Nirmatrelvir-Ritonavir Highly Effective at Preventing COVID-19 Hospitalization, RWE Says

The study of real-world evidence (RWE) found nearly 9 in 10 patients in a highly vaccinated cohort avoided hospitalization within 15 days of treatment for COVID-19.

Early treatment for COVID-19 with oral Paxlovid (nirmatrelvir-ritonavir) appears to be highly effective at preventing hospitalization, according to a newly released report based on real-world data from more than 25,000 patients published on MedRxiv.

The study investigators said numerous efforts have been made since the onset of the COVID-19 pandemic to reduce the risk of severe disease in patients who become infected. Strategies include dispensing neutralizing monoclonal antibody therapies and the antiviral agent remdesivir (Veklury).

“However, the need to deliver these treatments by intravenous infusion has limited their utility for broad implementation in ambulatory care settings,” the authors noted.

Nirmatrelvir-ritonavir was also found in a study to reduce the risk of severe disease in high-risk, unvaccinated adults, prompting the FDA to grant an emergency use authorization for the therapy to treat high-risk people with COVDI-19 over the age of 12. However, the researchers said there has yet to be a large-scale study looking at real-world evidence of nirmatrelvir-ritonavir’s performance in limiting COVID-19–related hospitalizations.

They decided to examine real-world data from Kaiser Permanente’s Southern California health care system to see how the experiences of patients differed when they received nirmatrelvir-ritonavir 0 to 5 days after symptom onset. The authors built a cohort of 4329 patients who received nirmatrelvir-ritonavir and 20,980 matched controls who did not receive the oral therapy. Patients were followed for at least 30 days following COVID-19 confirmation.

Most patients in the cohort were vaccinated, with 93% of the 25,039 total participants having received at least 2 doses of a SARS-CoV-2 vaccine and 78.1% having received at least 3 doses. Nearly all the patients (94.2%) were symptomatic at testing, which the authors said took place on average 2.1 days following symptom onset.

The data showed that nirmatrelvir-ritonavir was usually effective at preventing hospitalization. At 15 days, nirmatrelvir-ritonavir’s effectiveness at preventing all-cause hospitalization was 88.1% (95% CI, 49.0%-97.5%). At 30 days, it was 71.9% effective (95% CI, 25.3%-90.0%). In addition, the therapy appeared to be 88.3% effective at preventing acute respiratory infection–related hospitalizations at 15 days (95% CI, 12.9%-98.8%) and 87.3% effective at 30 days (95% CI, 18.3%-98.5%). Similar numbers were reported when the authors expanded their analysis to include people who received nirmatrelvir-ritonavir at any point (including after 5 days following symptom onset).

The investigators said the modest waning of hospitalization prevention over 30 days is likely due to hospitalizations that were not related to COVID-19, while hospitalizations within the first 15 days were more likely to be linked with acute respiratory infection.

The authors noted that although the study that led to FDA authorization was undertaken when the Delta variant of SARS-CoV-2 was most prevalent, their data were from the first 7 months of 2022, when the Omicron variant was dominant. That suggests the therapy works even with never variants.

“These findings confirm the added value of nirmatrelvir-ritonavir in preventing severe clinical outcomes, despite the potential risk of prolonged viral shedding after treatment, in populations with high levels of immunity derived either from vaccination or prior natural infection,” the authors concluded.


Lewnard JA, Malden D, Hong V, et al. Effectiveness of nirmatrelvir-ritonavir against hospital admission: a matched cohort study in a large US healthcare system. Preprint. medRxiv. 2022;2022.10.02.22280623. Published 2022 Oct 4. doi:10.1101/2022.10.02.22280623

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