Incidence of Symptoms Associated with Post-Acute Sequelae of SARS-CoV-2 Infection In Non-Hospitalized Vaccinated Patients Receiving Nirmatrelvir-Ritonavir

Background The role of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC) is unknown. The objective of this study is to assess the effect of NMV-r in non-hospitalized, vaccinated patients on the occurrence of PASC. Methods We performed a comparative retrospective cohort study utilizing data from the TriNetX research network, including vaccinated patients ≥18 years old who subsequently developed Covid-19 between December 2021-April 2022. Cohorts were based on NMV-r administration within five days of diagnosis. Based on previously validated broad and narrow definitions, the main outcome was the presence of symptoms associated with PASC. Outcomes were assessed between 30-180 days and 90-180 days after the index Covid-19 infection. Results 1,004 patients remained in each cohort after propensity-score matching. PASC (broad definition) occurred in 425 patients (42%) in the NMV-r cohort, vs. 480 patients (48%) in the control cohort (OR 0.8 CI 0.67-0.96; p=0.01) from 30-180 days and in 273 patients (27%) in the NMV-r cohort, as compared to 347 patients (35%) in the control cohort (OR 0.707, CI 0.59-0.86; p<0.001) from 90-180 days. Narrowly defined PASC was reported in 337 (34%) patients in the NMV-r and 404 (40%) in the control cohort between 30-180 days (OR=0.75, CI 0.62-0.9, p=0.002) and in 221 (22%) in the NMV-r cohort as compared to in 278 (28%) patients in the control cohort (OR=0.7, CI 0.63-0.9, p=0.003) between 90 -180 days. Conclusions NMV-r treatment in non-hospitalized vaccinated patients with Covid-19 was associated with a reduction in the development of symptoms commonly observed with PASC and healthcare utilization. Key Points Assessment of Nirmatrelvir plus ritonavir (NMV-r) in preventing post-acute sequelae of SARS-CoV-2 infection (PASC), based on broad and narrow definitions in non-hospitalized, vaccinated patients between 30-180 days and 90-180 days. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of Lahey Hospital And Medical Center waived ethical approval for this work. The institutional review board reviewed the submission and determined that the project does not meet definitions of human subjects research according to Federal Regulations at 45 CFR 46.102(e) and/or 45 CFR 46.102(l). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon request to the authors and is also readily available at . .