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SARS-CoV-2 Serosurveys: How antigen, isotype and threshold choices affect the outcome.
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; Atyeo, Caroline; Oluoch, Peter O; Odwar, Boaz; Bailey, Jeffrey A; Maldonado-Contreras, Ana; Haran, John P; Schmidt, Aaron G; Cavacini, Lisa; Alter, Galit; Moormann, Ann M.
  • Binder RA; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Fujimori GF; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Forconi CS; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Reed GW; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Silva LS; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Lakshmi PS; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Higgins A; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Cincotta L; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Dutta P; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Salive MC; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Mangolds V; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Anya O; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Calle JMC; Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Nixon T; Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Tang Q; Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Wessolossky M; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Wang Y; MassBiologics of the University of Massachusetts Chan Medical School, Boston, MA, USA.
  • Ritacco DA; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Bly CS; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Fischinger S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Atyeo C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Oluoch PO; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Odwar B; Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Bailey JA; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA.
  • Maldonado-Contreras A; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Haran JP; Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Schmidt AG; Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Cavacini L; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
  • Alter G; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
  • Moormann AM; MassBiologics of the University of Massachusetts Chan Medical School, Boston, MA, USA.
J Infect Dis ; 2022 Oct 31.
Article in English | MEDLINE | ID: covidwho-2228160
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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%.

CONCLUSIONS:

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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study / Experimental Studies / Observational study / Prognostic study / Qualitative research / Randomized controlled trials Language: English Year: 2022 Document Type: Article Affiliation country: Infdis

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study / Experimental Studies / Observational study / Prognostic study / Qualitative research / Randomized controlled trials Language: English Year: 2022 Document Type: Article Affiliation country: Infdis