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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Adis, Springer Healthcare 2020-09-01
• Series: Infectious Diseases and Therapy
• Subjects: Coronavirus; COVID-19; Healthcare professionals; Humoral immunity; Infection; Pandemic
• Online Access: https://doi.org/10.1007/s40121-020-00334-1
• ISSN: 2193-8229; 2193-6382

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.