Recommendations

Key Recommendations

Management predominantly depends on disease severity, and focuses on the following principles: isolation at a suitable location; infection prevention and control measures; symptom management; optimised supportive care; and organ support in severe or critical illness.

Consider whether the patient can be managed at home. Generally, patients with asymptomatic or mild disease can be managed at home or in a community facility.[2]

Admit patients with moderate or severe disease to an appropriate healthcare facility. Assess adults for frailty on admission. Patients with critical disease require intensive care; involve the critical care team in discussions about admission to critical care when necessary. Monitor patients closely for signs of disease progression.[2][593]

Provide symptom relief as necessary. This may include treatments for fever, cough, breathlessness, anxiety, delirium, or agitation.[2][594]

Start supportive care according to the clinical presentation. This might include oxygen therapy, intravenous fluids, venous thromboembolism prophylaxis, high-flow nasal oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. Sepsis and septic shock should be managed according to local protocols.[2]

Consider empirical antibiotics if there is clinical suspicion of bacterial infection. Antibiotics may be required in patients with moderate, severe, or critical disease. Give within 1 hour of initial assessment for patients with suspected sepsis or if the patient meets high-risk criteria. Base the regimen on the clinical diagnosis, local epidemiology and susceptibility data, and local treatment guidelines.[2][561]

Consider systemic corticosteroid therapy for 7 to 10 days in adults with severe or critical disease. Moderate-quality evidence suggests that systemic corticosteroids probably reduce 28-day mortality in patients with severe and critical disease, and probably reduce the need for invasive ventilation.[3][593][595]

Assess whether the patient requires any rehabilitation or follow-up after discharge. 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]

Full recommendations

The decision about location of care depends on various factors including clinical presentation, disease severity, need for supportive care, presence of risk factors for severe disease, and conditions at home (including the presence of vulnerable people). Make the decision on a case-by-case basis using the following general principles.[2]

  • Mild disease: manage in a healthcare facility, in a community facility, or at home. Home isolation can be considered in most patients, including asymptomatic patients.

  • Moderate disease: manage in a healthcare facility, in a community facility, or at home. Home isolation can be considered in low-risk patients (i.e., patients who are not at high risk of deterioration).

  • Severe disease: manage in an appropriate healthcare facility.

  • Critical disease: manage in an intensive/critical care unit.

The location of care will also depend on guidance from local health authorities and available resources. Forced quarantine orders are being used in some countries.

Manage people who require hospitalisation and who are at risk of being infected with a SARS-CoV-2 variant of concern in a single room with en-suite bathroom facilities and appropriate infection control procedures for the duration of their isolation period. In those who test positive, discuss further risk assessment and appropriate case management with the local/regional specialist infectious diseases centre.[187]

The strongest risk factors for hospital admission are older age (odds ratio of >2 for all age groups older than 44 years, and odds ratio of 37.9 for people aged 75 years and over), heart failure, male sex, chronic kidney disease, and increased body mass index (BMI).[596] The median time from onset of symptoms to hospital admission is around 7 days.[46][516]

Children are less likely to require hospitalisation but, if admitted, generally only require supportive care.[21][597] Risk factors for intensive care admission in children include age <1 month, male sex, pre-existing medical conditions, and presence of lower respiratory tract infection signs or symptoms at presentation.[598] The majority of children who require ventilation have underlying comorbidities, most commonly cardiac disease.[599] Children with COVID-19 are reported to have similar hospitalisation rates, intensive care admission rates, and mechanical ventilator use compared with those with seasonal influenza.[576]

Overall, 19% of hospitalised patients require non-invasive ventilation, 17% require intensive care, 9% require invasive ventilation, and 2% require extracorporeal membrane oxygenation.[517] The rate of intensive care admission varies between studies; however, a meta-analysis of nearly 25,000 patients found that the admission rate was 32%, and the pooled prevalence of mortality in patients in the intensive care unit was 39%.[600] Another more recent meta-analysis found the mortality rate in patients in the intensive care unit to be 35.5%.[601] The most common reasons for intensive care unit admission are hypoxaemic respiratory failure leading to mechanical ventilation and hypotension.[602] Patients admitted to intensive care units were older, were predominantly male, and had a median length of stay of 23 days (range 12 to 32 days).[603] The strongest risk factors for critical illness are oxygen saturation <88%; elevated serum troponin, C-reactive protein, and D-dimer; and, to a lesser extent, older age, BMI >40, heart failure, and male sex.[596] The most common risk factors for intensive care unit mortality were invasive mechanical ventilation, acute kidney injury, and acute respiratory distress syndrome.[604]

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]

Location of care

  • 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.[583]

Isolation period

  • 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 (or up to 20 days in patients who are 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 home isolation once at least 10 days have passed since the date of a positive test. For severely immunocompromised patients who are asymptomatic, isolation may be discontinued when at least 10 days and up to 20 days have passed since the date of a positive test; consider consultation with infectious diseases specialists and infection control experts. Alternatively, the CDC 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; however, a test-based strategy can be considered in severely immunocompromised patients.[605] If the patient is hospitalised, the 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 self-isolation period is 10 days in patients with milder disease who are managed in the community.[606]

Infection prevention and control

Symptom management

  • Fever and pain: paracetamol or ibuprofen are recommended.[2][594] 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.[2][594][607][608][609][610][611][612][613] Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms.

  • 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.[594] 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.[614]

  • Olfactory dysfunction: consider treatment (e.g., olfactory training) if olfactory dysfunction persists beyond 2 weeks. Often it improves spontaneously and does not require specific treatment. There is no evidence to support the use of treatments in patients with COVID-19.[615]

Supportive care

  • 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).[594]

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

Monitor

  • 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]

  • 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.[2]

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]

Location of care

  • 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 in a healthcare facility.[2][3]

Isolation period

  • 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 CDC recommends discontinuing isolation once at least 10 days (not severely immunocompromised) or up to 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 up to 20 days (severely immunocompromised) have passed since the date of a positive test. Severely immunocompromised patients may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts before discontinuing isolation. Alternatively, the CDC recommends at least two negative 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; however, a test-based strategy can be considered in severely immunocompromised patients.[616] If the patient is isolated at home, the 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. Immunocompetent patients who tested positive on RT-PCR and have completed their 14-day isolation period are exempt from testing prior to hospital discharge if they are within 90 days from their initial illness onset or test, unless they develop new symptoms.[606]

Infection prevention and control

  • 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 (see above).

Symptom management and supportive care

  • Manage symptoms and provide supportive care as appropriate (see above).

Antibiotics

  • Consider empirical antibiotics if there is clinical suspicion of bacterial infection.[2][3] 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.[2]

Monitor

  • 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). 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.[2]

  • 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]

Corticosteroids

  • The WHO does not recommend corticosteroids in patients with non-severe disease as they may increase the risk of mortality in these patients.[595] In the UK, NHS England supports these guidelines, and does not recommend the use of corticosteroids in patients with non-severe COVID-19.[617] In the US, the National Institutes of Health guidelines panel recommends against the use of corticosteroids in non-hospitalised patients with mild to moderate disease.[3]

Patients with suspected or confirmed severe disease are at risk of rapid clinical deterioration.[2]

  • 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

    • 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 signs: inability to breastfeed or drink, lethargy or unconsciousness, or convulsions

    • Fast breathing (<2 months: ≥60 breaths per minute; 2-11 months: ≥50 breaths per minute; 1-5 years: ≥40 breaths per minute).

Location of care

  • Manage patients in an appropriate healthcare facility under the guidance of a specialist team.[2]

  • 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 A meta-analysis found that an increase in CFS was associated with an increase in mortality (each 1-point increase in CFS was associated with a 12% increase in mortality).[618] However, some studies suggest that a more nuanced understanding of frailty and outcomes is needed, and you should exercise caution in placing too much emphasis on the influence of frailty alone when discussing prognosis in older people.[619]

  • Involve critical care teams in discussions about admission to critical care for patients where:

    • The CFS score suggests the person is less frail (e.g., CFS <5), they are likely to benefit from critical care organ support, and the patient wants critical care treatment; or

    • The CFS score suggests the person is more frail (e.g., CFS ≥5), there is uncertainty regarding the benefit of critical care organ support, and critical care advice is needed to help the decision about treatment.

  • Take into account the impact of underlying pathologies, comorbidities, and severity of acute illness.[593]

Isolation period

  • 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 CDC recommends discontinuing isolation once at least 10 days and up to 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. Consider consultation with infection control experts before discontinuing isolation. Severely immunocompromised patients may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts before discontinuing isolation. Alternatively, the CDC recommends at least two negative 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; however, a test-based strategy can be considered in severely immunocompromised patients.[616]

  • 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. Immunocompetent patients who tested positive on RT-PCR and have completed their 14-day isolation period are exempt from testing prior to hospital discharge if they are within 90 days from their initial illness onset or test, unless they develop new symptoms.[606]

Infection prevention and control

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

Oxygen

  • 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] There is no evidence of benefit for oxygen therapy in patients with COVID-19 in the absence of hypoxaemia.[620]

  • 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%.[621]

  • 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 96% (or 90% to 94% if clinically appropriate), for example.[622]

  • Consider positioning techniques (e.g., high supported sitting), and airway clearance management to optimise oxygenation assist with secretion clearance in adults. Consider awake prone positioning (for 8-12 hours/day, broken into shorter periods over the day) in severely ill patients who require supplemental oxygen.[2][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.[623][624][625][626][627]

  • Monitor patients closely for signs of progressive acute hypoxaemic respiratory failure. Patients who continue to deteriorate despite standard oxygen therapy require advanced oxygen/ventilatory support.[2][3]

Symptom management and supportive care

  • 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.[628]

  • Fever and pain: paracetamol or ibuprofen are recommended.[2][594] 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.[607][608][609][610][611][612][613] Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms.

  • 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.[594] 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.[614]

  • 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.[594]

  • 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][594] 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.[594] 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.[629]

  • 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.[630]

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

Venous thromboembolism prophylaxis

  • Assess the risk of bleeding as soon as possible after admission, or by the time of the first consultant review, using a suitable risk assessment tool.[631]

  • 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][632][633] Start as soon as possible and within 14 hours of admission, and continue for the duration of the hospital stay or 7 days, whichever is longer.[631]

  • Low molecular weight heparin, unfractionated heparin, or fondaparinux are the recommended options for standard thromboprophylaxis.[2] The National Institute for Health and Care Excellence in the UK recommends low molecular weight heparin first-line, with fondaparinux or unfractionated heparin reserved for patients who cannot have low molecular weight heparin.[631] 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.[633][634]

  • The optimal dose is unknown. Standard prophylaxis doses are recommended over intermediate- or full treatment-dose regimens in patients without an established indication for higher-dose anticoagulation.[2][631][633] 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.[635] 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.[632][636] The National Institute for Health and Care Excellence in the UK only recommends considering intermediate doses in patients who are having advanced respiratory support, and the decision should be based on multidisciplinary or senior opinion, or locally agreed protocols.[631] Reassess VTE and bleeding risks daily in these patients.[631] NHS England recommends that therapeutic doses should not be offered unless there is a standard indication for therapeutic anticoagulation, as trials show that therapeutic doses do not improve clinical outcome of severe disease in the critical care setting.[637] Dose adjustments may be required in patients with extremes of body weight or renal impairment.[631]

  • For patients who are already on an anticoagulant for another condition, continue the patient’s current therapeutic dose unless contraindicated by a change in clinical circumstances. Consider switching to low molecular weight heparin if the patient’s clinical condition is deteriorating and the patient is not currently on low molecular weight heparin.[631]

  • Monitor patients for signs and symptoms suggestive of thromboembolism and proceed with appropriate diagnostic and management pathways if clinically suspected.[2] If the patient’s clinical condition changes, assess the risk of VTE, reassess the bleeding risk, and review VTE prophylaxis.[631]

  • Continue until hospital discharge.[2] Routine post-discharge VTE prophylaxis is not generally recommended, except in certain high-risk patients.[3][632][633] Ensure patients who require VTE prophylaxis after discharge are able to use it correctly or have arrangements made for someone to help them.[631]

  • There is currently insufficient evidence to determine the risks and benefits of prophylactic anticoagulation in hospitalised patients with COVID-19.[638] 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.[639] An observational cohort study of over 4000 patients found that early initiation of prophylactic anticoagulation in hospitalised patients was associated with a decreased risk of 30-day mortality and no increased risk of serious bleeding events compared with no anticoagulation.[640] Clinicians should rely on pre-COVID-19 evidence-based principles of anticoagulation management combined with rational approaches to address clinical challenges.[632]

Antimicrobials

  • 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][561]

  • 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.[562] 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.[561] 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.[561]

  • 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] A meta-analysis found that the prevalence of antibiotic prescribing in patients with COVID-19 was 75%, which is significantly higher than the estimated prevalence of bacterial co-infection. Therefore, unnecessary antibiotic use is likely to be high in these patients.[641]

  • Treat laboratory-confirmed co-infections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[2] The treatment of influenza is the same in all patients regardless of SARS-CoV-2 co-infection. Start empirical treatment with oseltamivir in hospitalised patients who are suspected of having either or both infections as soon as possible without waiting for influenza test results. Antiviral therapy can be stopped once influenza has been ruled out.[3]

Corticosteroids

  • The WHO strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with severe or critical disease. 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 disease. They also probably reduce the need for invasive ventilation. There is no evidence directly comparing dexamethasone and hydrocortisone. The harms of treatment in this context are considered to be minor. It is unclear whether these recommendations can be applied to children or those who are immunocompromised. The WHO does not recommend corticosteroids in patients with non-severe disease as they may increase the risk of mortality in these patients.[595][642][643] There is also evidence that corticosteroids probably reduce the length of intensive care unit stay (low certainty), and increase ventilator-free days (moderate certainty).[644][645]

  • In the UK, the National Institute for Health and Care Excellence recommends dexamethasone or hydrocortisone in patients with severe or critical COVID-19 (in line with WHO guidance). The marketing authorisations cover this indication in the UK.[593] 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.[646]

  • In the US, the National Institutes of Health guidelines panel recommends dexamethasone, either alone or in combination with remdesivir (see the Emerging external link opens in a new windowsection for information on remdesivir), in hospitalised patients who require supplemental oxygen. 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.[3] The Infectious Diseases Society of America supports the use of dexamethasone in hospitalised patients with severe disease.[647]

  • 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.[593]

  • Inhaled corticosteroids (e.g., budesonide) are also undergoing clinical trials.[648]

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

Monitor

  • Monitor patients closely for signs of clinical deterioration, and respond immediately with appropriate supportive care interventions.[2]

Discharge and rehabilitation

  • 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]

Palliative care

  • Palliative care interventions should be made accessible at each institution that provides care for patients with COVID-19. Identify whether the patient has an advance care plan and respect the patient’s priorities and preferences when formulating the patient’s care plan.[2] Follow local palliative care guidelines.

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. Use existing care bundles (i.e., three or more evidence-informed practices delivered together and consistently to improve care), chosen locally by the hospital or intensive care unit and adapted as necessary for local circumstances.[2]

Location of care

  • Manage patients in an intensive/critical care unit under the guidance of a specialist team.[2]

  • 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.[594]

Isolation period

  • 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 CDC recommends discontinuing isolation once at least 10 days and up to 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. Consider consultation with infection control experts before discontinuing isolation. Severely immunocompromised patients may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts before discontinuing isolation. Alternatively, the CDC recommends at least two negative 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; however, a test-based strategy can be considered in severely immunocompromised patients.[616]

  • 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. Immunocompetent patients who tested positive on RT-PCR and have completed their 14-day isolation period are exempt from testing prior to hospital discharge if they are within 90 days from their initial illness onset or test, unless they develop new symptoms.[606]

Infection prevention and control

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

High-flow nasal oxygen or non-invasive ventilation

  • 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 (ARDS). Consider awake prone positioning (for 8-12 hours/day, broken into shorter periods over the day) in severely ill patients who require HFNO or non-invasive ventilation.[2]

  • Airborne precautions are recommended for these interventions (including bubble CPAP) due to uncertainty about the potential for aerosolisation.[2] Novel methods to protect clinicians without access to standard personal protective equipment during aerosol-generating procedures have been suggested.[649][650][651][652]

  • Patients with hypercapnia, haemodynamic instability, multi-organ failure, or abnormal mental status should generally not receive HFNO, although emerging data suggests 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.[653] 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.[654] Other guidelines recommend HFNO over non-invasive ventilation, unless HFNO is not available.[3][621] Despite the trend to avoid HFNO, it has been shown to have a similar risk of aerosol generation to standard oxygen masks.[655]

  • 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).[654]

  • Indirect and low-certainty evidence suggests that non-invasive ventilation probably reduces mortality in patients with COVID-19, similar to mechanical ventilation, but may increase the risk of viral transmission.[656][657]

  • Monitor patients closely for acute deterioration. If patients do not improve after a short trial of these interventions, they require urgent endotracheal intubation.[2][621]

  • More detailed guidance on the management of ARDS in COVID-19 is beyond the scope of this topic; consult a specialist for further guidance.

Mechanical ventilation

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

  • Two-thirds of patients who required critical care in the UK had mechanical ventilation within 24 hours of admission.[658] In New York, 33% of hospitalised patients developed respiratory failure leading to mechanical ventilation. These patients were more likely to be male, have obesity, and have elevated inflammatory markers and liver function tests.[421] Patients spent an average of 18 days on a ventilator (range 9-28 days).[659] Patients who required invasive mechanical ventilation had an 36% to 88% mortality rate in studies.[660][661][662]

  • 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% FiO₂ for 5 minutes.[2]

  • Mechanically ventilated patients with ARDS should receive a lung-protective, low tidal volume/low inspiratory pressure ventilation strategy (lower targets are recommended in children). A higher positive end-expiratory pressure (PEEP) strategy is 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][621] NHS England recommends a low PEEP strategy in patients with normal compliance where recruitment may not be required.[663]

  • 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.[664][665][666][667][668][669] However, this approach has been criticised.[670][671] 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.[672] 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.[664] PEEP should always be carefully titrated.[673]

  • 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][621] Longer durations may be feasible in some patients.[674] A small cohort study of 12 patients in Wuhan City, China, with COVID-19-related ARDS suggests that spending periods of time in the prone position may improve lung recruitability.[675] Two small case series found that many people tolerate the prone position while awake, breathing spontaneously, or receiving non-invasive ventilation. In the patients who tolerated it, improvement in oxygenation and a decrease in respiratory rate occurred.[676][677]

  • Lung recruitment manoeuvres are suggested, but staircase recruitment manoeuvres are not recommended.[3][621]

  • More detailed guidance on the management of ARDS in COVID-19, including sedation and the use of neuromuscular blockade during ventilation, is beyond the scope of this topic; consult a specialist for further guidance.

Inhaled pulmonary vasodilator

  • Consider a trial of an inhaled pulmonary vasodilator in adults who have severe ARDS and hypoxaemia despite optimising ventilation. Taper off if there is no rapid improvement in oxygenation.[3][621]

Extracorporeal membrane oxygenation

  • Consider extracorporeal membrane oxygenation (ECMO) according to availability and expertise if the above methods fail.[2][621][678][679] ECMO is not suitable for all patients, and only those who meet certain inclusion criteria may be considered for ECMO.[680]

  • There is insufficient evidence to recommend either for or against the routine use of ECMO.[3]

  • 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.[681] An international cohort study of 1035 patients found that both the estimated mortality 90 days after ECMO initiation and mortality in those who achieved a final outcome of death or discharge were <40%, consistent with previously reported survival rates in acute hypoxaemic respiratory failure.[682]

  • Single-access, dual-stage venovenous ECMO with early extubation appears to be safe and effective in patients with COVID-19 respiratory failure.[683]

Management of septic shock/sepsis

Symptom management and supportive care

  • Consider fluid and electrolyte management, antimicrobial treatment, VTE prophylaxis, and symptom management as appropriate (see above).

  • Unfractionated heparin is preferred over fondaparinux in critically ill patients if low molecular weight heparin cannot be used.[633] Some guidelines recommend that escalated doses can be considered in critically ill patients.[632][636] The National Institute for Health and Care Excellence in the UK only recommends considering intermediate doses in patients who are having advanced respiratory support, and the decision should be based on multidisciplinary or senior opinion, or locally agreed protocols. Reassess VTE and bleeding risks daily in these patients.[631] NHS England recommends that therapeutic doses should not be offered unless there is a standard indication for therapeutic anticoagulation, as trials show that therapeutic doses do not improve clinical outcome of severe disease in the critical care setting.[637]

Corticosteroids

  • Consider systemic corticosteroids for the management of critically ill patients (see above). In the US, the National Institutes of Health guidelines panel recommends dexamethasone, either alone or in combination with remdesivir, in hospitalised patients who require high-flow oxygen or non-invasive ventilation. The panel recommends dexamethasone alone in patients on mechanical ventilation or ECMO.[3]

  • A meta-analysis found an increased risk of VTE with corticosteroid administration in patients with critical disease. However, no definite findings were available due to the differing corticosteroid regimens and the heterogeneity of the studies.[684]

Discharge and rehabilitation

  • 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]

Palliative care

  • Palliative care interventions should be made accessible at each institution that provides care for patients with COVID-19. Identify whether the patient has an advance care plan and respect the patient’s priorities and preferences when formulating the patient’s care plan.[2] Follow local palliative care guidelines.

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] In women with severe or critical disease, the multidisciplinary team should be organised as soon as possible after maternal hypoxaemia occurs in order to assess fetal maturity, disease progression, and the best options for delivery.[685]

There are limited data available on the management of pregnant women with COVID-19; however, pregnant women can generally be treated with the same supportive therapies detailed above, taking into account the physiological changes that occur with pregnancy.[2]

The prevalence of asymptomatic SARS-CoV-2-positive pregnant women admitted for delivery appears to be low (<3% in a cohort in Connecticut, and 0.43% in a cohort in California).[686][687] Screening women and their delivery partners before admission may not be helpful. More than 15% of asymptomatic maternity patients tested positive for SARS-CoV-2 infection despite having been screened negative using a telephone screening tool in one small observational study in New York. In addition to this, 58% of their asymptomatic support persons tested positive despite being screened negative.[688] Another study in a New York obstetric population found that 88% of women who tested positive for SARS-CoV-2 at admission were asymptomatic at presentation.[689]

Location of care

  • Manage pregnant women in a healthcare facility, in a community facility, or at home. 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] Follow local infection prevention and control procedures as for non-pregnant people.

  • Consider home care in women with asymptomatic or mild illness, provided the patient has no signs of potentially severe illness (e.g., breathlessness, haemoptysis, new chest pain/pressure, anorexia, dehydration, confusion), no comorbidities, and no obstetric issues; the patient is able to care for herself; and monitoring and follow-up is possible. Otherwise, manage pregnant women in a hospital setting with appropriate maternal and fetal monitoring whenever possible.[491][690][691]

  • Postpone routine antenatal or postnatal health visits for women who are in home isolation and reschedule them after the isolation period is completed. Delivery of counselling and care should be conducted via telemedicine whenever possible. Counsel women about healthy diet, mobility and exercise, intake of micronutrients, smoking, and alcohol and substance use. Advise women to seek urgent care if they develop any worsening of illness or danger signs, or danger signs of pregnancy.[2]

  • The American College of Obstetricians and Gynecologists has published an algorithm to help decide whether hospital admission or home care is more appropriate. ACOG: outpatient assessment and management for pregnant women with suspected or confirmed novel coronavirus (COVID-19) external link opens in a new window

Antenatal corticosteroids

  • Consider antenatal corticosteroids for fetal lung maturation in women who are at risk of preterm birth (24 to 37 weeks’ gestation). Caution is advised because corticosteroids could potentially worsen the maternal clinical condition, and the decision should be made in conjunction with the multidisciplinary team.[491][691][692] The WHO recommends antenatal corticosteroids only when there is no clinical evidence of maternal infection and adequate childbirth and newborn care is available, and in women with mild COVID-19 after assessing the risks and benefits.[2]

  • There is no evidence that corticosteroids in the doses prescribed for fetal lung maturation cause any harm in the context of COVID-19, but there is also no evidence of safety. The unknown effect on maternal outcome should be weighed against the neonatal benefit, particularly at later preterm gestations.[693]

Treatments

  • Most clinical trials to date have excluded pregnant women. However, potentially effective treatments should not be withheld from pregnant women due to theoretical concerns about the safety of these therapeutic agents in pregnancy. Decisions should be made with a shared decision-making process between the patient and the clinical team.[3]

  • There is no convincing evidence that systemic corticosteroids increase the incidence of congenital abnormalities. The benefits of corticosteroids in pregnant or breastfeeding women with severe or critical disease are thought to outweigh the risks.[593]

VTE prophylaxis

  • The National Institutes of Health recommends prophylactic dose anticoagulation in pregnant women who are hospitalised with severe disease, provided there are no contraindications to its use. Anticoagulation during labour and delivery requires specialised care and planning, and should be managed in a similar way to pregnant women with other conditions that require anticoagulation. VTE prophylaxis after discharge is not recommended.[3]

  • The Royal College of Obstetricians and Gynaecologists (RCOG) has also published guidance on the prevention of VTE in pregnant women.[693]

Labour and delivery

  • Implement local infection prevention and control measures during labour and delivery. Screen birth partners for COVID-19 infection using the standard case definition.[2]

  • Individualise mode of birth based on obstetric indications and the woman’s preferences. Vaginal delivery is preferred in women with confirmed infection to avoid unnecessary surgical complications. Induction of labour, interventions to accelerate labour and delivery, and caesarean delivery are generally only recommended when medically justified based on maternal and fetal condition. COVID-19 positive status alone is not an indication for caesarean section.[2][491][691] Avoid using birthing pools in patients with suspected or confirmed infection.[693]

  • Delayed umbilical cord clamping (not earlier than 1 minute after birth) is recommended for improved maternal and infant health and nutrition outcomes. The risk of transmission via blood is thought to be minimal, and there is no evidence that delayed cord clamping increases the risk of viral transmission from the mother to the newborn.[2]

  • Consider babies born to mothers with suspected or confirmed infection to be a person under investigation and isolate them from healthy newborns. Test them for infection 24 hours after birth, and, if negative, again 48 hours after birth.[694]

Newborn care

  • Experts are divided on separating mother and baby after delivery; make decisions on a case-by-base basis using shared-decision making.

  • A retrospective cohort analysis, the largest series to date, found no clinical evidence of vertical transmission in 101 newborns born to mothers with suspected or confirmed SARS-CoV-2 infection, despite most newborns rooming-in and direct breastfeeding practices. This suggests that separation may not be warranted and breastfeeding appears to be safe.[695] Mother-to-infant transmission appears to be rare during rooming-in, provided that adequate droplet and contact precautions are taken.[696]

  • The WHO recommends that mothers and infants should remain together unless the mother is too sick to care for her baby. Breastfeeding should be encouraged while applying appropriate infection prevention and control measures (e.g., performing hand hygiene before and after contact with the baby, wearing a mask while breastfeeding).[2] The WHO advises that the benefits of breastfeeding outweigh the potential risks for transmission.[697]

  • The CDC recommends that temporary separation of a newborn from a mother with confirmed or suspected COVID-19 may be considered after weighing the risks and benefits as current evidence suggests the risk of a neonate acquiring infection from its mother is low; healthcare providers should respect maternal autonomy in the medical decision-making process. If separation is not undertaken, measures to minimise the risk of transmission should be implemented.[698] A mother with confirmed infection should be counselled to take all possible precautions to avoid transmission to the infant during breastfeeding (e.g., hand hygiene, wearing a cloth face covering). Expressed milk should be fed to the newborn by a healthy carer.[699]

  • The RCOG recommends that mothers with confirmed infection and healthy babies are kept together in the immediate postnatal period. It is recommended that the risks and benefits are discussed with neonatologists and families in order to individualise care in babies who may be more susceptible to infection. The RCOG advises that the benefits of breastfeeding outweigh any potential risks of transmission of the virus through breast milk, and recommends appropriate preventive precautions to limit transmission to the baby.[693]

  • The American Academy of Pediatrics (AAP) recommends that temporary separation is the safest option, but acknowledges there are situations where this is not possible or the mother chooses to room-in. The AAP supports breastfeeding as the best choice for feeding. Breast milk can be expressed after appropriate hygiene measures and fed by an uninfected carer. If the mother chooses to breastfeed the infant themselves, appropriate prevention measures are recommended. After discharge, advise mothers with COVID-19 to practice prevention measures (e.g., distance, hand hygiene, respiratory hygiene/mask) for newborn care until either: they are afebrile for 72 hours without use of antipyretics and at least 10 days have passed since symptoms first appeared; or they have at least two consecutive negative SARS-CoV-2 tests from specimens collected ≥24 hours apart. This may require the support of an uninfected carer. A newborn with documented infection requires close outpatient follow-up after discharge for 14 days after birth.[694]

Recommendations for the triage, management, and treatment of COVID-19 in people with HIV are the same as those for the general population. Continue antiretroviral therapy and prophylaxis for opportunistic infections whenever possible, including patients who require hospitalisation. Consult with a HIV specialist before adjusting or switching antiretroviral medications, and pay attention to potential drug-drug interactions and overlapping toxicities with COVID-19 treatments.[3]

Best Practice has published a separate topic on the management of co-existing conditions in the context of COVID-19. BMJ Best Practice: management of co-existing conditions in the context of COVID-19 external link opens in a new window

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