Important update: Healthcare facilities
CDC has updated select ways to operate healthcare systems effectively in response to COVID-19 vaccination. Learn more
Given new evidence on the B.1.617.2 (Delta) variant, CDC has updated the guidance for fully vaccinated people. CDC recommends universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status. Children should return to full-time in-person learning in the fall with layered prevention strategies in place.
The White House announced that vaccines will be required for international travelers coming into the United States, with an effective date of November 8, 2021. For purposes of entry into the United States, vaccines accepted will include FDA approved or authorized and WHO Emergency Use Listing vaccines. More information is available here.

Interim Clinical Considerations for COVID-19 Treatment in Outpatients

Interim Clinical Considerations for COVID-19 Treatment in Outpatients
Updated Jan. 17, 2024

This page provides a treatment overview for healthcare providers.

For General Public: COVID-19 Treatments and Medications

What You Need to Know
  • There is strong scientific evidence that antiviral treatment of persons with mild to moderate illness who are at risk for severe COVID-19 reduces their risk of hospitalization and death.
  • The antiviral drugs ritonavir-boosted nirmatrelvir (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 as soon as possible and within 5-7 days of symptom onset.

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 to accurately assess a person’s risk.

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

Age is the most important risk factor for severe outcomes of COVID-19. Risk factors for severe COVID-19 include:

Some racial and ethnic minority groups are disproportionately affected by COVID-19 because of 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 therapeutics.

Outpatient Treatments for COVID-19

The United States government is ending its current ordering of COVID-19 oral antiviral treatments. Ritonavir-boosted nirmatrelvir (Paxlovid) and molnupiravir (Lagevrio) began transitioning to the commercial market on November 1, 2023. Ritonavir-boosted nirmatrelvir and molnupiravir will continue to be available during and after this transition to all eligible patients, including low and no-cost access for patients who are underinsured, uninsured, and who are on Medicare or Medicaid. All providers should ensure that they order sufficient product from the United States Government starting November 1, 2023, to meet expected demand during the transition. Providers and clinicians should review the commercialization transition guide for information on ordering and distribution timelines and patient assistance programs.

Oral ritonavir-boosted nirmatrelvir (Paxlovid)

In a clinical trial, ritonavir-boosted nirmatrelvir reduced the risk of hospitalization and death by 86% 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. Among patients in the EPIC-HR trial who were antibody positive at trial enrollment, the risk of COVID-19-related hospitalization or death from any cause during 28 days of follow-up was 0.2% among those treated with ritonavir-boosted nirmatrelvir compared with 1.7% of those receiving placebo.

Ritonavir-boosted nirmatrelvir 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 adults and authorized for use in pediatric patients (12 years of age and older weighing at least 40kg). 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.

COVID-19 Rebound

COVID-19 rebound [PDF – 4 pages] is characterized by a recurrence of symptoms or a new positive test after having tested negative for 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.

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 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 > 3kg). 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 NIH COVID-19 Treatment Guidelines: remdesivir (Veklury).

Alternative Therapies

When ritonavir-boosted nirmatrelvir 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. 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)


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