COVID-19 vaccination effectiveness rates by week and sources of bias (preprint)

ABSTRACT

Importance Randomized clinical trials and observational studies have demonstrated high overall effectiveness for the three US-authorized COVID-19 vaccines against symptomatic COVID-19 infection. Nevertheless, the challenges associated with the use of observational data can undermine the results of the studies. Objective To assess the feasibility of using observational data for vaccine effectiveness studies by examining granular weekly effectiveness. Design, Settings and Participants In this retrospective cohort study, we used Columbia University Medical Center data linked to State and City Immunization Registries to assess the weekly effectiveness of mRNA COVID-19 vaccines. We conducted manual chart review of cases in week one in both groups along with a set of sensitivity analyses for Pfizer- BioNTech, Moderna and Janssen vaccines. Main Outcomes and Measures We used propensity score matching with up to 54,987 covariates and fitted Cox proportional hazards models to estimate hazard ratios and constructed Kaplan-Meier plots for two main outcomes (COVID-19 infection and COVID-19-associated hospitalization). Results The study included 179,666 patients. We observed increasing effectiveness after the first dose of mRNA vaccines with week 6 effectiveness approximating 84% (95% CI 72-91%) for COVID-19 infection and 86% (95% CI 69-95) for COVID-19-associated hospitalization. When analyzing unexpectedly high effectiveness in week one, chart review revealed that vaccinated patients are less likely to seek care after vaccination and are more likely to be diagnosed with COVID-19 during the encounters for other conditions. Sensitivity analyses showed potential outcome misclassification for COVID-19 ICD10-CM diagnosis and the influence of excluding patients with prior COVID-19 infection and anchoring in the unexposed group. Overall vaccine effectiveness analysis in fully vaccinated patients matched the results of the randomized trials. Conclusions and Relevance Observational data can be used to ascertain vaccine effectiveness if potential biases are accounted for. The data need to be scrutinized to ensure that compared groups exhibit similar health seeking behavior and are equally likely to be captured in the data. Given the difference in temporal trends of vaccine exposure and baseline characteristics, indirect comparison of vaccines may produce biased results.