What is already known about this topic? Recurrence of COVID-19 symptoms and positive SARS-CoV-2 test results have been reported after completion of Paxlovid oral antiviral treatment for COVID-19, but real-world evidence of severe illness following Paxlovid is lacking.

What is added by this report? COVID-19–related hospital admissions and emergency department (ED) encounters occurring 5–15 days after Paxlovid treatment were described using data from a large integrated health care system. Reports of such hospitalizations or ED encounters occurred infrequently, representing <1% of Paxlovid-treated patients over the study period.

What are the implications for public health practice? When administered as an early-stage treatment, Paxlovid might prevent COVID-19–related hospitalization among persons with mild-to-moderate COVID-19 who are at risk for progression to severe disease.

Nirmatrelvir/ritonavir (Paxlovid) is a combination protease inhibitor that blocks replication of SARS-CoV-2 (the Virus that causes COVID-19) and has been shown to reduce the risk for hospitalization and death among patients with mild to moderate COVID-19 who are at risk for progression to severe disease* (1). In December 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for early treatment with Paxlovid among persons with mild to moderate cases of COVID-19 who are at high risk for progression to severe disease (2). FDA and a small number of published case reports have documented recurrence of COVID-19 symptoms or a positive viral test result (COVID-19 rebound) 2–8 days after recovery or a negative SARS-CoV-2 test result among patients treated with Paxlovid (3–7); however, large-scale studies investigating severe illness after Paxlovid treatment are limited. This study used electronic health record (EHR) data from a large integrated health care system in California (Kaiser Permanente Southern California [KPSC]) to describe hospital admissions and emergency department (ED) encounters related to SARS-CoV-2 infections during the 5–15 days after pharmacy dispensation of a 5-day treatment course of Paxlovid. Among 5,287 persons aged ≥12 years who received Paxlovid during December 31, 2021–May 26, 2022, 73% had received ≥3 doses of COVID-19 vaccine†, and 8% were unvaccinated. During the 5–15 days after Paxlovid treatment was dispensed, six hospitalizations and 39 ED encounters considered to be related to SARS-CoV-2 infection were identified, representing <1% of all patients to whom Paxlovid treatment was dispensed during the study period. Among these 45 persons, 21 (47%) were aged ≥65 years, and 35 (78%) had at least one underlying medical condition§ (8). This study found that hospitalization or ED encounters for COVID-19 during the 5–15 days after Paxlovid treatment was dispensed for mild to moderate COVID-19 illness were rarely identified. When administered as an early-stage treatment, Paxlovid might prevent COVID-19–related hospitalization among persons with mild to moderate cases of COVID-19 who are at risk for progression to severe disease.

Suggested citation for this article: Malden DE, Hong V, Lewin BJ, et al. Hospitalization and Emergency Department Encounters for COVID-19 After Paxlovid Treatment — California, December 2021–May 2022. MMWR Morb Mortal Wkly Rep. ePub: 21 June 2022

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