Effectiveness of COVID-19 Vaccines: A Vaccinated-Only Approach

We used a modified screening method that ensures quasi-exchangeability of comparison groups to estimate COVID-19 vaccine effectiveness in people resident in the Federal State of Hessen, Germany. COVID-19 vaccination history of vaccinated subjects with reported symptomatic SARS-CoV-2 infection was used to determine vaccination status. Subjects with their first COVID-19 vaccination within 7 days before the imputed date of infection were considered unvaccinated. Vaccination is assumed not to have a relevant effect on outcome risk for the first seven days and to be fully developed after between 14 and 21 days. The immunization profile of the source population was estimated from the number of subjects vaccinated by dose, date and age group as recorded in the Hessian COVID-19 vaccination registry. Effect estimates were obtained using logistic regression, fitted by a Bayesian approach. The first dose of COVID-19 vaccines had a measurable effect during the predominance of the Alpha and Delta variants of SARS-CoV-2, but a smaller effect during Omicron predominance. Only during Alpha and Delta predominance did the second dose provide an added benefit. During Omicron predominance, the third dose provided additional protection, but that effect was smaller than for the Delta period. Comparison of our estimates with estimates using a conventional, not quasi-exchangeable, approach revealed substantial differences in some cases, without any recognizable pattern. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in the present study are available in aggregated form upon reasonable request to the authors