Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus 2 : A Narrative Review

Abstract

Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.

Figure.

Possible interpretation of antibody test results, based on symptomatology. The figure shows a decision tree for interpreting antibody test results by symptomatology (symptomatic, postsymptomatic, asymptomatic or subclinical) and whether the patient is a suspected case. It is presumed herein that antibody tests with the highest possible sensitivity and specificity are used, and that the symptomatology is occurring early in the pandemic, when seroprevalence is low and before the availability of a vaccine. For SARS-CoV-2, the accuracy of antibody test results and the appropriate test interpretation both depend on clinical context. In some situations, the clinical context does not enable a single interpretation of the antibody test result. For example, a positive antibody test in a low-risk population could be the result of prior infection, or it could be a false-positive result. Similarly, a negative antibody test in a high-risk population cannot a priori differentiate among preseroconversion, undetectable seroconversion, a false-negative result, or the absence of infection. SARS-CoV-2 = severe acute respiratory syndrome–related coronavirus-2. * The relationship between positive antibody results and protective immunity will vary among assays and must be validated individually. † Includes high exposure, high risk, hot spots, and contact tracing.