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.[120]

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.[120][600]

Provide symptom relief as necessary. This may include treatments for fever, cough, breathlessness, anxiety, delirium, or agitation.[120][600]

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.[120]

Consider empirical antibiotics if there is clinical suspicion of a secondary 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.[120][600]

Consider systemic corticosteroid therapy for 7 to 10 days in patients 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.[568][795]

Consider an interleukin-6 inhibitor (tocilizumab or sarilumab) in patients with severe or critical disease. High-certainty evidence suggests that interleukin-6 inhibitors reduce mortality and the need for mechanical ventilation.[795][796][797]

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.[120]

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.[120]

  • 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 severe acute respiratory syndrome coronavirus 2 (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.[155]

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).[798] The median time from onset of symptoms to hospital admission is around 7 days.[34][701]

Children are less likely to require hospitalisation but, if admitted, generally only require supportive care.[18][799] 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.[800] The majority of children who require ventilation have underlying comorbidities, most commonly cardiac disease.[801] 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.[777]

Overall, 19% of hospitalised patients require non-invasive ventilation, 17% require intensive care, 9% require invasive ventilation, and 2% require extracorporeal membrane oxygenation.[702] 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%.[802] Another more recent meta-analysis found the mortality rate in patients in the intensive care unit to be 35.5%.[803] The most common reasons for intensive care unit admission are hypoxaemic respiratory failure leading to mechanical ventilation and hypotension.[804] 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).[805] 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.[798] The most common risk factors for intensive care unit mortality were invasive mechanical ventilation, acute kidney injury, and acute respiratory distress syndrome.[806]

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.[120]

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.[120][568] 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.[807]

  • There is some evidence to suggest that implementation of an early home treatment algorithm reduced the risk of hospitalisation and related treatment costs in a small cohort of patients.[808]

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).[120]

  • The US Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 10 days (not moderately to severely immunocompromised) or up to 20 days (moderately to 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 moderately to severely immunocompromised) or up to 20 days (moderately to severely immunocompromised) have passed since the date of a positive test. Moderately to 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 moderately to severely immunocompromised patients.[809] 

  • 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.[810]

Infection prevention and control

Symptom management

  • Fever and pain: paracetamol or ibuprofen are recommended.[120][600] 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.[811][812][813][814][815][816][817] 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 first (e.g., a teaspoon of honey in patients aged 1 year and older) to help cough.[600] 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.[818]

  • 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.[819]

Supportive care

  • Advise patients about adequate nutrition and appropriate rehydration. Advise patients to drink fluids regularly to avoid dehydration. Fluid intake needs can be higher than usual because of fever. However, too much fluid can worsen oxygenation.[120][600]

  • Advise patients to improve air circulation by opening a window or door.[600]

  • Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate.[120]

  • Most children with mild disease can be managed with supportive care alone and will not require any specific therapy.[568]

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).[120][568]

  • 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.[120]

Corticosteroids

  • The WHO does not recommend systemic corticosteroids in patients with non-severe disease as they may increase the risk of mortality in these patients.[795]

  • In the UK, the National Institute for Health and Care Excellence does not recommend routinely using systemic corticosteroids in people who do not need supplemental oxygen, unless there is another medical indication to do so.[600]

  • In the US, the National Institutes of Health guidelines panel recommends against the use of systemic corticosteroids in non-hospitalised patients with mild to moderate disease in the absence of another indication.[568]

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.[120]

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.[120][568]

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.[120]

  • The CDC recommends discontinuing isolation once at least 10 days (not moderately to severely immunocompromised) or up to 20 days (moderately to 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 moderately to severely immunocompromised) or up to 20 days (moderately to severely immunocompromised) have passed since the date of a positive test. Moderately to 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 moderately to severely immunocompromised patients.[809] 

  • 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.[810]

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).

  • Most children with moderate disease can be managed with supportive care alone and will not require any specific therapy.[568]

Antibiotics

  • Do not offer an antibiotic for preventing secondary bacterial pneumonia in people with COVID-19.[600]

  • Consider empirical antibiotics only if there is clinical suspicion of secondary bacterial infection. Start treatment as soon as possible, and refer to local guidelines for choice of regimen.[120][568][600]

  • 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.[120]

  • Advise patients to seek medical help without delay if their symptoms do not improve, or worsen rapidly or significantly. Reconsider whether the person has signs and symptoms of more severe disease on reassessment, and whether to refer them to hospital, other acute community support services, or palliative care services.[600]

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.[120]

  • 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.[120]

    • A systematic review and meta-analysis found that the NEWS2 score had moderate sensitivity and specificity in predicting the deterioration of patients with COVID-19. The score showed good discrimination in predicting the combined outcome of the need for intensive respiratory support, admission to the intensive care unit, or in-hospital mortality.[604]

Corticosteroids

  • The WHO does not recommend systemic corticosteroids in patients with non-severe disease as they may increase the risk of mortality in these patients.[795]

  • In the UK, the National Institute for Health and Care Excellence does not recommend routinely using systemic corticosteroids in people who do not need supplemental oxygen, unless there is another medical indication to do so.[600]

  • In the US, the National Institutes of Health guidelines panel recommends against the use of systemic corticosteroids in non-hospitalised patients with mild to moderate disease in the absence of another indication. However, the guideline panel recommends oral dexamethasone in patients who are discharged from the accident and emergency department despite new or increased need for supplemental oxygen (for the duration of supplemental oxygen and not to exceed 10 days), when hospital resources are limited, inpatient admission is not possible, and close follow-up is ensured.[568]

Patients with suspected or confirmed severe disease are at risk of rapid clinical deterioration.[120]

  • 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.[120]

  • Use the Clinical Frailty Scale (CFS) to assess baseline health and inform discussions on treatment expectations when appropriate and within an individualised assessment of frailty. Clinical Frailty Scale external link opens in a new window Do not use the CFS for younger people, or for people with stable long-term disabilities (e.g., cerebral palsy), learning disabilities, or autism. Make an individualised assessment of frailty in these people, using clinical assessment and alternative scoring methods.[600]

    • 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).[820]

    • Patients with a score between 6-9 or 4-5 had significantly increased mortality compared with those with a score of 1-3. In the context of COVID-19, a score of 1-3 may be considered a lower risk of mortality, a score of 4-5 moderate risk, and a score of 6-9 high risk.[821]

    • 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.[822]

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.[120]

  • 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. Moderately to 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 moderately to severely immunocompromised patients.[809]

  • 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.[810]

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%.[120][568] There is no evidence of benefit for oxygen therapy in patients with COVID-19 in the absence of hypoxaemia.[823]

  • 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.[120] Some guidelines recommend that SpO₂ should be maintained no higher than 96%.[824]

  • 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.[825]

  • 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.[120][568]

    • Awake prone positioning of non-intubated patients was associated with improvement in oxygen variables (PaO₂/FiO₂, PaO₂, and SpO₂), respiratory rate, and mortality, but no significant difference was noted in the rate of intubation. However, evidence is limited.[826][827]

  • 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.[120][568]

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.[120] Correct any electrolyte or metabolic abnormalities, such as hyperglycaemia or metabolic acidosis, according to local protocols.[828]

  • Fever and pain: paracetamol or ibuprofen are recommended.[120][600] 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.[811][812][813][814][815][816][817] 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 first (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.[600] 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.[818]

  • 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, pulmonary embolism, COPD, asthma).[600]

  • 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).[120][600] Low doses of haloperidol (or another suitable antipsychotic) can also be considered for agitation.[120] Non-pharmacological interventions are the mainstay for the management of delirium when possible, and prevention is key.[829]

  • 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.[830]

  • Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia or depression as appropriate.[120]

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.[600]

  • Start venous thromboembolism (VTE) prophylaxis in acutely ill hospitalised adults and adolescents, provided there are no contraindications.[120][568][831][832]

    • The National Institute for Health and Care Excellence in the UK recommends starting as soon as possible (within 14 hours of admission) in young people and adults who need low-flow oxygen and who do not have an increased bleeding risk, and continuing for a minimum of 7 days including after discharge.[600]

    • For hospitalised children, indications for VTE prophylaxis should be the same as those for children without COVID-19.[568]

  • Low molecular weight heparin, unfractionated heparin, or fondaparinux are the recommended options for standard thromboprophylaxis.[120]

    • 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.[600]

    • A retrospective observational study found that enoxaparin is associated with lower 28-day mortality, lower rates of bleeding events, lower intensive care admission rates, and shorter hospital stays compared with unfractionated heparin; however, the study had important limitations and further research is required.[833]

    • Unfractionated heparin is contraindicated in patients with severe thrombocytopenia. Fondaparinux is recommended in patients with a history of heparin-induced thrombocytopenia. Mechanical thromboprophylaxis (e.g., intermittent pneumatic compression devices) is recommended if anticoagulation is contraindicated or not available.[832][834]

    • Avoid direct oral anticoagulants in the absence of an evidence-based indication for oral anticoagulation. An open-label, multicentre, randomised controlled trial found that in-hospital therapeutic anticoagulation with rivaroxaban or enoxaparin followed by rivaroxaban until day 30 did not improve clinical outcomes and increased bleeding compared with prophylactic anticoagulation among hospitalised patients with an elevated D-dimer level.[835]

  • The optimal dose is yet to be determined. Standard prophylaxis doses are generally recommended across most guidelines over intermediate- or full treatment-dose regimens in patients without an established indication for higher-dose anticoagulation.[836] However, this recommendation varies and you should consult your local guidelines.

    • The World Health Organization recommends standard thromboprophylaxis dosing of anticoagulation rather than therapeutic or intermediate dosing in patients without an established indication for higher-dose anticoagulation.[120]

    • The National Institute for Health and Care Excellence in the UK recommends a prophylactic dose of a low molecular weight heparin for a minimum of 7 days (including after discharge) in young people and adults who need low-flow oxygen and who do not have an increased bleeding risk. A treatment dose of a low molecular weight heparin for 14 days or until discharge (whichever is sooner) may be considered in young people and adults who need low-flow oxygen and who do not have an increased bleeding risk; however, this is a conditional recommendation only. The decision should be carefully considered, and choice of the most appropriate dose regimen should be guided by bleeding risk, clinical judgement, and local protocols. For those who do not need supplemental oxygen, follow standard VTE prophylaxis guidelines.[600]

    • The National Institutes of Health guidelines panel recommends prophylactic-dose anticoagulation, and states that there are insufficient data to recommend increased anticoagulant doses for VTE prophylaxis in COVID-19 patients outside the setting of a clinical trial.[568]

    • Dose adjustments may be required in patients with extremes of body weight or renal impairment.[600]

  • Evidence to support the best dose regimen is limited.

    • A systematic review and meta-analysis of nearly 33,000 hospitalised patients found that both prophylactic- and full-treatment doses of low molecular weight heparin were associated with reduced mortality; however, the full dose was associated with a higher risk of major bleeding.[837]

    • Another systematic review and meta-analysis found that although the use of prophylactic anticoagulation at an intermediate- or full-treatment dose was associated with a reduction in the risk of venous thromboembolism compared with standard-dose prophylactic anticoagulation (in patients without an indication for therapeutic anticoagulation), it was not associated with a reduction in all-cause mortality or other adverse ischaemic events but with a significant increase in major bleeding.[838]

    • The HEP-COVID randomised clinical trial found that therapeutic-dose low molecular weight heparin reduced the composite of thromboembolism and death (absolute risk reduction 13.2%) compared with standard prophylactic- or intermediate-dose low molecular weight heparin or unfractionated heparin for thromboprophylaxis, without an increased risk of major bleeding, among hospitalised patients with very elevated D-dimer levels. The effect was not seen in patients in intensive care.[839]

  • 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.[600]

  • Monitor patients for signs and symptoms suggestive of thromboembolism and proceed with appropriate diagnostic and management pathways if clinically suspected.[120] If the patient’s clinical condition changes, assess the risk of VTE, reassess the bleeding risk, and review VTE prophylaxis.[600]

  • Continue until hospital discharge.[120] Routine post-discharge VTE prophylaxis is not generally recommended, except in certain high-risk patients.[568][831][832] Ensure patients who require VTE prophylaxis after discharge are able to use it correctly or have arrangements made for someone to help them.[600]

  • There is currently insufficient evidence to determine the risks and benefits of prophylactic anticoagulation in hospitalised patients with COVID-19.[840]

    • A systematic review and meta-analysis found that the pooled odds of mortality between anticoagulated and non-anticoagulated hospitalised patients were similar, but lower in the standard prophylactic-dose group. Prophylactic-dose anticoagulation significantly decreased the odds of in-hospital death by 17% compared with no anticoagulation. Mortality increased in the intermediate- to therapeutic-dose group with an increased risk of major bleeding.[841]

    • Clinicians should rely on pre-COVID-19 evidence-based principles of anticoagulation management combined with rational approaches to address clinical challenges.[831]

Antimicrobials

  • Do not offer antibiotics for preventing or treating pneumonia if SARS-CoV-2, another virus, or a fungal infection is likely to be the cause.[600] There is insufficient evidence to recommend empiric broad-spectrum antibiotics in the absence of another indication.

  • Consider empirical antibiotics if there is clinical suspicion of secondary bacterial infection. Give within 1 hour of initial assessment for patients with suspected sepsis or if the patient meets high-risk criteria (or within 4 hours of establishing a diagnosis of secondary bacterial pneumonia); do not wait for microbiology results. Base the regimen on the clinical diagnosis (e.g., community-acquired pneumonia, hospital-acquired pneumonia, sepsis), local epidemiology and susceptibility data, and local treatment guidelines.[120][568][600]

  • Consider seeking specialist advice for people who: are immunocompromised; have a history of infection with resistant organisms; have a history of repeated infective exacerbations of lung disease; are pregnant; or are receiving advanced respiratory or organ support. Seek specialist advice if there is a suspicion that the person has an infection with multidrug-resistant bacteria and may need a different antibiotic, or there is clinical or microbiological evidence of infection and the person's condition does not improve as expected after 48 to 72 hours of antibiotic treatment.[600]

  • 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.[120] 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.[842]

  • Treat laboratory-confirmed co-infections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[120] 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.[568]

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 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 disease. There is no evidence directly comparing dexamethasone and hydrocortisone. The harms of treatment in this context are considered to be minor. It is unclear whether these recommendations can be applied to children or those who are immunocompromised.[795][796][797][843][844]

  • In the UK, the National Institute for Health and Care Excellence recommends offering dexamethasone (or an alternative such as hydrocortisone or prednisolone when dexamethasone cannot be used or is unavailable) to people who need supplemental oxygen to meet their prescribed oxygen saturation levels, or who have a level of hypoxia that needs supplemental oxygen but who are unable to have or tolerate it. Treatment is for up to 10 days unless there is a clear indication to stop early.[600]

  • 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 adults who require supplemental oxygen. Alternative corticosteroids may be used in situations where dexamethasone is not available. It is not routinely recommended for paediatric patients who require only low levels of oxygen support (i.e., via a nasal cannula only). Use of dexamethasone for the treatment of severe disease in children who are profoundly immunocompromised has not been evaluated, may be harmful, and therefore should be considered only on a case-by-case basis.[568] The Infectious Diseases Society of America supports the use of dexamethasone in hospitalised patients with severe disease.[845]

  • Monitor patients for adverse effects (e.g., hyperglycaemia, secondary infections, psychiatric effects, reactivation of latent infections) and assess for drug-drug interactions.[568]

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].

Interleukin-6 (IL-6) inhibitors

  • The WHO strongly recommends an IL-6 inhibitor (tocilizumab or sarilumab), in combination with a systemic corticosteroid and initiated at the same time, in patients with severe disease. IL-6 inhibitors are typically administered as a single intravenous dose; however, a second dose may be administered 12 to 48 hours after the first dose if the clinical response is inadequate. This recommendation is based on high-certainty evidence that shows IL-6 inhibitors reduce mortality and the need for mechanical ventilation, and low-certainty evidence that suggests that IL-6 inhibitors may also reduce the duration of mechanical ventilation and hospitalisation. The evidence regarding the risk of severe adverse events is uncertain. The applicability of this recommendation to children is currently uncertain.[795][796][797] This recommendation is based on data from the UK RECOVERY and REMAP-CAP trials.[846][847]

  • In the UK, the National Institute for Health and Care Excellence recommends a single dose of tocilizumab in hospitalised adults if all of the following conditions apply: they are having or have completed a course of corticosteroids such as dexamethasone (unless they cannot have corticosteroids); they have not had another IL-6 inhibitor during this admission; there is no evidence of a bacterial or viral infection (other than SARS-CoV-2) that might be worsened by tocilizumab; AND they either need supplemental oxygen and have a C-reactive protein level of ≥75 mg/L, OR they are within 48 hours of starting high-flow nasal oxygen, continuous positive airway pressure, non-invasive ventilation, or invasive mechanical ventilation. Consider tocilizumab for children and young people who have severe disease or paediatric inflammatory multisystem syndrome only if they are aged 1 year and over, and only in the context of a clinical trial. Sarilumab may be considered an alternative option in adults only if tocilizumab cannot be used or is unavailable (use the same eligibility criteria as those for tocilizumab).[600] Tocilizumab has not been granted a conditional marketing authorisation for this indication in the UK as yet.

  • In the US, the Infectious Diseases Society of America recommends considering tocilizumab in hospitalised adults with progressive severe disease who have elevated markers of systemic inflammation, in addition to standard of care (i.e., corticosteroids), rather than standard of care alone. Sarilumab may be used if tocilizumab is not available.[845] Tocilizumab has been granted an emergency-use authorisation in the US for the treatment of hospitalised adults and paediatric patients 2 years of age and older who are receiving systemic corticosteroids and require supplemental oxygen.[848]

  • Evidence supports the use of these drugs.

    • A Cochrane review found that tocilizumab reduced all-cause mortality at day 28, and probably resulted in slightly fewer serious adverse events compared with standard care alone or placebo. The evidence suggests uncertainty around the effect on mortality after day 60. However, tocilizumab probably results in little or no increase in clinical improvement at day 28 (i.e., hospital discharge or improvement measured by triallist-defined scales). The impact of tocilizumab on other outcomes is uncertain. Evidence for an effect of sarilumab is uncertain.[849]

    • A living systematic review and network meta-analysis found that IL-6 inhibitors are likely to reduce the need for mechanical ventilation (moderate-certainty evidence) and may reduce the duration of hospitalisation (low-certainty evidence) compared with standard care.[850][851]

    • A meta-analysis of over 10,000 hospitalised patients from 27 randomised controlled trials found that IL-6 antagonists were associated with lower all-cause mortality 28 days after randomisation compared with usual care or placebo. There was no clear association between administration of IL-6 inhibitors and all-cause mortality at 90 days; however, data were limited.[852]

Recommendations and evidence for the use of IL-6 inhibitors in hospitalised patients with COVID-19[Figure caption and citation for the preceding image starts]: Recommendations and evidence for the use of IL-6 inhibitors 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.[120]

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.[120]

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.[120]

  • There is a lack of data on palliative care in patients with COVID-19. However, a rapid systematic review of pharmacological strategies used for palliative care in these patients, the first international review of its kind, found that a higher proportion of patients required continuous subcutaneous infusions for medication delivery than is typically seen in the palliative care population. Modest doses of commonly used end-of-life medications were required for symptom control. However, these findings should be interpreted with caution due to the lack of data available.[853]

  • 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.[120]

Location of care

  • Manage patients in an intensive/critical care unit under the guidance of a specialist team.[120]

  • 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.[600]

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.[120]

  • 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. Moderately to 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 moderately to severely immunocompromised patients.[809]

  • 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.[810]

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

  • The World Health Organization recommends considering 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.[120]

  • In the UK, the National Institute for Health and Care Excellence recommends CPAP in patients with hypoxaemia that is not responding to supplemental oxygen with a fraction of inspired oxygen of ≥0.4 (40%), and escalation to invasive mechanical ventilation would be an option but it is not immediately needed or it is agreed that respiratory support should not be escalated beyond CPAP. Ensure there is access to critical care providers for advice, regular review, and prompt escalation of treatment if needed, and regular assessment and management of symptoms alongside non-invasive respiratory support. Consider using HFNO for people having CPAP when they need a break from CPAP (e.g., mealtimes), need humidified oxygen, or need weaning from CPAP. Do not routinely offer HFNO as the main form of respiratory support for people with respiratory failure in whom escalation to invasive mechanical ventilation would be appropriate. Ensure that pharmacological and non-pharmacological management strategies, including body positioning, are optimised before escalating treatment to non-invasive respiratory support.[600]

  • In the US, the National Institutes of Health guidelines panel recommends HFNO over non-invasive ventilation in patients with acute hypoxaemic respiratory failure despite conventional oxygen therapy. The panel recommends a closely monitored trial of non-invasive ventilation if HFNO is not available. A trial of awake prone positioning is recommended in patients with persistent hypoxaemia despite increasing supplemental oxygen requirements in whom endotracheal intubation is not otherwise indicated.[568]

    • 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.[854][855]

    • The RECOVERY-RS trial (an open-label, multicenter, adaptive randomised controlled trial) found that CPAP reduced the need for invasive mechanical ventilation in adults admitted to hospital with acute respiratory failure. Neither CPAP nor HFNO reduced mortality when compared with conventional oxygen therapy. This preprint study has not been published as yet.[856]

    • Awake prone positioning of non-intubated patients was associated with improvement in oxygen variables (PaO₂/FiO₂, PaO₂, and SpO₂), respiratory rate, and mortality, but no significant difference was noted in the rate of intubation. However, evidence is limited.[826][827]

  • Airborne precautions are recommended for these interventions (including bubble CPAP) due to uncertainty about the potential for aerosolisation.[120] Novel methods to protect clinicians without access to standard personal protective equipment during aerosol-generating procedures have been suggested.[857][858][859][860] Despite the trend to avoid HFNO, it has been shown to have a similar risk of aerosol generation to standard oxygen masks.[861]

  • 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.[120]

  • Monitor patients closely for acute deterioration. If patients do not improve after a short trial of these interventions, they require urgent endotracheal intubation.[120][824]

  • 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.[120][568]

    • Use of mechanical ventilation in COVID-19 patients carries a high risk of mortality. Mortality is highly variable across studies, ranging between 21% and 100%. An overall in-hospital mortality risk ratio of 0.70 has been reported based on random-effect pooled estimates. However, it is important to note that outcomes appear to have improved as the pandemic has progressed.[862]

  • Endotracheal intubation should be performed by an experienced provider using airborne precautions.[120] Intubation by video laryngoscopy is recommended if possible.[568] 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.[120]

  • 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.[120][568][824] NHS England recommends a low PEEP strategy in patients with normal compliance where recruitment may not be required.[863]

    • 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.[864][865][866][867][868][869] However, this approach has been criticised.[870][871]

    • 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.[872] 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.[864]

    • PEEP should always be carefully titrated.[873]

  • 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.[120][568][824] Longer durations may be feasible in some patients.[874]

  • Lung recruitment manoeuvres are suggested, but staircase recruitment manoeuvres are not recommended.[568][824]

  • 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.[568][824]

Extracorporeal membrane oxygenation

  • Consider extracorporeal membrane oxygenation (ECMO) according to availability and expertise if the above methods fail.[120][824][875] ECMO is not suitable for all patients, and only those who meet certain inclusion criteria may be considered for ECMO.[876]

  • There is insufficient evidence to recommend either for or against the routine use of ECMO.[568]

    • A systematic review and meta-analysis found that in-hospital mortality in adults receiving ECMO was 37.1% during the first year of the pandemic, similar to those with non-COVID-19-related acute respiratory distress syndrome. Increasing age was a risk factor for death. The duration of treatment appears to be prolonged in COVID-19 patients; however, a prolonged treatment course was not a predictor of mortality.[877]

    • Single-access, dual-stage venovenous ECMO with early extubation appears to be safe and effective in patients with COVID-19 respiratory failure.[878]

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 Management of severe COVID-19 above).

  • For VTE prophylaxis, unfractionated heparin is preferred over fondaparinux in critically ill patients if low molecular weight heparin cannot be used.[832]

    • The National Institute for Health and Care Excellence in the UK recommends a prophylactic dose of a low molecular weight heparin to young people and adults who need HFNO, CPAP, non-invasive ventilation, or invasive mechanical ventilation, and who do not have an increased bleeding risk. An intermediate or treatment dose of a low molecular weight heparin is only recommended in these patients as part of a clinical trial.[600]

    • Some guidelines recommend that escalated doses can be considered in critically ill patients.[831][611]

    • A multicentre randomised controlled trial found that intermediate-dose prophylactic anticoagulation did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or 30-day mortality compared with standard-dose prophylactic anticoagulation among patients admitted to the intensive care unit. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the intensive care unit.[879]

    • An open-label, multiplatform randomised controlled trial found that an initial strategy of therapeutic-dose heparin did not result in a greater probability of survival to hospital discharge or a greater number of organ support-free days in critically ill patients compared with usual-care thromboprophylaxis.[880]

Corticosteroids

  • The WHO strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with critical disease. Moderate-quality evidence suggests that systemic corticosteroids probably reduce 28-day mortality in patients with critical disease. They also probably reduce the need for invasive ventilation.[795] There is also evidence that corticosteroids probably increase ventilator-free days (moderate certainty).[850][851]

  • In the US, the National Institutes of Health guidelines panel recommends dexamethasone (or a suitable alternative corticosteroid), 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 high-flow oxygen or non-invasive ventilation. In patients who are on mechanical ventilation or ECMO, the panel recommends dexamethasone alone or in combination with tocilizumab for patients who are within 24 hours of admission to the intensive care unit. The panel recommends using dexamethasone in hospitalised children who require high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.[568]

    • 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.[881]

  • See the corticosteroids section under Management of severe COVID-19 above for more information.

IL-6 inhibitors

  • The WHO strongly recommends an IL-6 inhibitor, in combination with a systemic corticosteroid and initiated at the same time, in patients with critical disease.[795]

  • In the US, the National Institutes of Health guidelines panel recommends adding tocilizumab to dexamethasone (or a suitable alternative corticosteroid) or dexamethasone plus remdesivir in patients who require non-invasive mechanical ventilation or high-flow nasal oxygen and have been recently hospitalised (e.g., within 3 days) with rapidly increasing oxygen needs and systemic inflammation. In patients who are on mechanical ventilation or ECMO, the panel recommends adding tocilizumab to dexamethasone for patients who are within 24 hours of admission to the intensive care unit. There is insufficient evidence for the panel to recommend either for or against the use of tocilizumab in hospitalised children. Sarilumab may be used as an alternative if tocilizumab is not available or it is not feasible to use it.[568] The Infectious Diseases Society of America recommends considering tocilizumab in hospitalised adults with critical disease who have elevated markers of systemic inflammation, in addition to standard of care (i.e., corticosteroids), rather than standard of care alone. Sarilumab may be used if tocilizumab is not available.[845] Tocilizumab has been granted an emergency-use authorisation in the US for the treatment of hospitalised adults and paediatric patients 2 years of age and older who are receiving systemic corticosteroids and require non-invasive or invasive mechanical ventilation, or ECMO.[848]

  • See the IL-6 inhibitors section under Management of severe COVID-19 above for more information.

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.[120]

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.[120]

    • There is a lack of data on palliative care in patients with COVID-19. However, a rapid systematic review of pharmacological strategies used for palliative care in these patients, the first international review of its kind, found that a higher proportion of patients required continuous subcutaneous infusions for medication delivery than is typically seen in the palliative care population. Modest doses of commonly used end-of-life medications were required for symptom control. However, these findings should be interpreted with caution due to the lack of data available.[853]

  • 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.[120] 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.[882]

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.[120]

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).[883][884] 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 people tested positive despite being screened negative.[885] 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.[886]

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.[120] 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.[666][887][888]

  • 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.[120]

  • 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.[666][888][889] 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.[120]

  • 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.[890]

Treatments

  • In general, the therapeutic management should be the same for pregnant women as for non-pregnant patients. 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.[568]

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.[568]

  • The Royal College of Obstetricians and Gynaecologists (RCOG) has also published guidance on the prevention of VTE in pregnant women.[890]

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.[120]

  • 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.[120][666][888]

  • 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.[120]

  • 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 again 48 hours after birth.[891]

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.[892] Mother-to-infant transmission appears to be rare during rooming-in, provided that adequate droplet and contact precautions are taken.[893]

  • 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).[120] The WHO advises that the benefits of breastfeeding outweigh the potential risks for transmission.[894]

  • 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.[895] 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.[896]

  • 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.[890]

  • The American Academy of Pediatrics (AAP) recommends that mothers and newborns may room-in, with appropriate infection prevention and control precautions, according to usual centre practice. However, it may be appropriate to temporarily separate the mother and newborn (or to have the newborn cared for by non-infected carers in the mother’s room) when the mother is acutely ill with COVID-19 and cannot care for the infant in a safe way. The AAP strongly 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., hand hygiene, respiratory hygiene/mask) for newborn care until: they are afebrile for 24 hours without the use of antipyretics; at least 10 days have passed since symptoms first appeared (or 10 days since a positive test in asymptomatic women); and symptoms have improved. A newborn with documented infection but no symptoms requires close outpatient follow-up after discharge for 14 days after birth.[891]

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.[568]

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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