COVID-19 Treatment Clinical Care for Outpatients

Key points

  • Clinicians should consider COVID-19 treatment in patients with mild or moderate COVID-19 who have one or more risk factors for severe COVID-19 to reduce progression to hospitalization and death.
  • Treatment must be started as soon as possible and within 5-7 days of symptom onset.
  • Pre-exposure prophylaxis (prevention) medication is available for some people who are moderately or severely immunocompromised for additional protection against COVID-19.
Patient talking to doctor.

Who qualifies for treatment

Patients who are at higher risk for severe COVID-19 might benefit from outpatient treatment. Severe outcomes of COVID-19 include hospitalization, intensive care, ventilatory support, or death.

Risk Factor‎

Age is the most important risk factor for severe outcomes of COVID-19.

Risk factors for severe COVID-19 include:

There may be other factors, such as a patient being a resident of a long-term care facility, associated with severe COVID-19 not listed here, and clinical judgment is needed to accurately assess a person’s risk on a case-by-case basis.

Some racial and ethnic minority groups are disproportionately affected by COVID-19 because of many factors, including limited access to vaccines and healthcare.123

More details: Actions Healthcare Providers Can Take for Patients at Higher Risk of Severe COVID-19

Treatment options for COVID-19

Did you know?‎

Patient assistance programs providing low and no-cost access to COVID-19 therapeutics are available to patients who are underinsured, uninsured, and who are on Medicare or Medicaid. Patients should enroll in a program to learn if they can receive assistance for specific medications, regardless of their insurance status. Providers and clinicians should review the commercialization guide for more information on ordering and distribution timelines and patient assistance programs. COVID-19 medications can be located online.

Oral ritonavir-boosted nirmatrelvir (Paxlovid)

In a clinical trial, ritonavir-boosted nirmatrelvir reduced the risk of hospitalization and death by 87% in unvaccinated outpatients with COVID-19 at higher risk of severe disease. Serious adverse events are uncommon with Paxlovid treatment.4

Similar results were observed in patients with prior immunity to the virus that causes COVID-19.

Several real-world studies examining outcomes following ritonavir-boosted nirmatrelvir use for mild or moderate COVID-19 have demonstrated reduced risk of hospitalization and death in the Omicron era.5

Ritonavir-boosted nirmatrelvir is given twice daily for 5 days, starting as soon as possible and within 5 days of symptom onset. It is approved for use in adults and authorized for use in pediatric patients (12 years of age and older weighing at least 88 pounds [40 kilograms]). Guidelines suggest that clinicians may recommend longer or additional courses of ritonavir-boosted nirmatrelvir for immunocompromised patients who continue experiencing COVID-19 symptoms after receiving antiviral treatment.

Clinicians should be aware of the eligibility criteria and the potential for drug interactions with the use of ritonavir-boosted nirmatrelvir that may preclude ritonavir-boosted nirmatrelvir use or may require temporary discontinuation of other medications. Nirmatrelvir/ritonavir drug resistance is not typically associated with viral RNA rebound.

Learn more about COVID-19 rebound below.

Intravenous remdesivir (Veklury)

Remdesivir (Veklury) reduced the risk of hospitalization and death by 87% in unvaccinated outpatients with COVID-19 who are at higher risk of severe disease. A 3-day course of intravenous remdesivir initiated within 7 days of symptom onset is the second preferred treatment option after ritonavir-boosted nirmatrelvir for adults and pediatric patients (age >28 days and weight > 6.6 pounds [> 3 kilograms]).

Clinicians may recommend longer or additional courses of remdesivir for immunocompromised patients who continue experiencing COVID-19 symptoms after receiving viral treatment.

Remdesivir is also approved for use in patients with mild to severe hepatic impairment. For more information on remdesivir, refer to Remdesivir Approved Label [PDF – 44 pages]

Alternative Therapies

When ritonavir-boosted nirmatrelvir or remdesivir are not accessible or clinically appropriate, the oral antiviral molnupiravir can be used. 67 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. Clinicians may recommend longer or additional courses of convalescent plasma for immunocompromised patients who continue experiencing COVID-19 symptoms after receiving antiviral treatment. 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.

Symptomatic Management‎

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

Care Timeline

Preventing COVID-19 with Pre-exposure Prophylaxis

Pre-exposure prophylaxis (prevention) medication is available for some people who are moderately or severely immunocompromised for additional protection against COVID-19.

Pemivibart (Pemgarda™) is a monoclonal antibody for COVID-19 pre-exposure prophylaxis in people who are moderately or severely immunocompromised and unlikely to mount an adequate immune response to COVID-19 vaccination and who meet the FDA-authorized conditions for use. Pemivibart may provide another layer of protection against COVID-19 in addition to the protection provided through vaccination and can be given at least 2 weeks after receiving a dose of COVID-19 vaccine. Pemivibart is administered as a single intravenous infusion over 60 minutes at a healthcare facility. If continued protection is needed, additional doses should be administered every 3 months. Pemivibart is still being studied and there is limited information about the safety and effectiveness of pemivibart in preventing COVID-19.

Pre-exposure prophylaxis helps prevent COVID-19 but does not take the place of vaccination in people who are eligible to receive an updated COVID-19 vaccine. Everyone ages 6 months and older should stay up-to-date with COVID-19 vaccine. For more information, please see the FDA Fact Sheet for Providers.

Returning Symptoms: COVID-19 Rebound

COVID-19 rebound [PDF – 4 pages] is characterized by a recurrence of symptoms after recovery or a new positive test after having tested negative for SARS-CoV-2, the virus that causes COVID-19. Rebound has been reported to occur in some patients, including those treated with antivirals and those who did not take treatment. Current evidence suggests rebound presents as mild symptoms 3-7 days after initial illness has resolved.8

Treatment benefits outweigh the risks of rebound for patients at higher risk for severe disease from COVID-19.

People who develop rebound should isolate to prevent further transmission.

Resources

Names of specific vendors, manufacturers, or products in this collection of content are included for public health and informational purposes; inclusion does not imply endorsement of the vendors, manufacturers, or products by the Centers for Disease Control and Prevention or the US Department of Health and Human Services.

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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)
  1. 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
  2. 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
  3. 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
  4. 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
  5. Amani, B., & Amani, B. (2023). Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID-19: A rapid review and meta-analysis. Journal of medical virology, 95(2), e28441. https://doi.org/10.1002/jmv.28441
  6. 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
  7. 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
  8. CDC – Respiratory Illnesses – What's New – If You Get Sick with COVID-19, Antivirals Can Protect You Against Severe Illness: 9 Key Things to Know About Antivirals. https://www.cdc.gov/respiratory-viruses/whats-new/antiviral-treatments.html. December 21, 2023.