Interim Clinical Considerations for COVID-19 Treatment in Outpatients
This page provides a treatment overview for healthcare providers.
For General Public: COVID-19 Treatments and Medications
- There is strong scientific evidence that antiviral treatment of outpatients at risk for severe COVID-19 reduces their risk of hospitalization and death.
- The antiviral drugs nirmatrelvir with ritonavir (Paxlovid) and remdesivir (Veklury) are the preferred treatments for eligible adult and pediatric patients who are at high risk for progression to severe COVID-19.
- Clinicians should consider COVID-19 treatment in patients with mild-to-moderate COVID-19 who have one or more risk factors for severe COVID-19. Treatment must be started early to be effective.
Risk Factors for Severe COVID-19
Clinicians can use the links below to identify patients at risk for severe COVID-19 and who may benefit from outpatient treatment. Severe outcomes of COVID-19 are defined as hospitalization, intensive care, ventilatory support, or death. There may be other medical conditions associated with severe COVID-19 not listed here, and clinical judgment is needed.
Age is the most important risk factor for severe outcomes of COVID-19.
Risk factors for severe COVID-19 include:
- Age over 50 years, with risk increasing substantially at age ≥ 65 years
- Being unvaccinated or not being up to date on COVID-19 vaccinations
- Specific medical conditions and behaviors
Some people from racial and ethnic minority groups are at risk of being disproportionately affected by COVID-19 from many factors, including limited access to vaccines and healthcare.(1-3) Healthcare providers can consider these factors when evaluating the risk for severe COVID-19 and use of outpatient therapeutics.
Outpatient Treatments for COVID-19
Oral nirmatrelvir with ritonavir (Paxlovid)
In a clinical trial, Paxlovid reduced the risk of hospitalization and death by 89% in unvaccinated outpatients with COVID-19 at higher risk of severe disease.(4) Serious adverse events are uncommon with Paxlovid treatment.(4) Paxlovid is given twice daily for 5 days, starting as soon as possible and within 5 days of symptom onset, and is approved for use in adult and pediatric patients (12 years of age and older weighing at least 40kg). Clinicians should be aware of the eligibility criteria and the potential for drug interactions with the use of Paxlovid that may preclude Paxlovid use or may require temporary discontinuation of other medications.
COVID-19 rebound has been reported to occur in a small percentage of patients between 2 and 8 days after initial recovery and is characterized by recurrent but milder symptoms and viral detection after having tested negative. For more information about viral rebound and the recurrence of COVID-19 symptoms, refer to the NIH COVID-19 Treatment Guidelines: Ritonavir-Boosted Nirmatrelvir (Paxlovid).
Intravenous remdesivir (Veklury)
Remdesivir (Veklury) reduced the risk of hospitalization and death by 87% in unvaccinated outpatients with COVID-19 at higher risk of severe disease.(5) A 3-day course of intravenous remdesivir initiated within 7 days of symptom onset is the second preferred treatment option after Paxlovid for adults and pediatric patients (age >28 days and weight > 3kg).
When Paxlovid or remdesivir are not accessible or clinically appropriate, the oral antiviral molnupiravir can be used.(6-7) Clinicians can use the link below to review details on eligibility and indication.
The U.S. Food and Drug Administration (FDA) has also issued an Emergency Use Authorization (EUA) to permit the emergency use of COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies for the treatment of COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive treatment, in either the outpatient or inpatient setting. For more information, please see the FDA Fact Sheet for Providers. The NIH COVID-19 Treatment Guidelines, also provide recommendations on who should be considered for this treatment.
All patients with symptomatic COVID-19 should be offered symptom management with over-the-counter antipyretics, analgesics, or antitussives for fever, headache, myalgias, and cough.(7)
For Healthcare Providers
- Clinical Decision Aid for COVID-19 Outpatient Therapeutics
- Side-by-Side Overview of Outpatient Therapeutics
- NIH Treatment Guidelines for Non-Hospitalized Adults
- FDA List of Current COVID-19 Emergency Use Authorization Products
- Outpatient COVID-19 Therapeutics Administration Guide
- COVID-19 Therapeutics Locator
- Clinical Considerations for Children and Adults with Confirmed COVID-19
- FDA Approval for Remdesivir
- Prescribing Information for Remdesivir
- Emergency Use Authorization (EUA) of COVID-19 convalescent plasma for treatment of Coronavirus Disease 2019 (COVID-19)
- NIH COVID-19 Treatment Guidelines: COVID-19 Convalescent Plasma
- Garg S, Kim L, Whitaker M, O’Halloran A, Cummings C, Holstein R, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr 17;69(15):458–64. doi: 10.15585/mmwr.mm6915e3
- Romano SD, Blackstock AJ, Taylor EV, El Burai Felix S, Adjei S, Singleton CM, et al. Trends in Racial and Ethnic Disparities in COVID-19 Hospitalizations, by Region — United States, March–December 2020. MMWR Morb Mortal Wkly Rep. 2021 Apr 16;70(15):560–5. doi: 10.15585/mmwr.mm7015e2
- Gold JAW, Rossen LM, Ahmad FB, Sutton P, Li Z, Salvatore PP, et al. Race, Ethnicity, and Age Trends in Persons Who Died from COVID-19 — United States, May–August 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct 23;69(42):1517–21. doi: 10.15585/mmwr.mm6942e1
- Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19. N Engl J Med. 2022 Apr 14;386(15):1397–408. doi: 10.1056/NEJMoa2118542
- Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305–15. doi: 10.1056/NEJMoa2116846
- Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022 Feb 10;386(6):509–20. doi: 10.1056/NEJMoa2116044
- Levin MJ, Ustianowski A, De Wit S, et al. Intramuscular AZD7442 (Tixagevimab–Cilgavimab) for Prevention of Covid-19. N Engl J Med. Published June 9, 2022:NEJMoa2116620. doi:10.1056/NEJMoa2116620
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