Infectious Diseases and Therapy (Sep 2020)

Strategic Anti-SARS-CoV-2 Serology Testing in a Low Prevalence Setting: The COVID-19 Contact (CoCo) Study in Healthcare Professionals

  • Georg M. N. Behrens,
  • Anne Cossmann,
  • Metodi V. Stankov,
  • Bianca Schulte,
  • Hendrik Streeck,
  • Reinhold Förster,
  • Berislav Bosnjak,
  • Stefanie Willenzon,
  • Anna-Lena Boeck,
  • Anh Thu Tran,
  • Thea Thiele,
  • Theresa Graalmann,
  • Moritz Z. Kayser,
  • Anna Zychlinsky Scharff,
  • Christian Dopfer,
  • Alexander Horke,
  • Isabell Pink,
  • Torsten Witte,
  • Martin Wetzke,
  • Diana Ernst,
  • Alexandra Jablonka,
  • Christine Happle

DOI
https://doi.org/10.1007/s40121-020-00334-1
Journal volume & issue
Vol. 9, no. 4
pp. 837 – 849

Abstract

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Abstract Background Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. Methods In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2. Results From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6, p < 0.001). In sera of convalescent patients with PCR-confirmed COVID-19, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from enzyme-linked immunosorbent assays (ELISA) using e.g. the spike 1 (S1) protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralisation. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the study period of 6 weeks. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralisation against live SARS-CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%. Conclusion When assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates. Trial Registration The study is registered at DRKS00021152.

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