Effectiveness of Nirmatrelvir/Ritonavir in Unvaccinated COVID-19 Patients Treated in the Emergency Department: A Retrospective Propensity-Matched Cohort Analysis.
Dietrich von Kuenssberg Jehle, Raheed Sunesra, Shania M Williams, Nathaniel J Bilby, Krishna K Paul, Kelcie Hill
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Abstract
Background: Nirmatrelvir/Ritonavir (nir/rit) is an antiviral combination, often sold under the brand name Paxlovid, used to treat COVID-19, particularly in high-risk individuals. Numerous COVID-19 treatments exist, but clinical studies have reported conflicting data on their efficacy, particularly in unvaccinated patients.
Objectives: This study aims to compare 28-day mortality, hospitalization, intensive care unit (ICU) admission, observation status, and hypoxia rates among unvaccinated COVID-19 patients treated with nir/rit in the emergency department (ED) versus those who did not receive nir/rit.
Design: This retrospective, propensity-matched cohort study utilized the TriNetX database, which included records of 112 million patients from 64 academic medical centers and healthcare organizations across the U.S. The study period was 2022-2024.
Methods: The treatment cohort consisted of COVID-19-unvaccinated ED patients aged 18 and above who tested positive for COVID-19 via RNA test and were administered nir/rit on the same day. Patients admitted for observation or inpatient care on the same day were excluded. Outcomes assessed within 28 days post-ED diagnosis included mortality, ICU admission, inpatient hospitalization, observation status, and hypoxia (O2 saturation ≤90%). Propensity score matching adjusted for demographics and 21 pre-existing conditions associated with COVID-19 severity and mortality.
Results: A total of 194 181 unvaccinated COVID-19 patients were identified, with 14 799 receiving nir/rit and 179 382 not receiving it. After propensity matching, 14 799 patients were included in each cohort. Paxlovid treatment was associated with lower mortality (risk ratios [RR] = 0.28, P < .001), fewer ICU admissions (RR = 0.53, P = .01), decreased inpatient visits (RR = 0.40, P < .001), reduced observation status (RR = 0.36, P = .004), and less hypoxia (RR = 0.49, P < .001). Trends were similar before propensity matching.
Conclusions: Nir/rit treatment in unvaccinated adults diagnosed with COVID-19 in the ED is associated with significantly lower mortality, ICU admissions, hospitalizations, observation status, and hypoxia, supporting its use in this patient population.
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