Study demonstrates that Paxlovid protects severe COVID-19–associated outcomes among persons for whom it is recommended

In a recent Morbidity and Mortality Weekly Report (MMWR) published on the United States Center for Disease Control and Prevention (US-CDC) website, researchers assessed the association between receiving a prescription for Paxlovid and coronavirus disease 2019 (COVID-19)-related hospitalization in the ensuing 30 days.

Study: Paxlovid Associated with Decreased Hospitalization Rate Among Adults with COVID-19 — United States, April–September 2022. Image Credit: Juicy FOTO/Shutterstock


Real-world evidence on the benefit of Paxlovid, according to vaccination status, age group, and underlying health conditions, is limited. This oral antiviral medication received Emergency Use Authorization (EUA) from the Food and Drug Administration (FDA) on December 22, 2021. Since then, it has been used to treat adults with mild-to-moderate COVID-19 who are at increased risk for progression to severe illness.

About the study

In the present retrospective study, researchers analyzed records from Cosmos, a data set with electronic health records (EHR) of >160 million US citizens ≥18 years gathered by Epic, a healthcare software company. They examined the benefits of Paxlovid when given within five days of COVID-19 diagnosis in the ensuing 30 days. More specifically, the researchers used a Cox proportional hazards model to assess the association between receiving a prescription for Paxlovid and hospitalization due to COVID-19-related complications.

The study model accounted for age, gender, race/ethnicity, number of pre-existing health conditions, the region of residence and social vulnerability index, COVID-19 history and infection, and vaccination status. The team repeated the primary analyses after excluding telemedicine visits and patients hospitalized during the two days after diagnosis. It helped them assess possible bias related to symptom severity at diagnosis. The CDC reviewed the study protocol, and the study adhered to the applicable federal law and CDC policy.

Study findings

Between April 1 and August 31, 2022, the researchers identified 1,713,120 individuals ≥18 years with a COVID-19 diagnosis, of which 699,848 (40.9%) met the eligibility criteria for Paxlovid treatment, but 198,927 actually received Paxlovid within five days after diagnosis, i.e., ~28% of the eligible people. Of these 198,927 individuals, 930 sought hospital admission; however, 4,299 individuals ineligible for Paxlovid treatment were also hospitalized. Of 5,229 persons with a COVID-19 hospitalization, 3,311 (63.3%) were ≥65 years, and 930 received Paxlovid during the five days after diagnosis.

Among Paxlovid recipients, 15% had documented previous SARS-CoV-2 infection, and 68.8% had received more than two COVID-19 mRNA vaccine doses. They were also more likely to have a telehealth consult (49.1%) than nonrecipients. However, the prevalences of pre-existing health conditions were similar among Paxlovid recipients and nonrecipients, with 92.4% having at least one underlying medical condition. Around 30.2% of Paxlovid recipients were immunocompromised and accounted for 9.4% of the study population. During COVID-19-related hospitalization, 211 people died. Deaths in the Paxlovid recipient group were less compared with the nonrecipients group (0.01% vs. 0.04%).


Paxlovid is a valuable anti-SARS-CoV-2 medication because of its ease of oral administration, short therapy duration, good safety profile, and lower resistance. Though underprescribed for eligible persons with COVID-19, it protected severe COVID-19–associated complications, with more pronounced benefits among adults aged 50 to 64 and 18 to 49 years with one or more and two or more pre-existing medical conditions, respectively.

Paxlovid use decreased the overall COVID-19 hospitalization rate by 51% among those with mild-to-moderate COVID-19. Clinical trial studies have shown that Paxlovid showed an 89% reduction in severe COVID-19 outcomes among unvaccinated individuals. The current real-world study demonstrated that Paxlovid markedly diminished hospitalization risk among persons with prior infection or vaccination-induced immunity, even when Omicron subvariants are circulating in the US.

Paxlovid receipt was also associated with a lower rate of all-cause hospitalization, with an adjusted hazard ratio of 0.45. Overall, the authors emphasized using Paxlovid among eligible persons to protect against COVID-19 hospitalizations, irrespective of vaccination status, especially for older adults and those with multiple pre-existing medical conditions.