Long COVID risk and pre-COVID vaccination in an EHR-based cohort study from the RECOVER program

Abstract

Long COVID, or complications arising from COVID-19 weeks after infection, has become a central concern for public health experts. The United States National Institutes of Health founded the RECOVER initiative to better understand long COVID. We used electronic health records available through the National COVID Cohort Collaborative to characterize the association between SARS-CoV-2 vaccination and long COVID diagnosis. Among patients with a COVID-19 infection between August 1, 2021 and January 31, 2022, we defined two cohorts using distinct definitions of long COVID-a clinical diagnosis (n = 47,404) or a previously described computational phenotype (n = 198,514)-to compare unvaccinated individuals to those with a complete vaccine series prior to infection. Evidence of long COVID was monitored through June or July of 2022, depending on patients' data availability. We found that vaccination was consistently associated with lower odds and rates of long COVID clinical diagnosis and high-confidence computationally derived diagnosis after adjusting for sex, demographics, and medical history.

Fig. 1. IPTW-adjusted Kaplan–Meier curves.

Our definition of long COVID (LC) can only be observed at least 45 days after index; time from the COVID index therefore starts at 45. Long COVID events can only be observed for the model-based outcome in 30-day increments, resulting in the observed stair-step structure. A reduced vertical axis scale is used to highlight the differentiation between the vaccinated and unvaccinated curves.

Fig. 2. Sensitivity analysis of vaccination associations.

Odds ratios (OR) are shown for logistic regression (LR), hazard ratios (HR) are shown for proportional hazards (PH). Point estimates are from models built using the full cohorts and are shown with 95% confidence intervals derived from 200 bootstrap samples. The vertical line at 1.0 represents no association. The clinic diagnosis points (n =  47,404 individuals) are using the clinic-based outcome, the long COVID (LC) model points (n =  198,514 individuals) represent different thresholds of the computational phenotype model to label LC. Higher thresholds represent higher confidence in an LC phenotype. With or without covariates refers to the presence or absence of non-vaccination predictors in the outcome models. Adjusted or unadjusted refers to the presence or absence of IPTW weighting.

Fig. 3. Cohort definition flowchart.

Cumulative number of patients meeting the study’s inclusion criteria.