ABSTRACT
ABSTRACT Objectives: To assess risk factors for SARS-CoV-2 infection by first comparing positive cases with negative controls as determined by polymerase chain reaction (PCR) testing and then comparing these two groups with an additional population control group. Design and setting: Test-negative design (TND), multicentre case-control study with additional population controls in South Eastern Norway. Participants: Adults who underwent SARS-CoV-2 PCR testing between February and December 2020. PCR-positive cases, PCR-negative controls, and additional age-matched population controls. Primary outcome measures: The associations between various risk factors based on self- reported questionnaire and SARS-CoV-2 infection comparing PCR positive cases and PCR- negative controls. Using subgroup analysis, the risk factors were then compared with a population control group. Univariate and multivariate regression analyses were performed. Results: In total, 400 SARS-CoV-2 PCR-positive cases, 719 PCR-negative controls, and 14,509 population controls were included. Male sex was associated with the risk of SARS- CoV-2 infection when PCR-positive cases were compared with PCR-negative controls (OR 1.9, 95% CI 1.4 to 2.6). Age, education level, comorbidities (asthma, diabetes, hypertension), an exercise were not associated with the risk of SARS-CoV-2 infection when PCR-positive cases were compared with PCR-negative controls. In the subgroup analysis comparing PCR- positive cases with age-matched population controls, asthma was associated with the risk of SARS-CoV-2 infection (OR 1.6, 95% CI 1.1 to 2.1). Daily or occasional smoking was negatively associated with the risk of SARS-CoV-2 infection in both analyses (OR 0.5, 95% CI 0.3 to 0.8 and OR 0.55, 95% CI 0.35, to 0.82, respectively). Conclusions: Male sex was a possible risk factor, whereas smoking was negatively associated with the risk of SARS-CoV-2 infection, when comparing PCR-positive cases and PCR- negative controls. Asthma was associated with the risk of SARS-CoV-2 infection when PCR- positive cases were compared with population controls.