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Effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and deaths in people with COVID-19: a cohort study in a large US health-care system

Joseph A Lewnard, John M McLaughlin, Debbie Malden, et al

Lancet Infect Dis Open Access Published:March 15, 2023

DOI:https://doi.org/10.1016/S1473-3099(23)00118-4

Summary

Background

In the USA, oral nirmatrelvir–ritonavir is authorised for use in patients aged 12 years or older with mild-to-moderate COVID-19 who are at risk of progression to severe disease and hospitalisation. We aimed to establish the effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions and death in people with COVID-19 in an outpatient prescribing context in the USA.

Methods

In this matched observational outpatient cohort study in the Kaiser Permanente Southern California (CA, USA) health-care system, data were extracted from electronic health records of non-hospitalised patients aged 12 years or older who received a positive SARS-CoV-2 PCR test result (their index test) between April 8 and Oct 7, 2022, and had not received another positive test result within the preceding 90 days. We compared outcomes between people who received nirmatrelvir–ritonavir and those who did not receive nirmatrelvir–ritonavir by matching cases by date, age, sex, clinical status (including care received, the presence or absence of acute COVID-19 symptoms at testing, and time from symptom onset to testing), vaccination history, comorbidities, health-care seeking during the previous year, and BMI. Our primary endpoint was the estimated effectiveness of nirmatrelvir–ritonavir in preventing hospital admissions or death within 30 days of a positive test for SARS-CoV-2.

Findings

7274 nirmatrelvir–ritonavir recipients and 126 152 non-recipients with positive SARS-CoV-2 tests were included in our study. 5472 (75·2%) treatment recipients and 84 657 (67·1%) non-recipients were tested within 5 days of symptom onset. Nirmatrelvir–ritonavir had an overall estimated effectiveness of 53·6% (95% CI 6·6–77·0) in preventing hospital admission or death within 30 days of a positive test for SARS-CoV-2, which increased to 79·6% (33·9–93·8) when nirmatrelvir–ritonavir was dispensed within 5 days of symptom onset. Within the subgroup of patients tested within 5 days of symptom onset and whose treatment was dispensed on the day of their test, the estimated effectiveness of nirmatrelvir–ritonavir was 89·6% (50·2–97·8).

Interpretation

In a setting with high levels of COVID-19 vaccine uptake, nirmatrelvir–ritonavir effectively reduced the risk of hospital admission or death within 30 days of a positive outpatient SARS-CoV-2 test.

Funding

US Centers for Disease Control and Prevention and US National Institutes of Health.