• BehrensGeorg M NGMNDepartment for Rheumatology and Clinical Immunology, Hannover Medical School, Hannover, Germany. behrens.georg@mh-hannover.de.German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Brunswick, Germany. behrens.g, 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, and Christine Happle.
• Department for Rheumatology and Clinical Immunology, Hannover Medical School, Hannover, Germany. behrens.georg@mh-hannover.de.
• Infect Dis Ther. 2020 Dec 1; 9 (4): 837-849.

BackgroundSerology 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.MethodsIn 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.ResultsFrom 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%.ConclusionWhen 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 RegistrationThe study is registered at DRKS00021152.

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