Strategic anti-SARS-CoV-2 serology testing in a low prevalence pandemic: The COVID-19 Contact (CoCo) Study in health care professionals (preprint)

ABSTRACT

BackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the 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-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2. ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=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{middle dot}4 % in week six, p<0.001). In sera of convalescent PCR-confirmed COVID-19 patients, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from ELISAs using e.g. the S1 spike protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralization. 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 six week study period. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralization 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.