Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
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.[139]
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.[139][501] 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.[700] The location of care will depend on guidance from local health authorities and available resources.
Pregnant women with suspected or confirmed mild disease may not require acute care in a hospital unless there is concern for rapid deterioration or an inability to return to hospital promptly.[139]
Advise patients and household members to follow appropriate infection prevention and control measures:
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).[139] The Centers for Disease Control and Prevention (CDC) recommends discontinuing home isolation once at least 10 days (or up to 20 days in patients who are severely immunocompromised) have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing home isolation once at least 10 days have passed since the date of a positive test. For severely immunocompromised patients who are asymptomatic, isolation may be discontinued when at least 10 days and up to 20 days have passed since the date of a positive test; consider consultation with infectious diseases specialists and infection control experts. Alternatively, the CDC recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred; however, a test-based strategy can be considered in severely immunocompromised patients.[732] If the patient is hospitalized, CDC guidance for discontinuing isolation is the same as for moderate disease (see below). Guidance on when to stop isolation depends on local recommendations and may differ between countries. For example, in the UK the isolation period is 10 days in patients with milder disease who are managed in the community.[733]
Treatment recommended for ALL patients in selected patient group
Closely monitor patients with risk factors for severe illness and counsel patients about signs and symptoms of deterioration or complications that require prompt urgent care (e.g., difficulty breathing, chest pain).[139][501]
Pulse oximetry monitoring at home is recommended in symptomatic patients with risk factors for progression to severe disease who are not hospitalized. Patient education and appropriate follow-up are required.[139]
Treatment recommended for ALL patients in selected patient group
Advise patients to avoid lying on their back as this makes coughing ineffective. Use simple measures first (e.g., a teaspoon of honey in patients ages 1 year and older) to help cough.[538] 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.[741]
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.[139][538]
Advise patients to improve air circulation by opening a window or door.[538]
Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate.[139]
Consider treatment for olfactory dysfunction (e.g., olfactory training) if it persists beyond 2 weeks. There is no evidence to support the use of these treatments in patients with COVID-19.[742]
Most children with mild disease can be managed with supportive care alone.[501]
Treatment recommended for SOME patients in selected patient group
Primary options
acetaminophen: children: 10-15 mg/kg orally every 4-6 hours when required, maximum 75 mg/kg/day; adults: 325-1000 mg orally (immediate-release) every 4-6 hours when required, maximum 4000 mg/day
OR
ibuprofen: children 6 months to 11 years of age: 5-10 mg/kg orally every 6-8 hours when required, maximum 40 mg/kg/day; children ≥12 years of age and adults: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day
Acetaminophen or ibuprofen are recommended.[139][538] 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.[734][735][736][737][738][739][740]
Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms. It is not recommended in pregnant women (especially in the third trimester) or children <6 months of age (age cut-offs vary by country).
Treatment recommended for SOME patients in selected patient group
Consider appropriate experimental or emerging therapies.
Antiviral therapies will have a greater effect early in the course of the disease, whereas immunosuppressive/anti-inflammatory therapies are likely to have a greater effect later in the course of the disease.[501]
See the Emerging section for more information.
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.[139]
Manage patients in a healthcare facility, in a community facility, or at home. Home isolation, with telemedicine or remote visits as appropriate, can be considered in low-risk patients. Manage patients at high risk of deterioration and pregnant women in a healthcare facility.[139][501]
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:
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.[139] The Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 10 days (not severely immunocompromised) or up to 20 days (severely immunocompromised) have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. In asymptomatic people, the CDC recommends discontinuing isolation once at least 10 days (not severely immunocompromised) or up to 20 days (severely immunocompromised) have passed since the date of a positive test. Severely immunocompromised patients may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts before discontinuing isolation. Alternatively, the CDC recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred; however, a test-based strategy can be considered in severely immunocompromised patients.[746] If the patient is isolated at home, CDC guidance for discontinuing isolation is the same as for mild disease (see above). Guidance on when to stop isolation depends on local recommendations and may differ between countries. For example, in the UK the isolation period is 14 days from a positive test in hospitalized 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.[733]
Treatment recommended for ALL patients in selected patient group
Closely monitor patients for signs or symptoms of disease progression. If the patient is being managed at home, counsel them about signs and symptoms of deterioration or complications that require prompt urgent care (e.g., difficulty breathing, chest pain). Pulse oximetry monitoring at home is recommended in symptomatic patients with risk factors for progression to severe disease who are not hospitalized. Patient education and appropriate follow-up are required. 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.[139]
Treatment recommended for ALL patients in selected patient group
Advise patients to avoid lying on their back as this makes coughing ineffective. Use simple measures first (e.g., a teaspoon of honey in patients ages 1 year and older) to help cough.[538] 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.[741]
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.[139][538]
Advise patients to improve air circulation by opening a window or door.[538]
Provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia, depression, or anxiety as appropriate.[139]
Consider treatment for olfactory dysfunction (e.g., olfactory training) if it persists beyond 2 weeks. There is no evidence to support the use of these treatments in patients with COVID-19.[742]
Most children with moderate disease can be managed with supportive care alone.[501]
Treatment recommended for SOME patients in selected patient group
Consider empiric 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.[139][501][538] The regimen should be based on the clinical diagnosis, local epidemiology and susceptibility data, and local treatment guidelines.
Antibiotics may also be considered in older people (particularly those in long-term care facilities) and children <5 years of age to provide empiric antibiotic treatment for possible pneumonia.[139]
Do not offer an antibiotic for preventing secondary bacterial pneumonia in people with COVID-19.[538]
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.[538]
Treatment recommended for SOME patients in selected patient group
Primary options
acetaminophen: children: 10-15 mg/kg orally every 4-6 hours when required, maximum 75 mg/kg/day; adults: 325-1000 mg orally (immediate-release) every 4-6 hours when required, maximum 4000 mg/day
OR
ibuprofen: children 6 months to 11 years of age: 5-10 mg/kg orally every 6-8 hours when required, maximum 40 mg/kg/day; children ≥12 years of age and adults: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day
Acetaminophen or ibuprofen are recommended.[139][538] 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.[734][735][736][737][738][739][740]
Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms. It is not recommended in pregnant women (especially in the third trimester) or children <6 months of age (age cut-offs vary by country).
Treatment recommended for SOME patients in selected patient group
Consider appropriate experimental or emerging therapies.
Antiviral therapies will have a greater effect early in the course of the disease, whereas immunosuppressive/anti-inflammatory therapies are likely to have a greater effect later in the course of the disease.[501]
See the Emerging section for more information.
Patients with suspected or confirmed severe disease are at risk of rapid clinical deterioration and should be admitted to an appropriate healthcare facility under the guidance of a specialist team. Severe disease in adults is defined as having clinical signs of pneumonia plus at least one of the following: respiratory rate >30 breaths/minute, severe respiratory distress, or SpO₂ <90% on room air. Severe disease in children is defined as having clinical signs of pneumonia plus at least one of the following: central cyanosis or SpO₂ <90%, severe respiratory distress, general danger signs (inability to breastfeed or drink, lethargy or unconsciousness, or convulsions), or fast breathing (<2 months: ≥60 breaths per minute; 2-11 months: ≥50 breaths per minute; 1-5 years: ≥40 breaths per minute).[139]
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, people with stable long-term disabilities (e.g., cerebral palsy), learning disabilities, or autism. Make an individualized assessment of frailty in these people, using clinical assessment and alternative scoring methods.[538] 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).[823] 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.[824]
Implement local infection prevention and control procedures when managing patients with COVID-19.
Pregnant women should be managed by a multidisciplinary team, including obstetric, perinatal, neonatal, and intensive care specialists, as well as midwifery and mental health and psychosocial support. A woman-centered, respectful, skilled approach to care is recommended.[139] 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.[808]
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.[139] The Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 10 days and up to 20 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. Consider consultation with infection control experts before discontinuing isolation. Severely immunocompromised patients may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts before discontinuing isolation. Alternatively, the CDC recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred; however, a test-based strategy can be considered in severely immunocompromised patients.[746] 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. 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.[733]
Treatment recommended for ALL patients in selected patient group
Start supplemental oxygen therapy immediately in any patient with emergency signs (i.e., obstructed or absent breathing, severe respiratory distress, central cyanosis, shock, coma and/or convulsions), or any patient without emergency signs and SpO₂ <90%.[139][501]
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.[139] Some guidelines recommend that SpO₂ should be maintained no higher than 96%.[750]
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 96% (or 90% to 94% if clinically appropriate), for example.[751]
Consider positioning techniques (e.g., high supported sitting), and airway clearance management to optimize oxygenation and 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.[139][501] Awake prone positioning of nonintubated patients was associated with improvement in oxygen variables (PaO₂/FiO₂, PaO₂, and SpO₂) and respiratory rate; however, evidence is limited. Further randomized controlled trials are required to study the impact on key parameters (e.g., reduction in mechanical ventilation or mortality).[752]
Monitor patients closely for signs of progressive acute hypoxemic respiratory failure.[139][501]
Treatment recommended for ALL patients in selected patient group
Fluids and electrolytes: use cautious fluid management in adults and children without tissue hypoperfusion and fluid responsiveness as aggressive fluid resuscitation may worsen oxygenation.[139] Correct any electrolyte or metabolic abnormalities, such as hyperglycemia or metabolic acidosis, according to local protocols.[753]
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 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.[538] 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.[741]
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, pulmonary embolism, COPD, asthma). Consider a trial of oxygen, if available.[538]
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).[139][538] Low doses of haloperidol (or another suitable antipsychotic) can be considered for agitation.[139] Nonpharmacologic interventions are the mainstay for the management of delirium when possible, and prevention is key.[754]
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.[755]
Mental health symptoms: provide basic mental health and psychosocial support for all patients, and manage any symptoms of insomnia or depression as appropriate.[139]
Treatment recommended for ALL patients in selected patient group
Primary options
enoxaparin: consult specialist for guidance on dose
OR
dalteparin: consult specialist for guidance on dose
Secondary options
fondaparinux: consult specialist for guidance on dose
OR
heparin: consult specialist for guidance on dose
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.[538]
Start venous thromboembolism (VTE) prophylaxis in acutely ill hospitalized adults and adolescents, provided there are no contraindications.[139][501][756][757] The UK National Institute for Health and Care Excellence (NICE) recommends starting as soon as possible and within 14 hours of admission, and continuing for a minimum of 14 days or until discharge.[538] For hospitalized children, indications for VTE prophylaxis should be the same as those for children without COVID-19.[501]
Low molecular weight heparin, unfractionated heparin, or fondaparinux are the recommended options for standard thromboprophylaxis.[139] NICE recommends low molecular weight heparin first-line, with fondaparinux or unfractionated heparin reserved for patients who cannot have low molecular weight heparin.[538] 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.[757][759]
The optimal dose is yet to be determined. Standard prophylaxis doses are generally recommended over intermediate- or full treatment-dose regimens in patients without an established indication for higher-dose anticoagulation. 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.[139] NICE recommends clinicians consider a treatment dose of a low molecular weight heparin in young people and adults who are likely to be in hospital for at least 3 days and need supplemental oxygen (but who are not yet receiving high-flow oxygen, continuous positive airway pressure, noninvasive ventilation, or invasive mechanical ventilation), unless contraindicated. This is because of fewer deaths and less likelihood of needing intensive care with this dose compared with a standard prophylaxis dose without a notable increase in major bleeding, although the evidence for this recommendation is weak. Treatment should be for a minimum of 14 days or until discharge, and the dose may need to be reduced if the clinical circumstances change (such as a need for advanced respiratory support). For those who do not need supplemental oxygen, follow standard VTE prophylaxis guidelines.[538] 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.[501]
Dose adjustments may be required in patients with extremes of body weight or renal impairment.[538]
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 as the preferred option for venous thromboembolism prophylaxis if the patient’s clinical condition is deteriorating and the patient is not currently on low molecular weight heparin.[538]
Monitor patients for signs and symptoms suggestive of thromboembolism and proceed with appropriate diagnostic and management pathways if clinically suspected.[139] If the patient’s clinical condition changes, assess the risk of VTE, reassess the bleeding risk, and review VTE prophylaxis.[538]
Continue until hospital discharge.[139] Routine post-discharge VTE prophylaxis is not generally recommended, except in certain high-risk patients.[501][756][757] Ensure patients who require VTE prophylaxis after discharge are able to use it correctly or have arrangements made for someone to help them.[538]
There is currently insufficient evidence to determine the risks and benefits of prophylactic anticoagulation in hospitalized patients with COVID-19.[760] A systematic review and meta-analysis found that the pooled odds of mortality between anticoagulated and nonanticoagulated hospitalized 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.[761] Clinicians should rely on pre-COVID-19 evidence-based principles of anticoagulation management combined with rational approaches to address clinical challenges.[756]
Treatment recommended for ALL patients in selected patient group
Monitor patients closely for signs of clinical deterioration, and respond immediately with appropriate supportive care interventions.[139]
Treatment recommended for SOME patients in selected patient group
Consider empiric 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.[139][501][538]
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.[538] There is insufficient evidence to recommend empiric broad-spectrum antibiotics in the absence of another indication.[501]
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 microbiologic evidence of infection and the person's condition does not improve as expected after 48 to 72 hours of antibiotic treatment.[538]
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.[139]
Treatment recommended for SOME patients in selected patient group
Primary options
dexamethasone: children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days
OR
hydrocortisone: children: consult specialist for guidance on dose; adults: 50 mg orally/intravenously every 8 hours for 7-10 days
Secondary options
prednisone: children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days
OR
methylprednisolone: children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days
The World Health Organization (WHO) strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with severe COVID-19. This recommendation is based on two meta-analyses that pooled data from eight 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 COVID-19. They also probably reduce the need for invasive ventilation. There is no evidence directly comparing dexamethasone and hydrocortisone. The harms of treatment in this context are considered to be minor. It is unclear whether these recommendations can be applied to children or those who are immunocompromised.[722][763][764][765][766] There is also evidence that corticosteroids probably increase ventilator-free days (moderate certainty).[767][825]
In the UK, the National Institute for Health and Care Excellence recommends offering dexamethasone (or an alternative such as hydrocortisone or prednisone 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.[538]
In Europe, the European Medicines Agency has endorsed the use of dexamethasone for patients with severe disease who require oxygen therapy or mechanical ventilation.[769]
In the US, the National Institutes of Health guidelines panel recommends dexamethasone, either alone or in combination with remdesivir (see the Emerging section for information on remdesivir), in hospitalized adults who require supplemental oxygen. The panel recommends against using dexamethasone in adults who do not require supplemental oxygen. Alternative corticosteroids may be used in situations where dexamethasone is not available. It is not routinely recommended for pediatric 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.[501] The Infectious Diseases Society of America supports the use of dexamethasone in hospitalized patients with severe disease.[770]
Monitor patients for adverse effects (e.g., hyperglycemia, secondary infections, psychiatric effects, reactivation of latent infections) and assess for drug-drug interactions.[501]
Treatment recommended for SOME patients in selected patient group
Treat laboratory-confirmed coinfections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[139] The treatment of influenza is the same in all patients regardless of SARS-CoV-2 coinfection. Start empiric treatment with oseltamivir in hospitalized 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.[501]
Treatment recommended for SOME patients in selected patient group
Primary options
acetaminophen: children: 10-15 mg/kg orally every 4-6 hours when required, maximum 75 mg/kg/day; adults: 325-1000 mg orally (immediate-release) every 4-6 hours when required, maximum 4000 mg/day
OR
ibuprofen: children 6 months to 11 years of age: 5-10 mg/kg orally every 6-8 hours when required, maximum 40 mg/kg/day; children ≥12 years of age and adults: 200-400 mg orally every 4-6 hours when required, maximum 2400 mg/day
Acetaminophen or ibuprofen are recommended.[139][538] 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.[734][735][736][737][738][739][740]
Ibuprofen should only be taken at the lowest effective dose for the shortest period needed to control symptoms. It is not recommended in pregnant women (especially in the third trimester) or children <6 months of age (age cut-offs vary by country).
Treatment recommended for SOME patients in selected patient group
Consider appropriate experimental or emerging therapies.
Antiviral therapies will have a greater effect early in the course of the disease, whereas immunosuppressive/anti-inflammatory therapies are likely to have a greater effect later in the course of the disease.[501]
See the Emerging section for more information.
Treatment recommended for SOME patients in selected patient group
Routinely assess older patients for mobility, functional swallow, cognitive impairment, and mental health concerns, and based on that assessment determine whether the patient is ready for discharge, and whether the patient has any rehabilitation and follow-up requirements.[139]
Treatment recommended for SOME patients in selected patient group
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.[139] 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 under the guidance of a specialist team.[139]
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.[538]
Implement local infection prevention and control procedures when managing patients with COVID-19.
Pregnant women should be managed by a multidisciplinary team, including obstetric, perinatal, neonatal, and intensive care specialists, as well as midwifery and mental health and psychosocial support. A woman-centered, respectful, skilled approach to care is recommended.[139] 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.[808]
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.[139] The Centers for Disease Control and Prevention (CDC) recommends discontinuing isolation once at least 10 days and up to 20 days have passed since symptoms first appeared, and at least 24 hours have passed since last fever without the use of antipyretics, and symptoms have improved, if a symptom-based strategy is used. Consider consultation with infection control experts before discontinuing isolation. Severely immunocompromised patients may produce replication-competent virus beyond 20 days and require additional testing and consultation with infectious diseases specialists and infection control experts before discontinuing isolation. Alternatively, the CDC recommends at least two negative reverse-transcription polymerase chain reaction (RT-PCR) tests on respiratory specimens collected 24 hours apart before ending isolation if a test-based strategy is used. A symptom-based strategy is preferred; however, a test-based strategy can be considered in severely immunocompromised patients.[746] 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. 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.[733]
Treatment recommended for ALL patients in selected patient group
Consider fluid and electrolyte management, antimicrobial treatment, and symptom management as appropriate. See Severe COVID-19 above for more detailed information.
Follow local guidelines for the management of pain, sedation, and delirium.[501]
Implement standard interventions to prevent complications associated with critical illness.[139]
Treatment recommended for ALL patients in selected patient group
Primary options
enoxaparin: consult specialist for guidance on dose
OR
dalteparin: consult specialist for guidance on dose
Secondary options
heparin: consult specialist for guidance on dose
OR
fondaparinux: consult specialist for guidance on dose
Unfractionated heparin is preferred over fondaparinux in critically ill patients if low molecular weight heparin, as the preferred option for venous thromboembolism prophylaxis, cannot be used.[757]
The UK National Institute for Health and Care Excellence (NICE) does not recommend treatment-dose low molecular weight heparin for VTE prophylaxis for patients receiving advanced respiratory support unless the patient is part of a nationally approved clinical trial because it is likely to cause harm in this group. NICE recommends reducing the dose to a locally agreed intermediate or standard dose and reassessing VTE and bleeding risks daily in patients who progress to needing high-flow oxygen, continuous positive airway pressure, noninvasive or invasive mechanical ventilation, or palliative care.[538]
NHS England recommends that therapeutic doses should not be offered unless there is a standard indication for therapeutic anticoagulation, as trials show that therapeutic doses do not improve clinical outcome of severe disease in the critical care setting.[804]
Some guidelines recommend that escalated doses can be considered in critically ill patients.[756][805]
A multicenter randomized 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 empiric use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the intensive care unit.[806]
Dose adjustments may be required in patients with extremes of body weight or renal impairment.[538]
See Severe COVID-19 above for more detailed information on VTE prophylaxis.
Treatment recommended for ALL patients in selected patient group
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. Consider awake prone positioning (for 8-12 hours/day, broken into shorter periods over the day) in severely ill patients who require HFNO or noninvasive ventilation.[139] Awake prone positioning of nonintubated patients was associated with improvement in oxygen variables (PaO₂/FiO₂, PaO₂, and SpO₂) and respiratory rate; however, evidence is limited. Further randomized controlled trials are required to study the impact on key parameters (e.g., reduction in mechanical ventilation or mortality).[752]
Airborne precautions are recommended for these interventions (including bubble CPAP) due to uncertainty about the potential for aerosolization.[139]
Patients with hypercapnia, hemodynamic instability, multi-organ failure, or abnormal mental status should generally not receive HFNO, although emerging data suggest that it may be safe in patients with mild to moderate and 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.[139]
There is ongoing debate about the optimal mode of respiratory support before mechanical ventilation.[775] 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.[776] Other guidelines recommend HFNO over noninvasive ventilation, unless HFNO is not available.[501][750] Despite the trend to avoid HFNO, it has been shown to have a similar risk of aerosol generation to standard oxygen masks.[777]
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).[776]
Monitor patients closely for acute deterioration. If patients do not improve after a short trial of these interventions, they require urgent endotracheal intubation.[139][750]
Treatment recommended for ALL patients in selected patient group
Consider endotracheal intubation and mechanical ventilation in patients who are acutely deteriorating despite advanced oxygen/noninvasive ventilatory support measures.[139][501]
Endotracheal intubation should be performed by an experienced provider using airborne precautions.[139] Intubation by video laryngoscopy is recommended if possible.[501] Young children, or adults who are obese or pregnant, may desaturate quickly during intubation and therefore require preoxygenation with 100% fraction of inspired oxygen (FiO₂) for 5 minutes.[139]
Mechanically ventilated patients with acute respiratory distress syndrome (ARDS) should receive a lung-protective, low tidal volume/low inspiratory pressure ventilation strategy (lower targets are recommended in children). A higher positive end-expiratory pressure (PEEP) strategy is preferred over a lower PEEP strategy in moderate to severe ARDS. However, 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.[139][501][750] NHS England recommends a low PEEP strategy in patients with normal compliance where recruitment may not be required.[785]
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.[786][787][788][789][790][791] However, this approach has been criticized.[792][793] 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.[794] 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.[786] PEEP should always be carefully titrated.[795]
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.[139][501][750] Longer durations may be feasible in some patients.[796]
Lung recruitment maneuvers are suggested, but staircase recruitment maneuvers are not recommended.[501][750]
Treatment recommended for SOME patients in selected patient group
Consider extracorporeal membrane oxygenation (ECMO) according to availability and expertise if the above methods fail.[139][750][797][798] ECMO is not suitable for all patients, and only those who meet certain inclusion criteria may be considered for ECMO.[799]
There is insufficient evidence to recommend either for or against the routine use of ECMO.[501]
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 in one study.[800]
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.[801]
A multicenter cohort study in France reported a 90-day survival rate of 46%. Factors associated with improved 90-day survival included earlier ECMO initiation, younger age, no pre-ECMO renal dysfunction, and treatment in centers managing at least 30 venovenous ECMO cases annually.[802]
Single-access, dual-stage venovenous ECMO with early extubation appears to be safe and effective in patients with COVID-19 respiratory failure.[803]
Treatment recommended for SOME patients in selected patient group
The management of sepsis and septic shock in patients with COVID-19 is beyond the scope of this topic. See the Complications section.
Treatment recommended for SOME patients in selected patient group
Primary options
dexamethasone: children: consult specialist for guidance on dose; adults: 6 mg orally/intravenously once daily for 7-10 days
OR
hydrocortisone: children: consult specialist for guidance on dose; adults: 50 mg orally/intravenously every 8 hours for 7-10 days
Secondary options
prednisone: children: consult specialist for guidance on dose; adults: 40 mg/day orally given in 1-2 divided doses for 7-10 days
OR
methylprednisolone: children: consult specialist for guidance on dose; adults: 32 mg/day orally/intravenously given in 1-2 divided doses for 7-10 days
The World Health Organization (WHO) strongly recommends systemic corticosteroid therapy (low-dose intravenous or oral dexamethasone or hydrocortisone) for 7 to 10 days in adults with critical COVID-19. This recommendation is based on two meta-analyses that pooled data from eight 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 COVID-19. They also probably reduce the need for invasive ventilation. There is no evidence directly comparing dexamethasone and hydrocortisone. The harms of treatment in this context are considered to be minor. It is unclear whether these recommendations can be applied to children or those who are immunocompromised.[722][763][764][765][766] There is also evidence that corticosteroids probably increase ventilator-free days (moderate certainty).[767][825]
In the UK, the National Institute for Health and Care Excellence recommends offering dexamethasone (or an alternative such as hydrocortisone or prednisone 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.[538]
In Europe, the European Medicines Agency has endorsed the use of dexamethasone for patients with severe disease who require oxygen therapy or mechanical ventilation.[769]
In the US, the National Institutes of Health guidelines panel recommends using dexamethasone, either alone or in combination with remdesivir (see the Emerging section for information on remdesivir), in hospitalized patients who require high-flow oxygen or noninvasive ventilation. The panel recommends dexamethasone (in combination with tocilizumab - see the Emerging section for information on tocilizumab) in patients on mechanical ventilation or extracorporeal membrane oxygenation. Alternative corticosteroids may be used in situations where dexamethasone is not available. The panel recommends using dexamethasone in hospitalized children who require high-flow oxygen, noninvasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation.[501] The Infectious Diseases Society of America supports the use of dexamethasone in hospitalized patients with severe disease.[770]
Monitor patients for adverse effects (e.g., hyperglycemia, secondary infections, psychiatric effects, reactivation of latent infections) and assess for drug-drug interactions.[501]
A meta-analysis found an increased risk of venous thromboembolism 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.[807]
Treatment recommended for SOME patients in selected patient group
Treat laboratory-confirmed coinfections (e.g., malaria, tuberculosis, influenza) as appropriate according to local protocols.[139] The treatment of influenza is the same in all patients regardless of SARS-CoV-2 coinfection. Start empiric treatment with oseltamivir in hospitalized 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.[501]
Treatment recommended for SOME patients in selected patient group
Consider appropriate experimental or emerging therapies.
Antiviral therapies will have a greater effect early in the course of the disease, whereas immunosuppressive/anti-inflammatory therapies are likely to have a greater effect later in the course of the disease.[501]
See the Emerging section for more information.
Treatment recommended for SOME patients in selected patient group
Routinely assess intensive care patients for mobility, functional swallow, cognitive impairment, and mental health concerns, and based on that assessment determine whether the patient is ready for discharge, and whether the patient has any rehabilitation and follow-up requirements.[139]
Treatment recommended for SOME patients in selected patient group
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.[139] Follow local palliative care guidelines.
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