Nirmatrelvir/ritonavir treatment and risk for postacute sequelae of COVID-19 in older Singaporeans

Objectives: Significant heterogeneity has been reported in cohort studies evaluating the impact of early oral antiviral treatment on preventing postacute sequelae after COVID-19. We evaluated the impact of early nirmatrelvir/ritonavir on risk of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses, as well as postacute symptoms amongst older Singaporeans.

Methods: National COVID-19 registries and healthcare claims databases were used to construct a retrospective population-based cohort enrolling all Singaporeans aged ≥60 years diagnosed with SARS-CoV-2 infection in primary care during Omicron transmission (18 March 2022-4 August 2023). The cohort was divided into nirmatrelvir/ritonavir-treated and untreated groups. Between-group differences in baseline characteristics were adjusted using overlap weighting. Risks of postacute cardiovascular, neurological, respiratory, and autoimmune diagnoses and postacute symptoms (31-180 days) after SARS-CoV-2 infection were contrasted in treated/untreated groups using competing risks regressions (adjusted for demographics/vaccination status/comorbidities).

Results: A total of 188 532 older Singaporeans were included; 5.8% (10 905/188 532) received nirmatrelvir/ritonavir. No significantly decreased risk of postacute sequelae (any sequelae: adjusted hazards ratio [aHR], 1.06; 0.94-1.19; cardiovascular sequelae: aHR, 1.01; 0.83-1.24; neurological sequelae: aHR, 1.09; 0.95-1.27; respiratory sequelae: aHR, 1.14; 0.84-1.55; autoimmune sequelae: aHR, 0.76; 0.53-1.09; or any postacute symptom: aHR, 0.97; 0.80-1.18) was observed up to 180 days post-infection in nirmatrelvir/ritonavir-treated individuals vs. untreated cases. Across all vaccination and age subgroups, no significantly decreased risk of any postacute diagnosis/symptom or any cardiovascular, neurological, respiratory, and autoimmune complications up to 180 days post-infection was observed.

Discussion: Early outpatient receipt of nirmatrelvir/ritonavir did not significantly reduce risk of postacute cardiovascular, neurological, respiratory, and autoimmune sequelae or the risk of postacute symptoms in a boosted cohort of older Singaporeans.