Serological assays for delayed SARS-CoV-2 case identification
Authors: Kay Weng Choy
Journal: The Lancet Respiratory Medicine (2020)

In their Article, published in The Lancet Respiratory Medicine in July, 2020, on point-of-care serological assays for delayed severe acute respiratory coronavirus 2 (SARS-CoV-2) case identification among health-care workers in the UK, Pallett and colleagues1Pallett SJC Rayment M Patel A et al.Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK; a prospective multicenter cohort study.Lancet Respir Med. 2020; 8: 885-894Summary Full Text Full Text PDF PubMed Scopus (84) Google Scholar evaluated two lateral flow serological assays. The authors included sera positive for IgM or IgG antibodies against some infectious conditions in the assay specificity studies; however, they have not assessed the potential for assay cross-reactivity with autoantibodies present in the sera of patients with autoimmune disease.2Wang Y Sun S Shen H et al.Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases.Cell Mol Immunol. 2004; 1: 304-307PubMed Google Scholar Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases was previously reported.2Wang Y Sun S Shen H et al.Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases.Cell Mol Immunol. 2004; 1: 304-307PubMed Google Scholar Immunodeficiency can lead to false negative serology results; therefore, the measurements of total immunoglobulins (such as total IgG) should be considered, along with any patient history of immunodeficiency.3Goetz L Yang J Green W Zhu Y A COVID-19 patient with repeatedly undetectable SARS-CoV-2 antibodies.J Appl Lab Med. 2020; (published online Aug 3.)https://doi.org/10.1093/jalm/jfaa137Crossref PubMed Scopus (11) Google Scholar Along with serum samples, evaluation using whole blood samples on the lateral flow serological assays should be done because a whole blood sample is likely to be the primary sample type at point-of-care. Immune responses might differ with age (hence the proportion of patients who develop IgG antibodies and their IgG persistence could differ with age), an investigation of age differences in the development of SARS-CoV-2 IgG antibodies in the study cohort might be worthwhile.4Mahase E Covid-19: two antibody tests are "highly specific" but vary in sensitivity, evaluations find.BMJ. 2020; (published online May 21.)https://doi.org/10.1136/bmj.m2066Google Scholar It is unclear if repeat serum samples per study participant were used in the study; this information is useful to determine how many participants who were serologically positive for SARS-CoV-2 contributed to the evaluation of sensitivity.4Mahase E Covid-19: two antibody tests are "highly specific" but vary in sensitivity, evaluations find.BMJ. 2020; (published online May 21.)https://doi.org/10.1136/bmj.m2066Google Scholar To improve the positive predictive value in SARS-CoV-2 testing, an orthogonal testing algorithm that directs a second test to individuals who initially test positive can be considered.5Centers for Disease Control and PreventionInterim guidelines for COVID-19 antibody testing.https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.htmlDate accessed: August 20, 2020Google Scholar Effective orthogonal algorithms are generally based on testing a patient sample with two tests, each with unique assay design characteristics, such as antigens or assay formats.5Centers for Disease Control and PreventionInterim guidelines for COVID-19 antibody testing.https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antibody-tests-guidelines.htmlDate accessed: August 20, 2020Google Scholar I declare no competing interests. Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort studyAlthough a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. Full-Text PDF Serological assays for delayed SARS-CoV-2 case identification – Author's replyWe read with interest the insightful comments put forward by Kay Weng Choy, raising important considerations for clinicians planning to use point-of-care serological assays for delayed case identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in response to those presented in our Article.1 Full-Text PDF