How to interpret and use COVID-19 serology and immunology tests

Background: Although molecular tests are considered the reference standard for coronavirus disease 2019 (COVID-19) diagnostics, serological and immunological tests may be useful in specific settings. Objectives: This review summarizes the underlying principles and performance of COVID-19 serological and immunological testing. Sources: Selected peer-reviewed publications on COVID-19 related serology and immunology published between December 2019 and March 2021. Content: Serological tests are highly specific but heterogeneous in their sensitivity for the diagnosis of COVID-19. For certain indications, including delayed disease presentations, serological tests can have added value. The presence of antibodies against SARS-CoV-2 may indicate a recent or past COVID-19 infection. Lateral flow immunoassay (LFIA) antibody tests have the advantages of being easy and fast to perform, but many have a low sensitivity in acute settings. Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassays (CLIAs) have higher sensitivities. Besides humoral immunity, cellular immunity is also essential for successful host defences against viruses. Enzyme-linked immunospot (ELISpot) assays can be used to measure T-cell responses against SARS-CoV-2. The presence of cross-reactive SARS-CoV-2-specific T cells in never exposed patients suggests the possibility of cellular immunity induced by other circulating coronaviruses. T-cell responses against SARS-CoV-2 have also been detected in recovered COVID-19 patients with no detectable antibodies. Implications: Serological and immunological tests are primarily applied for population-based seroprevalence studies to evaluate the effectiveness of COVID-19 control measures and increase our understanding of the immunology behind COVID-19. Combining molecular diagnostics with serological tests may optimize the detection of COVID-19. As not all infected patients will develop antibodies against SARS-CoV-2, assessment of cellular immunity may provide complementary information on whether a patient has been previously infected with COVID-19. More studies are needed to understand the correlations of these serological and immunological parameters with protective immunity, taking into account the different circulating virus variants. David S.Y. Ong, Clin Microbiol Infect 2021;27:981 (c) 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Automated summary

Molecular tests are considered the gold standard for COVID-19 diagnostics, but serological and immunological tests can also be valuable in certain situations. The presence of antibodies against SARS-CoV-2 may indicate a recent or past COVID-19 infection, and tests like ELISA and CLIA have higher sensitivities. Cellular immunity is crucial in host defences against viruses, and T-cell responses against SARS-CoV-2 can provide important information on past infections.