Retrospective case-control study nested in a seroepidemiological investigation: multi-level assessment of risk factors for SARS-CoV-2 seroconversion among healthcare workers in a Swiss tertiary care hospital

Introduction: Healthcare workers (HCWs) are vulnerable and should be adequately protected against SARS-CoV-2. To date, we do not know the impact of specific infection control practices or exposures of HCWs on their acquisition risk of SARS-CoV-2, as tested by highly sensitive serological tests, which are already used in epidemiological studies of coronavirus acquisition and transmission. Our institution will conduct a self-funded prospective longitudinal seroprevalence survey, in order to evaluate the cumulative incidence of infection and seroconversion among HCWs, the fraction of asymptomatic infection, and estimate the level of herd immunity at the hospital level. This survey represents an ideal platform to conduct a nested epidemiologic study on HCW risk factors and exposures.Objective: To evaluate risk as well as protective factors, and compare the influence of various types of and adherence to infection control measures targeting SARS-CoV-2 on the risk of seroconversion among HCWs, controlling for the intrinsic exposure risk in different hospital working areas (high vs low risk areas).Population: Retrospective case-control study nested in a longitudinal repeated seroprevalence survey of a convenience sample of HCWs working at Geneva University Hospitals, stratified by profession and recruited in the seroprevalence survey, including nurses and physicians dedicated to areas at low risk and high-risk of exposure to SARS-CoV-2. Case will include all HCWs seropositive for IgG specific anti-SARS-CoV-2. Control will include all HCWs seronegative for IgG specific anti-SARS-CoV-2. Three controls will be selected for each case.Collected data: Individual-level data: (1) Triweekly serum samples for serological testing. (2) Questionnaire regarding demographic data, in-hospital and community exposure history, infection control practices, and symptoms suggestive for COVID-19. Aggregate-level data: (3) Infection control practices (standard precautions, contact and droplet precautions, environmental hygiene) (4) Staffing workload (nurse acuity index, occupied beds, length of stay) (5) Contamination pressure (cumulative incidence of infection by SARS-CoV-2 per unit)Statistical analysis: Factor associated with seroconversion will be analyzed a secondary mixed-effect multivariate logistic regression after pre-selection of pertinent variables using forward stepwise method and clinical pertinence. Time varying exposure will be explored in a secondary analysis comparing cases seroconverted already at baseline, and newly seroconverted cases during follow-up periods. Significance: Assessment of risk or protective factors for SARS-CoV-2 seroconversion among HCWs might help improving control of nosocomial transmission, protecting both HCWs and patients. Using a serological test will preclude the strong misclassification bias present in studies using molecular tests based on symptoms to determine cases, providing a much more complete and robust picture of the epidemiological situation. Ultimately, we aim to strengthen infection control capacity in such overwhelming viral outbreak situations.