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- Title
SARS-CoV-2 Serosurveys: How antigen, isotype and threshold choices affect the outcome.
- Authors
Binder, Raquel A; Fujimori, Gavin F; Forconi, Catherine S; Reed, George W; Silva, Leandro S; Lakshmi, Priya Saikumar; Higgins, Amanda; Cincotta, Lindsey; Dutta, Protiva; Salive, Marie-Claire; Mangolds, Virginia; Anya, Otuwe; Calle, J Mauricio Calvo; Nixon, Thomas; Tang, Qiushi; Wessolossky, Mireya; Wang, Yang; Ritacco, Dominic A; Bly, Courtney S; Fischinger, Stephanie
- Abstract
<bold>Background: </bold>Evaluating the performance of SARS-CoV-2 serological assays and clearly articulating the utility of selected antigen, isotypes and thresholds is crucial to understanding the prevalence of infection within selected communities.<bold>Methods: </bold>This cross-sectional study, implemented in 2020, screened PCR-confirmed COVID-19 patients (n = 86), banked pre-pandemic and negative donors (n = 96), health care workers and family members (n = 552), and university employees (n = 327) for anti-SARS-CoV-2 receptor-binding domain (RBD), trimeric spike protein (S), and nucleocapsid protein (N) IgG and IgA antibodies with a laboratory developed Enzyme-Linked Immunosorbent Assay (ELISA) and tested how antigen, isotype and threshold choices affected the seroprevalence. The following threshold methods were evaluated: (i) mean + 3 standard deviations of the negative controls; (ii) 100% specificity for each antigen/isotype combination; and (iii) the maximal Youden index.<bold>Results: </bold>We found vastly different seroprevalence estimates depending on selected antigens, isotypes and the applied threshold method, ranging from 0.0% to 85.4% . Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3% to 25.9%.<bold>Conclusions: </bold>This study revealed the importance of evaluating serosurvey tools for antigen, isotype, and threshold-specific sensitivity and specificity, in order to interpret qualitative serosurvey outcomes reliably and consistently across studies.
- Subjects
MASSACHUSETTS; SARS-CoV-2; COVID-19
- Publication
Journal of Infectious Diseases, 2023, Vol 227, Issue 3, p371
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiac431