This is an official

CDC Health Advisory

COVID-19 Rebound After Paxlovid Treatment

Summary

Background

• Test positive for SARS-CoV-2 infection;
• Have mild to moderate illness;
• Have one or more risk factors for progression to severe disease;
• Do not require hospitalization due to severe or critical COVID-19 at the time of treatment initiation; and
• Do not have evidence of severe renal or hepatic impairment.

Recommendations for Healthcare Providers

• There is currently no evidence that additional treatment for COVID-19 is needed for COVID-19 rebound. Based on data available at this time, patient monitoring continues to be the most appropriate management for patients with recurrence of symptoms after completion of a treatment course of Paxlovid.
• Advise people with COVID-19 rebound to follow CDC’s guidance on isolation and take precautions to prevent further transmission. Patients should re-isolate for at least 5 days. Per CDC guidance, they can end their re-isolation period after 5 full days if fever has resolved for 24 hours (without the use of fever-reducing medication) and symptoms are improving. The patient should wear a mask for a total of 10 days after rebound symptoms started.
• Consider clinical evaluation of patients who have COVID-19 rebound and symptoms that persist or worsen.
• Healthcare providers are encouraged to report cases of COVID-19 rebound to Pfizer after Paxlovid treatment using the following online tool: Pfizer Safety Reporting and to FDA MedWatch. Complete and submit a MedWatch form, or complete and submit FDA Form 3500 (health professional) by fax (1-800-FDA-0178). Call 1-800-FDA-1088 for questions.

• Healthcare providers should counsel patients on available COVID-19 treatment options, particularly for those patients at increased risk of developing severe COVID-19.
• Paxlovid should be considered for any patient who meets the eligibility criteria. For information on Paxlovid eligibility, refer to FDA’s Fact Sheet for Healthcare Providers.
• Due to the potential for severe drug-drug interactions with the ritonavir component of Paxlovid, it is strongly suggested that healthcare providers not experienced in prescribing this drug refer to the Fact Sheet for Healthcare Providers, the Paxlovid Patient Eligibility Screening Checklist Tool for Prescribers, and the NIH Statement on Paxlovid Drug-Drug Interactions | COVID-19 Treatment Guidelines. Healthcare providers can also contact a local clinical pharmacist or infectious disease specialist for advice.
• For further information on the use of Paxlovid, CDC recommends healthcare providers continue to closely follow NIH’s COVID-19 Treatment Guidelines, the Assistant Secretary for Preparedness and Response Public Health Emergency COVID-19 Therapeutics site, and IDSA’s Guidelines on the Management of Patients with COVID-19.

Recommendations for Public Health Departments and Public Health Jurisdictions

• State and local health departments should be aware of COVID-19 rebound and disseminate the recommendations for healthcare providers and the public.
• Health departments should communicate to individuals about measures to prevent further transmission. The phenomenon of COVID-19 rebound reiterates the importance of following CDC’s isolation guidance. Isolation should be restarted after the onset of rebound symptoms or a positive test result. Per CDC guidance, people can end re-isolation after 5 full days with resolution of their fever for 24 hours (without the use of fever-reducing medication) and if their symptoms are improving. The individual should wear a mask for a total of 10 days after rebound symptoms started.
• Health departments should communicate ongoing and up to date information on therapeutics for COVID-19 and their availability to healthcare providers within their jurisdiction.

Recommendations for the Public

• You may be experiencing COVID-19 rebound if you have been diagnosed in the past 2 weeks and have recovered from COVID-19 and then experience recurrent COVID-19 symptoms or develop newly positive test results after recovery.
• If you experience COVID-19 rebound, you should follow CDC’s isolation guidance. Isolate again and restart the recommended 5-day isolation period at the time of recurrence of symptoms or a new positive COVID-19 test result. You can end re-isolation after 5 days if you are fever-free for 24 hours without the use of fever-reducing medication and your symptoms are improving. You should also wear a mask for 10 days after rebound.
• Contact a healthcare provider if your COVID-19 rebound symptoms persist or worsen.
• Consult with your healthcare provider if you have additional questions about your treatment.
• You are encouraged to report a possible case of COVID-19 rebound after Paxlovid treatment to Pfizer using the following online tool: Pfizer Safety Reporting.

For More Information

• FDA Updates on Paxlovid for Health Care Providers | FDA
• Paxlovid Patient Eligibility Screening Checklist Tool
• FDA Paxlovid Emergency Use Authorization letter
• COVID-19 Treatment Guidelines: What’s New
• COVID-19 Treatment Guidelines: Antiviral Therapy
• NIH Statement on Therapies for High-Risk, Nonhospitalized Patients | COVID-19 Treatment Guidelines
• NIH Statement on Paxlovid Drug-Drug Interactions | COVID-19 Treatment Guidelines
• Pfizer Safety Reporting

References

1. 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. New Engl J Med 2022; 386(15): 1397-1408.
2. Gupta K, Strymish J, Stack G, Charness M. Rapid relapse of symptomatic omicron SARS CoV-2 infection following early suppression with nirmatrelvir/ritonavir. 26 April 2022, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1588371/v1].
3. Charness M, Gupta K, Stack G, Strymish J, Adams E, Lindy D, Mohi H, Ho D. Rapid relapse of symptomatic omicron SARS CoV-2 infection following early suppression with nirmatrelvir/ritonavir. 13 May 2022, PREPRINT (Version 2) available at Research Square [https://doi.org/10.21203/rs.3.rs-1588371/v2].
4. Carlin AF, Clark AE, Chaillon A, Garretson AF, Bray W, Porrachi M, et al. Virologic and Immunologic Characterization of COVID-19 Recrudescence after Nirmatrelvir/Ritonavir Treatment. 18 May 2022, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1662783/v1].
5. Food and Drug Administration. FDA Updates on Paxlovid for Health Care Providers. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-updates-paxlovid-health-care-providers. Accessed on May 12, 2022. Categories