Therapeutic Management of Nonhospitalized Adults With COVID-19
Last Updated: October 19, 2021
Figure 1 outlines the COVID-19 Treatment Guidelines Panel’s (the Panel) recommendations for using therapeutic interventions outside the hospital inpatient setting. These recommendations differ depending on the patient’s disposition.
Symptomatic treatment includes using over-the-counter antipyretics, analgesics, or antitussives for fever, headache, myalgias, and cough. Patients with dyspnea may benefit from resting in the prone position rather than the supine position.1 Health care providers should consider educating patients about breathing exercises, as severe breathlessness may cause anxiety.2 Patients should be advised to drink fluids regularly to avoid dehydration. Rest is recommended as needed during the acute phase of COVID-19, and ambulation and other forms of activity should be increased according to the patient’s tolerance. Patients should be educated about the variability in time to symptom resolution and complete recovery.
Rationale for the Use of Specific Agents Listed in Figure 1
Anti-SARS-CoV-2 Monoclonal Antibodies
Two combination anti-SARS-CoV-2 monoclonal antibody (mAb) products (bamlanivimab plus etesevimab and casirivimab plus imdevimab) and a single mAb (sotrovimab) have been shown to reduce the risk of hospitalization and death in the outpatient setting in those with mild to moderate COVID-19 symptoms and certain risk factors for disease progression. As a result, these products have received Emergency Use Authorizations (EUAs) from the Food and Drug Administration (FDA) for the treatment of COVID-19 in these individuals, as well as in those with other risk factors for progression that have been identified in population-based studies. There are no comparative data to determine whether there are differences in clinical efficacy or safety between these products.
The Panel recommends using one of the following anti-SARS-CoV-2 mAbs to treat outpatients with mild to moderate COVID-19 who are at high risk of clinical progression, as defined by the EUA criteria (treatments are listed in alphabetical order, and they may change based on circulating variants):
- Bamlanivimab plus etesevimab; or
- Casirivimab plus imdevimab; or
The availability of bamlanivimab and etesevimab is restricted in areas with an elevated prevalence of variants that have markedly reduced in vitro susceptibility to these agents (e.g., the Gamma and Beta variants). Please see this statement from the Department of Health and Human Services for an update on the distribution of bamlanivimab and etesevimab.
The Delta (B.1.617.2, non-AY.1/AY.2) variant is currently the predominant variant of concern (VOC) in the United States. This VOC retains in vitro susceptibility to all the anti-SARS-CoV-2 mAbs that are currently available through EUAs.3,4
Treatment should be started as soon as possible after the patient receives a positive result on a SARS-CoV-2 antigen test or a nucleic acid amplification test (NAAT) and within 10 days of symptom onset. When logistical or supply constraints limit the availability of anti-SARS-CoV-2 mAbs, the Panel recommends prioritizing the treatment of patients who are at the highest risk of clinical progression (see the Panel’s statement on prioritizing the use of anti-SARS-CoV-2 mAbs). For more details on the available clinical trial data for these antibodies, see Anti-SARS-CoV-2 Monoclonal Antibodies and Table 3a.
The Centers for Disease Control and Prevention recommends deferring COVID-19 vaccination for at least 90 days in those who have received anti-SARS-CoV-2 mAbs. This is a precautionary measure, as the antibody treatment may interfere with vaccine-induced immune responses. In people who are vaccinated and then develop COVID-19, prior receipt of a vaccine should not affect treatment decisions, including the use of and timing of treatment with mAbs.5
The Panel recommends against the use of dexamethasone or other systemic glucocorticoids to treat outpatients with mild to moderate COVID-19 who do not require hospitalization or supplemental oxygen (AIII). There is currently a lack of safety and efficacy data on the use of these agents, and systemic glucocorticoids may cause harm in these patients. Patients who are receiving dexamethasone or another corticosteroid for other indications should continue therapy for their underlying conditions as directed by their health care providers (AIII).
In the RECOVERY trial, dexamethasone was shown to reduce mortality in hospitalized patients with COVID-19 who required supplemental oxygen. There was no observed benefit of dexamethasone in hospitalized patients who did not receive oxygen support.6 Nonhospitalized patients who did not require supplemental oxygen were not included in this trial; therefore, the safety and efficacy of corticosteroids in this population have not been established. The Panel recommends against the use of dexamethasone or other systemic glucocorticoids in this population, as there are no clinical trial data to support their use (AIII). Moreover, the use of corticosteroids can lead to adverse events (e.g., hyperglycemia, neuropsychiatric symptoms, secondary infections), which may be difficult to detect and monitor in an outpatient setting.
Dexamethasone was stopped at the time of hospital discharge during the RECOVERY trial. For hospitalized patients with COVID-19 who do not require supplemental oxygen after discharge, the Panel recommends against the continuation of dexamethasone (AIIa).
In some cases, adult patients are deemed to be stable enough to be discharged from the inpatient setting even though they still require supplemental oxygen. The practice of discharging inpatients who still require oxygen was likely uncommon during the RECOVERY trial; therefore, there is insufficient evidence to recommend either for or against the continued use of dexamethasone after hospital discharge in patients who require supplemental oxygen. Data that support the use of corticosteroids after discharge are limited. The main concern is that discharged patients cannot be closely monitored for the toxicities that are associated with corticosteroid use, which include increased blood glucose levels and neuropsychiatric impairment. If a patient continues to receive corticosteroids after discharge, consider continuing corticosteroids for the duration of supplemental oxygen. However, the total duration of corticosteroid use should not exceed 10 days (including days during hospitalization). Only patients who showed good tolerance to this therapy prior to discharge should continue to receive corticosteroids after discharge, and these patients should be carefully monitored for adverse events. These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
In rare cases, patients with COVID-19 who require supplemental oxygen and hospital admission may need to be discharged from the emergency department (ED) due to scarce resources (e.g., in cases where hospital beds or staff are not available). For these patients, the Panel recommends using dexamethasone 6 mg orally once daily for the duration of supplemental oxygen (dexamethasone use should not exceed 10 days) with careful monitoring for adverse events (BIII). These patients should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
Remdesivir is currently the only drug that is approved by the FDA for the treatment of COVID-19. It is recommended for use in hospitalized patients who require supplemental oxygen. The clinical trials that evaluated the safety and efficacy of remdesivir stopped this treatment at the time of discharge from the hospital.7-9 The Panel recommends against the continuation of remdesivir in hospitalized patients with COVID-19 who are stable enough for discharge and who do not require supplemental oxygen (AIIa).
In some cases, adult patients are deemed to be stable enough to be discharged from the inpatient setting even though they still require supplemental oxygen. There is insufficient evidence to recommend either for or against the continued use of remdesivir after hospital discharge in patients who require supplemental oxygen. Since remdesivir can only be administered by intravenous infusion, there may be logistical issues with providing remdesivir to outpatients. If remdesivir is provided, it should only be administered in health care settings that can provide a similar level of care to an inpatient hospital. These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
In rare cases, patients with COVID-19 who require supplemental oxygen and hospital admission may need to be discharged from the ED due to scarce resources (e.g., in cases where hospital beds or staff are not available). There is insufficient evidence to recommend either for or against the routine use of remdesivir in this setting. If remdesivir is provided, it should only be administered in health care settings that can provide a similar level of care to an inpatient hospital. These individuals should receive oximetry monitoring and close follow-up through telehealth, visiting nurse services, or in-person clinic visits.
The pivotal safety and efficacy trials for baricitinib enrolled hospitalized patients with COVID-19, and treatment was stopped at the time of hospital discharge.10,11 The Panel recommends against the continuation of baricitinib in hospitalized patients with COVID-19 who are stable enough for discharge and who do not require supplemental oxygen (AIIa).
There is insufficient evidence to recommend either for or against the continued use of baricitinib after hospital discharge in patients who have been discharged from the inpatient setting but who still require supplemental oxygen.
There are currently no data that assess the safety and efficacy of using baricitinib in patients who require supplemental oxygen and hospital admission, but who have been discharged from the ED due to scarce resources. Therefore, the Panel recommends against the use of baricitinib in these patients, except in a clinical trial (AIII).
Other Agents That Have Been Studied or Are Under Investigation for Use in Outpatients With COVID-19
- The Panel recommends against the use of chloroquine or hydroxychloroquine with or without azithromycin (AI), lopinavir/ritonavir, and other HIV protease inhibitors (AIII) for the outpatient treatment of COVID-19.
- The Panel recommends against the use of antibacterial therapy (e.g., azithromycin, doxycycline) for the outpatient treatment of COVID-19 in the absence of another indication (AIII).
- Other agents have undergone or are currently undergoing investigation in the outpatient setting. For more information, please refer to the sections of the Guidelines that address:
- Anticoagulants and antiplatelet therapy should not be initiated in the outpatient setting for the prevention of venous thromboembolism or arterial thrombosis unless the patient has other indications for the therapy or is participating in a clinical trial (AIII). For more information, see Antithrombotic Therapy in Patients With COVID-19.
- Health care providers should provide information about ongoing clinical trials of investigational therapies to eligible outpatients with COVID-19 so they can make informed decisions about participation (AIII).
Concomitant Medication Management
In general, a patient’s usual medication and/or supplement regimen should be continued after the diagnosis of COVID-19 (see Considerations for Certain Concomitant Medications in Patients With COVID-19). Angiotensin-converting enzyme inhibitors, statin therapy, nonsteroidal anti-inflammatory drugs, and oral, inhaled, and intranasal corticosteroids that are prescribed for comorbid conditions should be continued as directed (AIII). Patients should be advised to avoid the use of nebulized medications in the presence of others to avoid potential aerosolization of SARS-CoV-2.12 In patients with HIV, antiretroviral therapy should not be switched or adjusted for the purpose of preventing or treating SARS-CoV-2 infection (AIII). For more information, see Special Considerations in People With HIV.
When a patient is receiving an immunomodulating medication, the prescribing clinician should be consulted about the risks and benefits that are associated with a temporary dose reduction or discontinuation; these risks and benefits will depend on the medication’s indication and the severity of the underlying condition.
Patients who use a continuous positive airway pressure (CPAP) device or a bilevel positive airway pressure (BiPAP) device to manage obstructive sleep apnea may continue to use their machine. As with nebulizers, patients should be advised to use the device only when they are isolated from others.
- Caputo ND, Strayer RJ, Levitan R. Early self-proning in awake, non-intubated patients in the emergency department: a single ED's experience during the COVID-19 pandemic. Acad Emerg Med. 2020;27(5):375-378. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32320506.
- National Institute for Health and Care Excellence (NICE) in collaboration with NHS England and NHS Improvement. Managing COVID-19 symptoms (including at the end of life) in the community: summary of NICE guidelines. BMJ. 2020;369:m1461. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32312715.
- Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization (EUA) of bamlanivimab and etesevimab. 2021. Available at: https://www.fda.gov/media/145802/download.
- Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization (EUA) of REGEN-COV (casirivimab and imdevimab). 2021. Available at: https://www.fda.gov/media/145611/download.
- Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently authorized in the United States. 2021. Available at: https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html. Accessed September 16, 2021.
- RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with COVID-19. N Engl J Med. 2021;384(8):693-704. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32678530.
- Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19—final report. N Engl J Med. 2020;383(19):1813-1826. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32445440.
- Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 days in patients with severe COVID-19. N Engl J Med. 2020;383(19):1827-1837. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32459919.
- Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial. JAMA. 2020;324(11):1048-1057. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32821939.
- Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with COVID-19. N Engl J Med. 2021;384(9):795-807. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33306283.
- Marconi VC, Ramanan AV, de Bono S, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34480861.
- Cazzola M, Ora J, Bianco A, Rogliani P, Matera MG. Guidance on nebulization during the current COVID-19 pandemic. Respir Med. 2021;176:106236. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33248363.