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Abstract Background Studies have shown that Omicron breakthrough infections can occur at higher SARS-CoV-2 antibody levels compared to previous variants. Estimating the magnitude of immunological protection induced from COVID-19 vaccination and previous infection remains important due to varying local pandemic dynamics and types of vaccination programmes, particularly among at-risk populations such as health care workers (HCWs). We analysed a follow-up SARS-CoV-2 serological survey of HCWs at a tertiary COVID-19 referral hospital in Germany following the onset of the Omicron variant. Methods The serological survey was conducted in January 2022, one year after previous surveys in 2020 and the availability of COVID-19 boosters including BNT162b2, ChAdOx1-S, and mRNA-1273. HCWs voluntarily provided blood for serology and completed a comprehensive questionnaire. SARS-CoV-2 serological analyses were performed using an Immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Antibody levels were reported according to HCW demographic and occupational characteristics, COVID-19 vaccination and SARS-CoV-2 infection history, and multivariate linear regression was used to evaluate these associations. Results In January 2022 (following the fourth COVID-19 wave in Germany including the onset of the Omicron variant), 1482/1517 (97.7%) HCWs tested SARS-CoV-2 seropositive, compared to 4.6% in December 2020 (second COVID-19 wave). Approximately 80% had received three COVID-19 vaccine doses and 15% reported a previous laboratory-confirmed SARS-CoV-2 infection. SARS-CoV-2 IgG geometric mean titres ranged from 335 (95% Confidence Intervals [CI]: 258–434) among those vaccinated twice and without previous infection to 2204 (95% CI: 1919–2531) among those vaccinated three times and with previous infection. Heterologous COVID-19 vaccination combinations including a mRNA-1273 booster were significantly associated with the highest IgG antibody levels compared to other schemes. There was an 8-to 10-fold increase in IgG antibody levels among 31 HCWs who reported a SARS-CoV-2 infection in May 2020 to January 2022 after COVID-19 booster vaccination. Conclusions Our findings demonstrate the importance of ongoing COVID-19 booster vaccination strategies in the context of variants such as Omicron and despite hybrid immunity from previous SARS-CoV-2 infections, particularly for at-risk populations such as HCWs. Where feasible, effective types of booster vaccination, such as mRNA vaccines, and the appropriate timing of administration should be carefully considered.

Abstract Background SARS-CoV-2 cases in Germany increased in early March 2020. By April 2020, cases among health care workers (HCW) were detected across departments at a tertiary care hospital in Berlin, prompting a longitudinal investigation to assess HCW SARS-CoV-2 serostatus with an improved testing strategy and associated risk factors. Methods In May/June and December 2020, HCWs voluntarily provided blood for serology and nasopharyngeal/oropharyngeal (NP/OP) samples for real-time polymerase chain reaction (PCR) and completed a questionnaire. A four-tiered SARS-CoV-2 serological testing strategy including two different enzyme-linked immunosorbent assays (ELISA) and biological neutralization test (NT) was used. ELISA-NT correlation was assessed using Pearson’s correlation coefficient. Sociodemographic and occupational factors associated with seropositivity were assessed with multivariate logistic regression. Results In May/June, 18/1477 (1.2%) HCWs were SARS-CoV-2 seropositive, followed by 56/1223 (4.6%) in December. Among those tested in both, all seropositive in May/June remained seropositive by ELISA and positive by NT after 6 months. ELISA ratios correlated well with NT titres in May/June (R = 0.79) but less so in December (R = 0.41). Those seropositive reporting a past SARS-CoV-2 positive PCR result increased from 44.4% in May/June to 85.7% in December. HCWs with higher occupational risk (based on profession and working site), nurses, males, and those self-reporting COVID-19-like symptoms had significantly higher odds of seropositivity. Conclusions This investigation provides insight into the burden of HCW infection in this local outbreak context and the antibody dynamics over time with an improved robust testing strategy. It also highlights the continued need for effective infection control measures particularly among HCWs with higher occupational risk.