Association of COVID-19 Vaccination with Risk of Medically-Attended Post-Acute Sequelae of COVID-19 During the Ancestral, Alpha, Delta, and Omicron Variant Eras

Abstract

Structured Abstract Background Uncertainty exists regarding the effectiveness of COVID-19 vaccine to prevent Post-Acute Sequelae of COVID-19 (PASC) following a breakthrough infection. While most studies using symptom surveys found an association between preinfection vaccination status and PASC symptoms, studies of medically attended PASC are less common and have reported conflicting findings. Methods In this retrospective cohort of patients with an initial SARS-CoV-2 infection, who were continually empaneled for primary care in a large US health system, the electronic health record was queried for pre-infection vaccination status, demographics, comorbidity index, and diagnosed conditions. Multivariable logistic regression was used to model the outcome of a medically-attended PASC diagnosis within 6 months of SARS-CoV-2 infection. Likelihood ratio tests were used to assess the interaction between vaccination status and prevalent variant at the time of infection, and between vaccination status and hospitalization for the SARS-CoV-2 infection. Results During the observation period, 6.9% of patients experienced medically-attended and diagnosed PASC. A diagnosis of PASC was associated with older age, female sex, hospitalization for the initial infection, and an increased severity-weighted comorbidity index, and was inversely associated with infection during the Omicron period. No difference in the development of diagnosed PASC was observed between unvaccinated patients, those vaccinated with 2 doses of an mRNA vaccine, and those with >2 doses. Conclusions We found no association between vaccination status at time of infection and subsequent development of medically diagnosed PASC. Vaccine remains an important measure to prevent SARS-CoV-2 infection and severity. Further research is needed to identify effective measures to prevent and treat PASC.