Post-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection

Abstract

COVID-19 vaccinations protect against severe illness and death, but associations with post-COVID conditions (PCC) are less clear. We aimed to evaluate the association between prior COVID-19 vaccination and new-onset PCC among individuals with SARS-CoV-2 infection across eight large healthcare systems in the United States. This retrospective matched cohort study used electronic health records (EHR) from patients with SARS-CoV-2 positive tests during March 2021-February 2022. Vaccinated and unvaccinated COVID-19 cases were matched on location, test date, severity of acute infection, age, and sex. Vaccination status was ascertained using EHR and integrated data on externally administered vaccines. Adjusted relative risks (RRs) were obtained from Poisson regression. PCC was defined as a new diagnosis in one of 13 PCC categories 30 days to 6 months following a positive SARS-CoV-2 test. The study included 161,531 vaccinated COVID-19 cases and 161,531 matched unvaccinated cases. Compared to unvaccinated cases, vaccinated cases had a similar or lower risk of all PCC categories except mental health disorders (RR: 1.06, 95% CI: 1.02-1.10). Vaccination was associated with ≥10% lower risk of sensory (RR: 0.90, 0.86-0.95), circulatory (RR: 0.88, 0.83-0.94), blood and hematologic (RR: 0.79, 0.71-0.89), skin and subcutaneous (RR: 0.69, 0.66-0.72), and non-specific COVID-19 related disorders (RR: 0.53, 0.51-0.56). In general, associations were stronger at younger ages but mostly persisted regardless of SARS-CoV-2 variant period, receipt of ≥3 vs. 1-2 vaccine doses, or time since vaccination. Pre-infection vaccination was associated with reduced risk of several PCC outcomes and hence may decrease the long-term consequences of COVID-19.

Fig. 1. Association of prior COVID-19 vaccination and risk of PCC categories 6 months following SARS-CoV-2 infection.

Association of prior vaccination status with Post-COVID Conditions (PCC) was estimated among 161,531 vaccinated patients matched with 161,531 unvaccinated patients on Vaccine Safety Datalink site, date of SARS-CoV-2 positive test ( ± 7 days), age (exact year), sex, and severity of infection (hospital admission with COVID-19 diagnosis within 7 days of SARS-CoV-2 positive test). Relative risks (RR) and 95% confidence intervals (CI) were estimated by Poisson regression adjusted for matched variables and prior SARS-CoV-2 infection, race and ethnicity, Charlson comorbidity score, Medicaid status, influenza vaccination, and healthcare utilization in the year prior. Box sizes are inverse-variance weighted. PCC category ‘symptoms’ included headache, body ache/myalgia, fever/malaise/fatigue, lymphadenopathy, weight loss, or vertigo. To limit the impact of multiple testing, Bonferroni correction was applied to main analysis of 13 PCC categories, with 2-sided p-values at a level of significance of 0.004. *Significant with Bonferroni correction.

Fig. 2. Associations of prior COVID-19 vaccination and risk of PCC categories 6 months following SARS-CoV-2 infection, by age group.

Association of prior vaccination status with Post-COVID Conditions (PCC) was estimated among 161,531 vaccinated patients matched with 161,531 unvaccinated patients on Vaccine Safety Datalink site, date of SARS-CoV-2 positive test ( ± 7 days), age (exact year), sex, and severity of infection (hospital admission with COVID-19 diagnosis within 7 days of SARS-CoV-2 positive test). Relative risks (RR) and 95% confidence intervals (CI) were estimated by Poisson regression adjusted for matched variables and prior SARS-CoV-2 infection, race and ethnicity, Charlson comorbidity score, Medicaid status, influenza vaccination, and healthcare utilization in the year prior. PCC category ‘symptoms’ included headache, body ache/myalgia, fever/malaise/fatigue, lymphadenopathy, weight loss, or vertigo. *Associations not shown due to lack of events for PCC outcomes in the following age ranges: Endocrine and metabolic disorders among < 12 years (RR: 1.51, 95% CI: 0.30–7.61); Renal disorders among < 12 years (no estimate, due to lack of events) and 12–17 years (RR: 1.31, 95% CI: 0.06–26.71); Blood and hematologic disorders among < 12 years (no estimate, due to lack of events) and 12–17 years (RR: 0.73, 95% CI: 0.26–2.08).

Fig. 3. Associations of prior COVID-19 vaccination and risk of PCC categories 6 months following SARS-CoV-2 infection, by SARS-CoV-2 variant period*.

Association of prior vaccination status with Post-COVID Conditions (PCC) was estimated among 161,531 vaccinated patients matched with 161,531 unvaccinated patients on Vaccine Safety Datalink site, date of SARS-CoV-2 positive test ( ± 7 days), age (exact year), sex, and severity of infection (hospital admission with COVID-19 diagnosis within 7 days of SARS-CoV-2 positive test). Relative risks (RR) and 95% confidence intervals (CI) were estimated by Poisson regression adjusted for matched variables and prior SARS-CoV-2 infection, race and ethnicity, Charlson comorbidity score, Medicaid status, influenza vaccination, and healthcare utilization in the year prior. Box sizes are inverse-variance weighted. PCC category ‘symptoms’ included headache, body ache/myalgia, fever/malaise/fatigue, lymphadenopathy, weight loss, or vertigo. *Pre-Omicron: March 1st 2021 – November 30th 2021; Omicron: December 1st 2021 – February 28th 2022.