SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 Milan outbreak

Objectives: The Milan metropolitan area in Northern Italy was among the most severely hit by the SARS-CoV-2 outbreak. The epidemiological trends of mild COVID-19 are however still unknown. The aim of this study was to examine the seroprevalence of SARS-CoV-2 infection in healthy asymptomatic adults, the risk factors, and laboratory correlates. Design: We conducted a cross-sectional study during the outbreak. Presence of anti-SARS-CoV-2 IgM/IgG antibodies against the Nucleocapsid protein was assessed by a lateral flow immunoassay. Setting: Blood center at a leading academic hospital serving as COVID-19 referral center. Participants: We considered a random sample of blood donors since the start of the outbreak (February 24th to April 8th 2020, n=789). Main outcome measures: The main outcome was the prevalence of IgG/IgM anti-SARS-CoV-2 antibodies . Results: The test had a 98.3% specificity and 100% sensitivity, and for IgG was validated in a subset by an independent ELISA against the Spike protein (N=34, P<0.001). At the start of the outbreak, the overall seroprevalence of SARS-CoV-2 was 4.6% (2.3 to 7.9; P<0.0001 vs. 120 historical controls). During the study period characterized by a gradual implementation of social distancing measures, there was a progressive increase in seroprevalence to 7.1% (4.4 to 10.8), due to a rise in IgG+ to 5% (2.8 to 8.2; P=0.004 for trend, adjusted weekly increase 2.7, SE 1.3%), but not of IgM+ (P=NS). At multivariate logistic regression analysis, seroconversion to IgG was more frequent in younger (P=0.043), while recent infections (IgM+) in older individuals (P=0.002). IgM+ was independently associated with higher triglycerides, eosinophils, and lymphocytes (P<0.05). Conclusions: SARS-CoV-2 infection was already circulating in Milan at the outbreak start. Social distancing may have been more effective in younger individuals, and by the end of April 4.4-10.8% of healthy adults had evidence of seroconversion. Asymptomatic infection may affect lipid profile and blood count.