Viral SARS-CoV-2 rebound rates in linked commercial pharmacy-based testing and healthcare claims

Abstract

Abstract Background Viral SARS-CoV-2 rebound (viral RNA rebound) is challenging to characterize in large cohorts due to the logistics of collecting frequent and regular diagnostic test results. Pharmacy-based testing data provides an opportunity to study the phenomenon in a large population, also enabling subgroup analyses. The current real-world evidence approach complements approaches focused on smaller, prospective study designs. Methods We linked RT-qPCR test data from national pharmacy-based testing to healthcare claims data via tokenization to calculate the cumulative incidence of viral RNA rebound within 28 days following positive test results in nirmatrelvir/ritonavir (NMV-r) treated and untreated individuals during the Omicron era (12/2021-11/2022) and prior to the Omicron era (10/2020-11/2-21). Findings Among 30,646 patients, the rate of viral RNA rebound was 3.5% (95% CI: 2.0-5.7%) in NMV-r treated infections compared to 1.5% (95% CI: 1.3-1.7%) in untreated infections during the Omicron era, and 1.9% (95% CI:1.7-2.1%) prior to the Omicron era. Viral RNA rebound in vaccinated (n=8,151), high-risk (n=4,411), or older patients (≥65yo, n=4,411) occurred at comparable rates to the overall cohort (range: 1.1-4.8%). Viral rebounds to high RNA levels in NMV-r treated infections occurred in 8% of viral rebounds, compared to 5-11% in untreated infections. Rates of hospitalization were comparable between patients with NMV-r treated infections with viral RNA rebound (0%) and untreated patients with viral RNA rebound (0-1.2%). Interpretation These findings related to viral RNA rebound are consistent with those of the EPIC-HR trial. Most occurrences of viral RNA rebound were associated with low viral RNA levels and viral RNA rebound progression to severe disease was not observed.