A note on "Rebound" COVID-19 after nirmatrelvir-ritonavir treatment

Patients who have been treated with nirmatrelvir-ritonavir are more prone to develop "Rebound" COVID-19 symptoms within 10 days to a few weeks. This calls for close clinical judgment for clinicians to decide which patients should be treated with nirmatrelvir-ritonavir. It would be prudent to prescribe nirmatrelvir-ritonavir to patients who are highly symptomatic or at high risk for deterioration. It should not be prescribed just to decrease the duration of mild symptoms or viral shedding.

The "Rebound" phenomenon correlates with repeat higher antigen positivity, and the peak viral levels can be higher with a rebound. Irrespective of vaccination status, it can occur in both vaccinated and unvaccinated patients. Recurrent symptoms are generally mild, but severe complications may occur. A case of acute pulmonary emboli has been reported following the rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19.

Patients experiencing rebound should be isolated.

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References:

1. Ranganath N, O'Horo JC, Challener DW, et al. Rebound Phenomenon After Nirmatrelvir/Ritonavir Treatment of Coronavirus Disease 2019 (COVID-19) in High-Risk Persons. Clin Infect Dis 2023; 76:e537.

2. Anderson AS, Caubel P, Rusnak JM, EPIC-HR Trial Investigators. Nirmatrelvir-Ritonavir and Viral Load Rebound in Covid-19. N Engl J Med 2022; 387:1047.

3. Wong GL, Yip TC, Lai MS, et al. Incidence of Viral Rebound After Treatment With Nirmatrelvir-Ritonavir and Molnupiravir. JAMA Netw Open 2022; 5:e2245086.

4. Pandit JA, Radin JM, Chiang DC, et al. The Coronavirus Disease 2019 Rebound Study: A Prospective Cohort Study to Evaluate Viral and Symptom Rebound Differences in Participants Treated With Nirmatrelvir Plus Ritonavir Versus Untreated Controls. Clin Infect Dis 2023; 77:25.

5. Birabaharan M, Martin TCS. Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19. Am J Emerg Med 2022; 61:235.e5.