Clinical Utility and Interpretive Guidance for SARS-CoV-2 Serological Testing

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in Wuhan, China, in 2019 and rapidly spread worldwide. Over 750 million people were infected and close to 7 million were killed from 2019 to July 2023 according to the World Health Organization. Early in the pandemic, it was suggested that serological tests can confirm atypical or remote cases and assist in clinical diagnosis when molecular testing was limited. Although clinical uses of serological testing are limited, testing remains useful to: 1) assess and differentiate vaccine from infection related immune responses (when whole cell killed vaccines are not used), 2) enable population-level vaccination/infection and/or hybrid immune response surveillance, 3) understand at the population-level how serological markers correlate with the subsequent risk of infection based on the vaccine product used and the circulating variant, and 4) understand how different types of immunosuppression or other clinical factors impact the immune response. Seroprevalence assessments for infection/vaccination and hybrid immunity was helpful to assist in early phase pandemic modeling and when integrated with vaccine status and epidemiological outcomes enabled assessment of near- and long-term vaccine efficacy. This article will provide an overview of SARS-CoV-2 immunity over time, serology testing technologies, and appropriate SARS-CoV-2 serology test utilization and interpretation.