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.
Travel requirements to enter the United States are changing, starting November 8, 2021. More information is available here.

Interim Clinical Considerations for COVID-19 Treatment in Outpatients

Interim Clinical Considerations for COVID-19 Treatment in Outpatients
Updated May 26, 2023

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 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 as soon as possible and within 5 days of symptom onset 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:

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 86% in unvaccinated outpatients with COVID-19 at higher risk of severe disease. 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 adults and authorized for use in 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).

Alternative Therapies

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.

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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