Coronavirus disease 2019 (COVID-19) vaccines have a critical role in preventing symptomatic illness, including serious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , and in reducing viral transmission . COVID-19 vaccines approved or authorized for emergency use in the US by the Food and Drug Administration had high efficacy against severe disease in Phase III trials, ranging from 67–95% [1, 3–5]. However, long-term management of the SARS-CoV-2 pandemic remains a substantial challenge, especially as variants of concern emerge. To inform public health policy, it is critical to monitor real-world effectiveness of COVID-19 vaccines at the population-level over longer periods of time . Numerous individual-level and environmental factors (e.g., local community transmission, social distancing and other mitigation practices, vaccine type, and vaccination coverage) impact vaccine effectiveness (VE), underscoring the importance of and need for population-based studies of VE against SARS-CoV-2 infection.
Evaluating VE is challenging given the multitude of endpoints relevant to SARS-CoV-2 infection. Many COVID-19 VE studies have evaluated severe endpoints, such as mortality and hospitalizations, often in higher risk populations. Mild and asymptomatic infections likely account for the vast majority of SARS-CoV-2 infections, with serosurveys indicating that many more infections occur than diagnosed cases . Vaccine breakthrough infections are frequently asymptomatic with one study finding that among > 10,000 breakthrough infections, over a quarter were asymptomatic . Asymptomatic individuals (including with vaccine breakthrough infections) can transmit SARS-CoV-2 to others, and thus preventing asymptomatic infection is important to decrease widespread community transmission . Therefore, VE against acquiring infection is important to assess.
Constraints on large-scale population-level monitoring of VE include the cost and logistical challenges of enrolling and following cohorts of vaccinated and unvaccinated individuals, and laboratory assays. Molecular diagnostic assays, such as reverse transcription polymerase chain reaction (rtPCR) assays applied to respiratory swab samples, are the gold standard for diagnosing SARS-CoV-2 infection. However, molecular diagnostic assays have a limited detection window, necessitating frequent follow-up that reduces the feasibility of ongoing large-scale surveillance, higher cost, and lower throughput. In contrast, serological assays that detect binding antibodies (Abs) against the Spike (S) and Nucleocapsid (NC) viral proteins are lower cost, higher throughput, and can identify SARS-CoV-2 infections after resolution.
We estimated VE using a retrospective cohort study among repeat blood donors who donated during the first half of 2021 at Vitalant, a major US blood collection organization (BCO). This proof-of-concept study demonstrates a viable approach for continued near real-time monitoring of VE via serological surveillance among repeat blood donors.