Study design and setting
The Co-FriSero study (“Investigation of the outbreak of COVID-19 infection at the community- hospital Waltershausen-Friedrichroda and survey of seroprevalence and infection status of SARS-CoV-2 among facility staff”) is a prospective, monocentric, exploratory cohort study. This study was conducted between October 19th 2020 and November 18th 2020 at the community hospital Waltershausen-Friedrichroda in Germany. Friedrichroda is a small town with 7,115 inhabitants in the district of Gotha in the state of Thuringia, which is located in the center of Germany. The hospital with 185 beds has a regional care mission and 404 employees (as of August 16th 2021).
Research was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The study was approved by the ethical committee of the Thuringian Chamber of Physicians (approval no. 2020 − 1873). This outbreak was reported following the ORION guideline (https://www.ucl.ac.uk/amr/Reporting_Guidelines/ORION) for outbreak reporting.
Enrolment and definition of exposure risk
Inclusion criteria were that the subject was an employee of the hospital, 18 years of age or older, and willing to sign a written informed consent form. According to their profession (e.g., physician, nursing staff, reception area and administrative staff) and workplace (e.g., intensive care unit, emergency department, normal ward, administration), the employees were classified to predefined risk areas (low, medium, high) indicating the risk of a contact with a COVID-19-positive patient. Occupational groups outside these areas, such as laboratory staff who had partial contact with COVID-19-positive specimens but no patient contact, staff who was not available during the scheduled study period and the backup appointment, and staff who did not provide a blood sample, were excluded. The low-risk group included administrative staff and kitchen staff who had no patient contact. The medium-risk group included staff who were in contact with patients but did not routinely work with confirmed or suspected COVID-19 patients (e.g., operating room staff, functional areas, peripheral wards). The high-risk group included hospital staff who routinely cared for confirmed or suspected COVID-19 patients (e.g., intensive care unit, intermediate care unit, emergency department, isolation ward).
Questionnaire
Each participant was asked to fill a questionnaire. The questionnaire included questions on age, occupation, education level, exposure to COVID-19-positive patients, results of previous polymerase chain reaction (PCR) tests, and clinical symptoms such as sore throat, headache, cough, loss of taste and smell, and diarrhea. The questionnaire also included questions to assess the risk of nosocomial transmission asking about personal contact with confirmed COVID-19 patients or their environment, about compliance with hygienic measures and wearing personal protective equipment (PPE). These questions were based on the WHO "Assessment of risk factors for coronavirus disease 2019 (COVID-19) in health workers: protocol for a case-control study" (https://www.who.int/publications/i/item/assessment-of-risk-factors-for-coronavirus-disease-2019-(covid-19)-in-health-workers-protocol-for-a-case-control-study).
SARS-CoV-2 antibody testing
Primary testing for the presence of SARS-CoV-2 antibodies was performed using two different IgG detection immunoassays: chemiluminescence immunoassay technology (CLIA) LIAISON (DiaSorin) and enzyme immunoassay EDI Novel Coronavirus SARS-CoV-2 IgG ELISA (Epitope Diagnostics Inc.). Both assays target the presence of antibodies to recombinant nucleoside capsid proteins and were performed according to the manufacturer's instructions. With two matched positive test results in both immunoassays, the participant was classified as SARS-CoV-2-seropositive and with two concordant negative test results, the participant was classified as seronegative. In the event of discrepant results, a third test (recomeLine SARS-CoV-2 IgG immunoassay, microgene) was used according to the manufacturer's instructions to make a final decision. In this test, the diagnostic markers, nucleocapsid protein and spike protein are set as immunodominant antigens. For all three tests, both sensitivity and specificity were reported by the manufacturer to be high (> 98%).
Statistical methods
Characteristics of study participants (overall and stratified by SARS-CoV-2 test result) were summarized as both absolute and relative frequencies, as well as median with first and third quartiles (Q1, Q3). Logistic regression modelling according to Firth was used to investigate the association between seropositivity of study participants working in different COVID-19 risk areas and potential risk factors as well as clinical symptoms. In univariable models, we chose SARS-CoV-2 seropositivity (binary) as the dependent variable and the respective factors under investigation as independent variables. Additionally, we adjusted these models for age and sex to account for these possible confounders. To receive comparable results between an univariable and the respective multivariable model, we excluded participants without information on age and sex from the univariable models. We report (adjusted) odds ratios (OR) together with their 95% confidence intervals (CI) and p-value. Logistic regression modelling was performed with R (version 4.2.2) and the R package logistf (version 1.25.0). All remaining analyses were done with SPSS Statistics version 27.0 for Apple (IBM Corp., Armonk, NY, USA).