Retrospective, Observational Studies for Estimating Vaccine Effects on the Secondary Attack Rate of SARS-CoV-2

Abstract

Coronavirus disease 2019 (COVID-19) vaccines are highly efficacious at preventing symptomatic infection, severe disease, and death. Most of the evidence that COVID-19 vaccines also reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is based on retrospective, observational studies. Specifically, an increasing number of studies are evaluating vaccine effectiveness against the secondary attack rate of SARS-CoV-2 using data available in existing health-care databases or contact-tracing databases. Since these types of databases were designed for clinical diagnosis or management of COVID-19, they are limited in their ability to provide accurate information on infection, infection timing, and transmission events. We highlight challenges with using existing databases to identify transmission units and confirm potential SARS-CoV-2 transmission events. We discuss the impact of common diagnostic testing strategies, including event-prompted and infrequent testing, and illustrate their potential biases in estimating vaccine effectiveness against the secondary attack rate of SARS-CoV-2. We articulate the need for prospective observational studies of vaccine effectiveness against the SARS-CoV-2 secondary attack rate, and we provide design and reporting considerations for studies using retrospective databases.

Keywords: COVID-19; SARS-CoV-2; retrospective studies.

Figure 1

Analytical comparison of actual (y-axis) and target (x-axis) vaccine efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission estimands. The dashed line indicates equality. A) Difference between target and actual estimands under symptom-prompted testing under varying reduction in transmission potential for asymptomatic versus symptomatic infections. B) Difference between target and actual estimands under infrequent testing under varied frequency of testing. Note the different scales of the 2 x- and y-axes. In (A), the color indicates percent reduction in the secondary attack rate comparing asymptomatic to symptomatic infected people: A value of 100% indicates that asymptomatic infected people cannot transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a value of 0% indicates that the transmission potential for asymptomatic and symptomatic people is the same. In (B), the color indicates interval between subsequent tests (e.g., a value of 7 means that individuals were tested once every 7 days). “Actual” estimand refers to the estimand that is available given the sampling design, and is derived analytically (see Web Material).

Figure 2

True and inferred transmission chains for 2 hypothetical transmission units, each with 1 primary case and 3 susceptible contacts. Black dots represent true or inferred transmission events. A) True infection and transmission histories. B) Inferred transmission events based on symptom-prompted testing. C) Inferred transmission events based on infrequent testing. D) Inferred transmission events if community acquisition events are incorrectly included as transmission events. E) Inferred transmission events if contact-to-contact transmissions are incorrectly included as transmission events.