Antibody tests for identification of current and past infection with SARS-CoV-2

Abstract

Background The diagnostic challenges associated with the COVID‐19 pandemic resulted in rapid development of diagnostic test methods for detecting SARS‐CoV‐2 infection. Serology tests to detect the presence of antibodies to SARS‐CoV‐2 enable detection of past infection and may detect cases of SARS‐CoV‐2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARS‐CoV‐2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARS‐CoV‐2 epidemiology. Objectives To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARS‐CoV‐2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARS‐CoV‐2. Sources of heterogeneity investigated included: timing of test, test method, SARS‐CoV‐2 antigen used, test brand, and reference standard for non‐SARS‐CoV‐2 cases. Search methods The COVID‐19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Co‐ordinating Centre (EPPI‐Centre) ‘COVID‐19: Living map of the evidence’ and the Norwegian Institute of Public Health ’NIPH systematic and living map on COVID‐19 evidence’. We did not apply language restrictions. Selection criteria We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RT‐PCR test. Small studies with fewer than 25 SARS‐CoV‐2 infection cases were excluded. We included any reference standard to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction tests (RT‐PCR), clinical diagnostic criteria, and pre‐pandemic samples). Data collection and analysis We use standard screening procedures with three reviewers. Quality assessment (using the QUADAS‐2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for meta‐analysis, we fitted univariate random‐effects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the random‐effects logistic regression models. We tabulated result...

Performance of an interferon-γ release assay-based test for cell-mediated immunity to SARS-CoV-2

“…CMI NC testing exhibited performance characteristics with almost comparative features as a commercially available anti-NC antibody-based diagnostic test. In contrast to serologic assays which apparently exhibit comparable performance independent from antibody specificity to S or NC ( 29 ), the use of S peptides for CMI led to inferior specificity for detection of SARS-CoV-2 infection. Apparently, in a recent study dominant immunogenic HLA-DR SARS-CoV-2 T cell epitopes were mainly found to be derived from the NC protein ( 30 ).…”

Are anti-SARS-CoV-2 S/N IgG/IgM antibodies always predictive of previous SARS-CoV-2 infection?

“…The generation of N (nucleocapsid)-specific antibodies, especially those belonging to the IgG class, is characteristic of patients in the convalescent phase of acute SARS-CoV-2 infection. The comprehensive analysis published by the Cochrane COVID-19 Diagnostic Test Accuracy Group has emphasized that anti-SARS-CoV-2 IgG antibodies develop in as many as 90% of all subjects recovering from an acute infection, while anti-SARS-CoV-2 IgM antibodies develop with a substantially lower frequency (i.e., around 70%) [4]. Thus, anti-SARS-CoV-2 IgG antibodies seem a globally more robust and reliable measure of acquired SARS-CoV-2 immunity than anti-SARS-CoV-2 N IgM antibodies.…”

“…The assessment of anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus disease 2) antibodies is widely used as a surrogate measure of molecular test positivity for identifying previous SARS-CoV-2 infections across many different settings [1]. In particular, the quantification of anti-SARS-CoV-2 antibodies directed against the nucleocapsid protein (N) rather than versus the spike (S) protein of the virus has been employed in many serological surveys in regions where coronavirus disease 2019 (COVID-19) vaccination is conducted with vaccines not containing the sequence (or part of) of the N protein, since the identification of anti-SARS-CoV-2 N antibodies would thus enable to identify the presence of an immune response against the virus and thus, theoretically, to classify the subjects as "infected" or "previously infected" by SARS-CoV-2 [2][3][4].…”

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months

“…Here, self-reports were used to detect possible reinfections, since all the cases we recruited as incident cases. Others have used varied methods to differentiate reinfection from initial infection ( 40 , 41 ). One macaque study showed a 7.6-fold rise in N-IgG antibody as indicative of reinfection ( 21 ), while a human West Africa study suggested a 7-fold rise ( 20 ); similar titre rises were also observed in studies from high-income settings ( 42 , 43 ).…”