How the United States' Vaccine Adverse Event Reporting System (VAERS) Database Has Been Used to Study SARS-CoV-2 Vaccine Safety

ABSTRACT

Introduction: The rapid development and deployment of SARSCoV- 2 vaccines elevated reliance on pharmacovigilance to inform benefit-risk assessments and national vaccine policy recommendations. During the mass vaccination program against pandemic coronavirus, the VAERS received an unprecedented number of adverse event reports. The VAERS database doubled in size in 2021 and accumulated 856,340 SARS-CoV-2 vaccine reports (54.3% of all VAERS reports) as of May 6, 2022 (HHS 2022). This publicly available resource has been heavily relied upon to inform US vaccine policy. Objective(s) To understand how VAERS has been used to study the safety of the SARS-CoV-2 vaccines. Method(s) Publications containing the terms "Vaccine Adverse Event Reporting System" or VAERS and COVID-19 or SARS-CoV-2 were identified from PubMed. Non-research articles, publications that did not use VAERS or did not study SARS-CoV-2 vaccines, and withdrawn publications were excluded. Key data fields were ed from the remaining articles and summarized through descriptive statistics. Result(s) 88 publications were identified with 27 excluded upon review;1 was withdrawn, 9 were commentaries/editorials, and the remainder did not study SARS-CoV-2 vaccines in VAERS. Approximately one-half of the 61 included publications focused on one or more Adverse Events of Special Interest (e.g., anaphylaxis, facial nerve palsy, Guillain-Barre syndrome, myocarditis/pericarditis, etc.) or death rather than all events or signal detection. Several special populations were studied including children, adolescents, and "pregnant persons." Methods ranged from constructing a case series for clinical review to modeling. Adverse event reporting rates were calculated in 36 studies (58%). Denominators were derived from state or national vaccine administration data (CDC 2022), and included estimates of doses administered, number of persons vaccinated, and person-years. In more than one-third of the publications that calculated adverse event reporting rates, these values were misreported or misinterpreted by the study authors as estimates of incidence rates or cumulative incidence (risk). Conclusion(s) The rapid nationwide SARS-CoV-2 vaccine rollout resulted in an unprecedented volume of VAERS reports, which have been relied upon to investigate rare adverse events and inform vaccination policy. The methods and scientific rigor of vaccine adverse event studies varied considerably. Despite the inability to calculate incidence or risk using voluntary adverse event reports, these terms were frequently used instead of, or interchangeably with, reporting rate. Where a causal relationship exists, relying on reporting rates as a proxy for incidence may substantially distort estimates of harms (Weiss 2022).