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.

To minimize delays in antiviral treatment for patients at higher risk for severe COVID-19, use a nucleic acid amplification test (NAAT), such as a PCR test, when possible for reliable diagnosis.

Risk Factor‎

Age is the most important risk factor for severe outcomes of COVID-19, with risk increasing substantially as age increases above 65 years.

Risk factors for severe COVID-19, such as illness requiring hospitilization, include:

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

Some racial and ethnic minority groups are disproportionately affected by COVID-19 because of many factors, including limited access to vaccines and healthcare.[1, 2, 3]

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

Treatment options for COVID-19

Treatment Who Route Duration Time from Illness Onset Specific Issues
Nirmatrelvir-Ritonavir (Paxlovid) Adults; children aged 12 years and older and at least 40kg Oral 5 days ≤5 days Adjust dosing in some cases; drug-drug interactions; severe kidney and liver contraindications; no specific testing required before initiation
Remdesivir (Veklury) Adults; children aged 28 days and older and at least 3kg Intravenous 3 days ≤7 days Infusion over 30-120 minutes; infusion over 3 consecutive days; need to check liver function and prothrombin time before initiation
Recommended to use if above medications cannot be used or are unavailable. 
Molnupiravir (Lagrevio) Adults Oral 5 days ≤5 days Women who are able to become pregnant and their partners should use birth control; avoid in pregnant women; no specific testing required before initiation

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.[9]

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 rare.

Keep Reading: Learn more about COVID-19 Rebound

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 antiviral treatment.

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

Alternative Therapies

Molnupiravir

When ritonavir-boosted nirmatrelvir or remdesivir are not accessible or clinically appropriate, the oral antiviral molnupiravir can be used. [6, 7] Molnupiravir was shown to have low efficacy against severe outcomes in clinical trials and has little evidence of effectiveness particularly among vaccinated individuals.

Clinicians can use the link below to review details on eligibility and indication.

Convalescent Plasma

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 IDSA Guidelines on Treatment and Management of Patients with COVID-19 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]

Patient Assistance Programs

Patient assistance programs that help pay for the COVID-19 antivirals are available to people who are underinsured, uninsured, or publicly insured through Medicaid, Medicare or other programs. Manufacturer access programs such as PAXCESS (Paxlovid), including the U.S. Government Patient Assistance Program (USG PAP) operated by Pfizer, Merck Helps (Lagevrio), and Gilead Advanced Access (Veklury) are also available. A prescription is needed to enroll in these programs; therefore, patients should seek medical care as early as possible if they develop symptoms to avoid delays in starting treatment.

People who are privately insured or have Medicare part B may receive Pemgarda without cost share.

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.1

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.

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 is an IV-infusion monoclonal antibody that is authorized for pre-exposure prevention of COVID-19 for individuals (12 years of age and older weighing at least 40 kg). 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.

Healthcare providers should consult the Pemivibart EUA Fact Sheet and EUA Frequently Asked Questions for the FDA-authorized conditions under which pemivibart may be used. CDC is monitoring variants and how commonly they occur to understand if they might affect how well pemivibart works. The FDA will provide additional updates to the EUA materials, as appropriate, if new information emerges. This is the only preventative option available for COVID-19 for the immunocompromised community, as described above, at the present time.

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 vaccines. Alongside vaccination, practicing core prevention strategies like good hygiene, cleaner air measures, and staying home when sick are vital in preventing the spread of COVID-19.

Resources

Clinical guidance

Treatment tools and fact sheets

Disclaimer‎

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 U.S. Department of Health and Human Services.
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Content Source:
National Center for Immunization and Respiratory Diseases; Coronavirus and Other Respiratory Viruses Division
  1. 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.