Waning effectiveness of mRNA COVID-19 vaccines against inpatient and emergency department encounters

In the United States, most real-world estimates of COVID-19 vaccine effectiveness are based on data drawn from large health systems or sentinel populations. More data is needed to understand how the benefits of vaccination may vary across US populations with disparate risk profiles and policy contexts. We aimed to provide estimates of mRNA COVID-19 vaccine effectiveness against moderate and severe outcomes of COVID-19 based on state population-level data sources. Using statewide integrated administrative and clinical data and a test-negative case-control study design, we assessed mRNA COVID-19 vaccine effectiveness against SARS-CoV-2-related hospitalizations and emergency department visits among adults in South Carolina. We presented estimates of vaccine effectiveness at discrete time intervals for adults who received one, two or three doses of mRNA COVID-19 vaccine compared to adults who were unvaccinated. We also evaluated changes in vaccine effectiveness over time (waning) for the overall sample and in subgroups defined by age. We showed that while two doses of mRNA COVID-19 vaccine were initially highly effective, vaccine effectiveness waned as time elapsed since the second dose. Compared to protection against hospitalizations, protection against emergency department visits was found to wane more sharply. In all cases, a third dose of mRNA COVID-19 vaccine conferred significant gains in protection relative to waning protection after two doses. Further, over more than 120 days of follow-up, the data revealed relatively limited waning of vaccine effectiveness after a third dose of mRNA COVID-19 vaccine.