The effect of nirmatrelvir-ritonavir on the long-term risk of neuropsychiatric sequelae following COVID-19

The retrospective cohort was conducted to assess the effect of nirmatrelvir-ritonavir (NMV-r) on the long-term risk of neuropsychiatric sequela following COVID-19. TriNetX research network was used to identify nonhospitalized adult patients who tested positive for severe acute respiratory syndrome coronavirus 2 infection or were diagnosed with COVID-19 between March 1, 2020 and July 1, 2022. Further propensity score matching method was used to create two matched cohorts with and without receiving NMV-r. The primary outcome was the incidence of neuropsychiatric sequela within a 90-day to 1-year period following a diagnosis of COVID-19. After screening 119 494 527 electronic health records, two matched cohorts of each 27 194 patients were identified. During the follow-up period, the NMV-r group demonstrated a reduced risk of any neuropsychiatric sequelae compared to the control group (odds ratio [OR], 0.634; 95% confidence interval [CI], 0.604-0.667). In comparison with the control group, the patient treated with NMV-r exhibited a markedly diminished risk of developing neurocognitive sequela (OR, 0.377; 95% CI, 0.325-0.439) and psychiatric sequela (OR, 0.629; 95% CI, 0.593-0.666). In addition, patients treated with NMV-r had a significantly reduced risk of developing dementia (OR, 0.365; 95% CI, 0.255-0.522), depression (OR, 0.555; 95% CI, 0.503-0.612), insomnia (OR, 0.582; 95% CI, 0.508-0.668) and anxiety disorder (OR, 0.645 95% CI, 0.600-0.692). Moreover, the beneficial effect of NMV-r on the neuropsychiatric sequelae was observed across further subgroup analyses. Among nonhospitalized COVID-19 patients, who at risk of disease progression, the use of NMV-r is associated with a reduction in the long-term risk of neuropsychiatric sequela, including dementia, depression, insomnia and anxiety disorder. It may be necessary to re-evaluate the use of NMV-r, as a preventive measure to reduce the risk of severe acute disease and post-acute adverse mental health outcomes.