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

Abstract

Background: Serology 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. Methods: In 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. Results: From 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 12.4 % 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%. 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.

Seroprevalence of anti‐SARS‐CoV‐2 antibodies in COVID‐19 patients and healthy volunteers up to 6 months post disease onset

“…We show that using only one protein for a large population screen picks up some false positives (30/2571; 1.2%). Especially when the infection rate is low, the two‐step method is highly beneficial and strongly recommended [27]. Furthermore, the introduction of an additional dilution step ensures robustness, resulting in 1.5% (38/2571) of the staff members that seroconverted.…”

“…In many countries implementing mitigation strategies, infection prevalence remained modest at the time of sampling, May–June 2020, with a low frequency of infection [26–29]. This increases the proportional contribution of any false positives to the result.…”

Half Year Longitudinal Seroprevalence of SARS-CoV-2-antibodies and Rule Compliance in German Hospital Employees

“…Behrens et al showed in their CoCo-trial a longitudinal prevalence of anti-SARS-CoV-2-IgG-antibodies of 1.86% within 6 weeks. [26] Comparing with our initial data from the initial 9 week phase of the study, we had shown a seroprevalence of 4.36% (with the limitation of different assays used in that evaluation). [20] The data presented here is comparable with the seroprevalence in the normal German population of around 0.91% between March and May 2020.…”