD, please check your local drug formulary

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

Plus – monitor comorbidities during hospital stay

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:[905]
- 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 advance care planning, including legally binding advanced directives.[897][905]

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).[906] Follow the appropriate legislation in your region.
In England and Wales, health professionals must comply with the 2005 Mental Capacity Act.[907] Assessments should follow the principles in the Act.[907]
If a patient is assessed to lack mental capacity, ensure decisions are made in the best interests of the patient.[906][907]

If the patient is assessed to lack mental capacity, consult with next of kin to make ‘best interests’ decisions.[907]

According to the 2005 Mental Capacity Act in England and Wales, if a patient has no family members or other carers and a decision is not urgent, you should seek an independent mental capacity advocate to perform this role.[908]
Check the appropriate legislation for your territory.

Plus – monitor comorbidities during hospital stay

Plus – monitor and manage diabetes

Plus – monitor comorbidities during hospital stay

Consider – monoclonal antibody

Treatment recommended for SOME patients in selected patient group

[Figure caption and citation for the preceding image starts]: Recommendations for the use of casirivimab/imdevimab in patients with COVID-19BMJ. 2020;370:m3379 [Citation ends].

The World Health Organization recommends sotrovimab or casirivimab/imdevimab for patients with non-severe disease who are at highest risk of hospitalisation. Casirivimab/imdevimab should only be used where viral genotyping can confirm a susceptible SARS-CoV-2 variant (i.e., excluding Omicron). Monoclonal antibodies probably reduce the risk of hospitalisation and duration of symptoms in patients with non-severe disease, based on moderate-certainty evidence. While monoclonal antibodies achieve a substantial reduction in the relative risk of hospitalisation, the absolute benefit will be trivial or unimportant in absolute terms for all but those who are at highest risk of disease (e.g., unvaccinated, older people, immunodeficiencies, and/or chronic disease). Treatment is in addition to the current standard of care. The applicability of this recommendation to children is currently uncertain.[21][787][788]
In the UK, the National Institute for Health and Care Excellence recommends offering a neutralising monoclonal antibody to patients ≥12 years of age who are not in hospital and are thought to be at high risk of progression to severe disease. Consult local guidance for monoclonal antibodies with current UK access.[20]
In the US, the National Institutes of Health guidelines panel recommends bebtelovimab for the treatment of non-hospitalised patients with mild to moderate disease who are at high risk of clinical progression. However, it is only recommended when preferred therapies (i.e., antivirals) are not available, feasible to use, or clinically appropriate as it has not been evaluated in patients at high risk of progression in placebo-controlled trials. Use may be considered in patients with mild to moderate disease who are hospitalised for a reason other than COVID-19 provided that they otherwise meet the criteria for outpatient treatment. The panel currently recommends against the use of casirivimab/imdevimab, bamlanivimab/etesevimab, and sotrovimab because Omicron is the dominant variant in the US, and these monoclonal antibody combinations are predicted to have markedly reduced susceptibility to Omicron and its subvariants.[19] These monoclonal antibodies are not currently authorised for use in the US.[795][796]
The Infectious Diseases Society of America supports the use of monoclonal antibodies in ambulatory patients with mild to moderate disease who are at high risk for progression to severe disease, although it only recommends bebtelovimab in the context of a clinical trial.[510]
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window

Choice of monoclonal antibody depends on availability, as well as clinical and contextual factors including emerging information about efficacy with different variants.[19][20][21]

Preclinical evidence has emerged suggesting that casirivimab/imdevimab and bamlanivimab/etesevimab lack neutralisation activity against the Omicron variant in vitro. Sotrovimab and bebtelovimab appear to retain activity against Omicron; however, sotrovimab is not active against the Omicron BA.2 subvariant. Consult local guidance for details regarding specific variants and resistance.
Logistical or supply constraints may make patient triage necessary. Treatment should be prioritised for patients who are at the highest risk of progressing to severe disease.

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

A Cochrane review found that the evidence is insufficient to draw meaningful conclusions about any specific monoclonal antibody, and the disease stage in which it should be used. Information on outcomes in non-hospitalised patients such as mortality, quality of life, and serious adverse events is either inconclusive or entirely lacking, although casirivimab/imdevimab, sotrovimab, bamlanivimab (alone or in combination with etesevimab), and regdanvimab may reduce the occurrence of hospital admission or death (low-certainty evidence).[798]

Monoclonal antibodies are administered by intravenous infusion.

Casirivimab/imdevimab is also available in a subcutaneous formulation, but intravenous administration is recommended. However, if intravenous infusions are not feasible or would cause a delay in treatment, subcutaneous administration may be considered.[19] Evidence for subcutaneous administration is emerging.[797]
Outpatient administration in specialised clinics is required, which may limit the feasibility of these treatments.[21]
Administer as soon as possible after a positive test and within 7 days of symptom onset.
Dose varies across guidelines; consult local protocols.

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

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