Approach

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

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

Key recommendations

  • 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][528] 

  • Provide symptom relief as necessary. This may include treatments for fever, cough, breathlessness, anxiety, delirium, or agitation.[2][529]

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

  • Consider empiric 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][488] 

  • 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][528][530]

  • Consider remdesivir in select hospitalized patients. Remdesivir may reduce mortality and time to symptom resolution compared with standard of care.[3][531][532][533]

  • 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] 

  • For full details and guidance see information below.

Location of care

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.

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 ages 75 years and over), heart failure, male sex, chronic kidney disease, and increased body mass index (BMI).[534] The median time from onset of symptoms to hospital admission is around 7 days.[33][452]

Approximately 8.6% of patients with COVID-19 who were discharged from an emergency department returned within 72 hours. Nearly 5% of patients were admitted to hospital within 72 hours of the initial visit, and 8.2% were admitted within 7 days. Risk factors associated with an increased rate of return admission included older age, abnormal chest x-ray, fever, and hypoxia on presentation.[535]

Children are less likely to require hospitalization, but if admitted, generally only require supportive care.[17][195] Risk factors for intensive care admission in children include age <1 month, male sex, preexisting medical conditions, and presence of lower respiratory tract infection signs or symptoms at presentation.[536] The majority of children who require ventilation have underlying comorbidities, most commonly cardiac disease.[385] Children with COVID-19 are reported to have similar hospitalization rates, intensive care admission rates, and mechanical ventilator use compared with those with seasonal influenza.[501]

Overall, 19% of hospitalized patients require noninvasive ventilation, 17% require intensive care, 9% require invasive ventilation, and 2% require extracorporeal membrane oxygenation.[453] 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%.[537] The most common reasons for intensive care unit admission are hypoxemic respiratory failure leading to mechanical ventilation and hypotension.[538] 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).[539] 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.[534]

Management of mild COVID-19

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 judgment 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 caregiver is able to provide care and recognize when the patient may be deteriorating; the caregiver has adequate support (e.g., food, supplies, psychological support); the support of a trained health worker is available in the community.[508] 

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 Centers for Disease Control and Prevention (CDC) recommends discontinuing home isolation once at least 10 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing home isolation once at least 10 days have passed since the date of a positive test. Alternatively, it recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used.[540] If the patient is hospitalized, 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.[541]

Infection prevention and control

Symptom management

  • Fever and pain: acetaminophen or ibuprofen are recommended.[2][529] There is no evidence at present of severe adverse events in COVID-19 patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or of effects as a result of the use of NSAIDs on acute healthcare utilization, long-term survival, or quality of life in patients with COVID-19.[2][529][542][543][544][545][546][547] 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 ages 1 year and older) to help cough.[529] 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.[548]

  • 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.[549]

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).[2][529] 

  • 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]

Management of moderate COVID-19

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 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 home isolation once at least 10 days (not severely immunocompromised) or 20 days (severely immunocompromised) have passed since the date of a positive test. Alternatively, it recommends at least two negative RT-PCR tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred in these patients.[550] 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 hospitalized patients, and 10 days in patients with milder disease who are managed in the community.[541]

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 empiric 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 empiric 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). There is no evidence to support the use of pulse oximeters in the home setting.[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]

Remdesivir

  • Consider remdesivir, a broad-spectrum investigational antiviral agent, in hospitalized patients with moderate disease.[533] The American College of Physicians bases this recommendation on low-certainty evidence that suggests remdesivir may slightly reduce mortality and serious adverse events, reduce time to clinical improvement and recovery, and reduce the need for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) in hospitalized patients with moderate disease, compared with standard of care.[551]

  • In the US, the National Institutes of Health guidelines panel does not recommend either for or against remdesivir for the treatment of patients with moderate or mild disease as there are insufficient data. However, the panel recognizes that there may be situations in which a clinician judges that remdesivir is an appropriate treatment for a hospitalized patient with moderate disease (e.g., a person who is at a particularly high risk for clinical deterioration).[3] The Infectious Diseases Society of America does not routinely recommend remdesivir in patients with moderate disease due to a lack of evidence.[532]

  • The Food and Drug Administration has approved remdesivir for the treatment of COVID-19 in hospitalized children (≥12 years of age and ≥40 kg) and adults. The approval does not cover the entire population that had previously been authorized under the original emergency-use authorization. The emergency-use authorization has now been revised to authorize use of remdesivir in hospitalized children who weigh between 3.5 kg and 40 kg, and children <12 years of age who weigh at least 3.5 kg.[552] In the UK and Europe, remdesivir is only conditionally approved in adolescents ≥12 years of age and adults with pneumonia who require supplemental oxygen (usually classified as severe disease).[553]

  • Remdesivir may reduce mortality and time to symptom resolution in hospitalized patients compared with standard of care or placebo; however, there is no convincing evidence that remdesivir reduces the need for mechanical ventilation. The benefit of remdesivir was larger when given earlier in the illness.[531][554] However, interim results from the WHO Solidarity trial found that remdesivir appears to have little or no effect on 28-day mortality or the in-hospital course among hospitalized patients.[555]

  • The European Medicines Agency has started a review of a safety signal to assess reports of acute kidney injury in some patients. At this stage, it has not been determined whether there is a causal relationship between remdesivir and acute kidney injury.[556]

Management of severe COVID-19

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 large observational study found that disease outcomes were better predicted by frailty than either age or comorbidity; frailty (CFS score 5-8) was associated with earlier death and longer duration of hospital stay, and these outcomes worsened with increasing frailty after adjustment for age and comorbidity.[557]

  • 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.[528]

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 20 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing isolation once at least 20 days have passed since the date of a positive test. Alternatively, it recommends at least two negative RT-PCR tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred in these patients.[550]

  • 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 hospitalized patients.[541]

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 hypoxemia.[558] 

  • 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 nonpregnant 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%.[559] 

  • Some centers may recommend different SpO₂ targets in order to support prioritization of oxygen flow for the most severely ill patients in hospital. NHS England recommends a target of 92% to 95% (or 90% to 94% if clinically appropriate), for example.[560] 

  • Consider positioning techniques (e.g., high supported sitting, prone position), and airway clearance management to assist with secretion clearance in adults.[2] Oxygen delivery can be increased by using a nonrebreathing mask and prone positioning.[561] Consider a trial of awake prone positioning to improve oxygenation in patients with persistent hypoxemia despite increasing supplemental oxygen requirements in whom endotracheal intubation is not otherwise indicated.[3] Early self-proning of awake, nonintubated patients has been shown to improve oxygen saturation and may delay or reduce the need for intensive care.[562][563][564][565][566] 

  • Monitor patients closely for signs of progressive acute hypoxemic 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 hyperglycemia or metabolic acidosis, according to local protocols.[567] 

  • Fever and pain: acetaminophen or ibuprofen are recommended.[2][529] There is no evidence at present of severe adverse events in COVID-19 patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, or of effects as a result of the use of NSAIDs on acute healthcare utilization, long-term survival, or quality of life in patients with COVID-19.[542][543][544][545][546][547] 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 ages 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.[529] 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.[548]

  • 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 edema). 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.[529] 

  • Anxiety, delirium, and agitation: identify and treat any underlying or reversible causes (e.g., offer reassurance, treat hypoxia, correct metabolic or endocrine abnormalities, address coinfections, minimize use of drugs that may cause or worsen delirium, treat substance withdrawal, maintain normal sleep cycles, treat pain or breathlessness).[2][529] 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.[529] Low doses of haloperidol (or another suitable antipsychotic) can also be considered for agitation.[2] Nonpharmacologic interventions are the mainstay for the management of delirium when possible, and prevention is key.[568]

  • Mouth care: an important part of overall patient care in hospitalized patients who are ventilated or nonventilated and those undergoing step-down or end-of-life care.[569]

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

Venous thromboembolism prophylaxis

  • Start venous thromboembolism (VTE) prophylaxis in acutely ill hospitalized adults and adolescents with COVID-19 as per the standard of care for other hospitalized patients without COVID-19, provided there are no contraindications. A COVID-19 diagnosis should not influence a pediatrician’s recommendations about VTE prophylaxis in hospitalized children. Pregnant women should be managed by a specialist.[2][3][570][571]

  • Low molecular weight heparin or fondaparinux are preferred over unfractionated heparin in order to reduce patient contact. Unfractionated heparin is contraindicated in patients with severe thrombocytopenia. Fondaparinux is recommended in patients with a history of heparin-induced thrombocytopenia. Direct oral anticoagulants are not recommended. Mechanical thromboprophylaxis (e.g., intermittent pneumatic compression devices) is recommended if anticoagulation is contraindicated or not available.[2][571][572] 

  • The optimal dose is unknown. Standard prophylaxis doses are recommended over intermediate- or full treatment-dose regimens.[571] 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.[573] 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.[570] 

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

  • Routine post-discharge VTE prophylaxis is not generally recommended, except in certain high-risk patients.[3][570][571] 

  • A retrospective analysis of over 4000 patients found that anticoagulation was associated with lower mortality and intubation among hospitalized COVID-19 patients. Therapeutic anticoagulation was associated with lower mortality compared with prophylactic anticoagulation, but the difference was not statistically significant.[574] However, there is little high-quality evidence for VTE prophylaxis in COVID-19 patients; therefore, clinicians should rely on pre-COVID-19 evidence-based principles of anticoagulation management combined with rational approaches to address clinical challenges.[570]

Antimicrobials

  • Consider empiric 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][488] 

  • Some guidelines recommend empiric 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 empiric antimicrobial recommendations should be the same.[489] However, the National Institute for Health and Care Excellence in the UK recommends that it is reasonable not to start empiric antimicrobials if you are confident that the clinical features are typical for COVID-19.[488] There is insufficient evidence to recommend empiric 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 microbiologic 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.[488] 

  • Reassess antibiotic use daily. De-escalate empiric therapy on the basis of microbiology results and clinical judgment. 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 programs should be in place.[2] 

  • Treat laboratory-confirmed coinfections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[2]

Corticosteroids

  • The World Health Organization (WHO) strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with severe or critical disease. This recommendation is based on two meta-analyses that pooled data from eight randomized 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 milder disease as they may increase the risk of mortality in these patients.[530][531][575][576]

  • 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 authorizations cover this indication in the UK.[528] 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.[577]

  • In the US, the National Institutes of Health guidelines panel recommends dexamethasone, either alone or in combination with remdesivir, in hospitalized 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 hospitalized patients with severe disease.[532]

  • Monitor patients for adverse effects (e.g., hyperglycemia, 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.[528]

Remdesivir

  • Consider remdesivir in patients with pneumonia who require supplemental oxygen.[3][532] Remdesivir is conditionally approved in the UK and Europe for this indication in adolescents ≥12 years of age and adults.[553] The Food and Drug Administration has approved remdesivir for the treatment of COVID-19 in hospitalized children (≥12 years of age and ≥40 kg) and adults. The approval does not cover the entire population that had previously been authorized under the original emergency-use authorization. The emergency-use authorization has now been revised to authorize use of remdesivir in hospitalized children who weigh between 3.5 kg and 40 kg, and children <12 years of age who weigh at least 3.5 kg.[552] 

  • In the US, the National Institutes of Health guidelines panel recommends remdesivir, either alone or in combination with dexamethasone, in hospitalized patients who require supplemental oxygen. If a patient progresses to requiring high-flow oxygen, ventilation, or ECMO while on remdesivir, the panel recommends that the course of remdesivir be completed.[3] The Infectious Diseases Society of America recommends remdesivir in hospitalized patients with severe disease who are on oxygen, mechanical ventilation, or ECMO; however, it also recommends prioritizing treatment in patients who are on oxygen therapy only when supply is limited.[532] 

  • Remdesivir may reduce mortality and time to symptom resolution in hospitalized patients compared with standard of care or placebo; however, there is no convincing evidence that remdesivir reduces the need for mechanical ventilation. The benefit of remdesivir was larger when given earlier in the illness.[531][554] However, interim results from the WHO Solidarity trial found that remdesivir appears to have little or no effect on 28-day mortality or the in-hospital course among hospitalized patients.[555] An expert guideline panel makes a weak recommendation for the use of remdesivir in severe disease, and supports more randomized trials as the quality of the evidence is low.[578]

  • A UK National Institute for Health and Care Excellence review suggests there is some benefit with remdesivir compared with placebo for reducing supportive measures including mechanical ventilation and reducing time to recovery in patients who are on oxygen therapy. However, no statistically significant differences were found for mortality and serious adverse events.[579] 

  • The European Medicines Agency has started a review of a safety signal to assess reports of acute kidney injury in some patients. At this stage, it has not been determined whether there is a causal relationship between remdesivir and acute kidney injury.[556]

Experimental therapies

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

Evidence for COVID-19 drug treatments

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.

Management of critical COVID-19

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.[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 preexisting advanced comorbidities.[529]

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 20 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing isolation once at least 20 days have passed since the date of a positive test. Alternatively, it recommends at least two negative RT-PCR tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred in these patients.[550] 

  • 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 hospitalized patients.[541]

Infection prevention and control

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

High-flow nasal oxygen or noninvasive ventilation

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

  • Airborne precautions are recommended for these interventions (including bubble CPAP) due to uncertainty about the potential for aerosolization.[2] Novel methods to protect clinicians without access to standard personal protective equipment during aerosol-generating procedures have been suggested.[580][581][582][583]

  • Patients with hypercapnia, hemodynamic 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 nonworsening hypercapnia. Patients with hypoxemic respiratory failure and hemodynamic 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.[584] NHS England recommends CPAP as the preferred form of noninvasive ventilation in patients with hypoxemic (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.[585] Other guidelines recommend HFNO over noninvasive ventilation, unless HFNO is not available.[3][559] Despite the trend to avoid HFNO, it has been shown to have a similar risk of aerosol generation to standard oxygen masks.[586] 

  • 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).[585]

  • Indirect and low-certainty evidence suggests that noninvasive ventilation probably reduces mortality in patients with COVID-19, similar to mechanical ventilation, but may increase the risk of viral transmission.[587][588] 

  • Monitor patients closely for acute deterioration. If patients do not improve after a short trial of these interventions they require urgent endotracheal intubation.[2][559] 

  • 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/noninvasive ventilatory support measures.[2][3] 

  • Two-thirds of patients who required critical care in the UK had mechanical ventilation within 24 hours of admission.[589] In New York, 33% of hospitalized 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.[367] Patients spent an average of 18 days on a ventilator (range 9-28 days).[590] Patients who required invasive mechanical ventilation had an 36% to 88% mortality rate in studies.[591][592][593]

  • 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 preoxygenation 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, individualization 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][559] NHS England recommends a low PEEP strategy in patients with normal compliance where recruitment may not be required.[594] 

  • 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 hypoxemia.[595][596][597][598][599][600] However, this approach has been criticized.[601][602] 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.[603] 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 physiologic findings rather than using standard protocols. High PEEP may have a detrimental effect on patients with normal compliance.[595] PEEP should always be carefully titrated.[561] 

  • 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][559] Longer durations may be feasible in some patients.[604] 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.[605] Two small case series found that many people tolerate the prone position while awake, breathing spontaneously, or receiving noninvasive ventilation. In the patients who tolerated it, improvement in oxygenation and a decrease in respiratory rate occurred.[606][607] 

  • Lung recruitment maneuvers are suggested, but staircase recruitment maneuvers are not recommended.[3][559]

  • 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 hypoxemia despite optimizing ventilation. Taper off if there is no rapid improvement in oxygenation.[3][559]

Extracorporeal membrane oxygenation

  • Consider ECMO according to availability and expertise if the above methods fail.[2][559][608][609] ECMO is not suitable for all patients, and only those who meet certain inclusion criteria may be considered for ECMO.[610]

  • 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.[611] 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 hypoxemic respiratory failure.[612]

  • Single-access, dual-stage venovenous ECMO with early extubation appears to be safe and effective in patients with COVID-19 respiratory failure.[613]

Management of septic shock/sepsis

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

Symptom management and supportive care

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

  • VTE prophylaxis is recommended in critically ill patients. Low molecular weight heparin is the preferred option, with unfractionated heparin considered a suitable alternative and preferred over fondaparinux.[571]

Corticosteroids

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

Remdesivir

  • Consider remdesivir in select patients with pneumonia who require supplemental oxygen (see above). In the US, the National Institutes of Health recommends remdesivir, in combination with dexamethasone, in hospitalized patients who require high-flow oxygen, noninvasive ventilation, mechanical ventilation, or ECMO.[3]

Experimental therapies

  • Consider experimental therapies (see the Emerging section).

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.

Management of pregnant women

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-centered, respectful, skilled approach to care is recommended.[2] In women with severe or critical disease, the multidisciplinary team should be organized as soon as possible after maternal hypoxemia occurs in order to assess fetal maturity, disease progression, and the best options for delivery.[614] 

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 physiologic 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).[615][616] 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.[617] 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.[618] 

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 nonpregnant people.

  • Consider home care in women with asymptomatic or mild illness, provided the patient has no signs of potentially severe illness (e.g., breathlessness, hemoptysis, 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.[430][619][620] 

  • Postpone routine prenatal or postpartum health visits for women who are in home isolation and reschedule them after the isolation period is completed. Delivery of counseling 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

Prenatal corticosteroids

  • Consider prenatal 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.[430][620][621] The WHO recommends prenatal 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] Corticosteroids for fetal lung maturation have not been shown to cause more harm in patients with COVID-19.[622]

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.[528] 

Labor and delivery

  • Implement local infection prevention and control measures during labor and delivery. A negative pressure isolation room is recommended if available. Screen birth partners for COVID-19 infection using the standard case definition.[2]

  • Individualize 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 labor, interventions to accelerate labor and delivery, and cesarean delivery are generally only recommended when medically justified based on maternal and fetal condition. COVID-19 positive status alone is not an indication for cesarean section.[2][430][620] Avoid using birthing pools in patients with suspected or confirmed infection.[622] 

  • 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.[623] 

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.[624]

  • 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.[625]

  • 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 minimize the risk of transmission should be implemented.[626] A mother with confirmed infection should be counseled 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 caregiver.[627] 

  • The Royal College of Obstetricians and Gynaecologists (RCOG) recommends that mothers with confirmed infection and healthy babies are kept together in the immediate postpartum period. It is recommended that the risks and benefits are discussed with neonatologists and families in order to individualize 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.[622]

  • 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 caregiver. 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 caregiver. A newborn with documented infection requires close outpatient follow-up after discharge for 14 days after birth.[623]

Management of people living with HIV

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 hospitalization. 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]

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