Iran is one of the countries that have been confronted with the SARS-CoV-2 epidemic since February 2020. This study aimed to determine the levels of specific IgG antibodies against SARS-CoV-2 among healthy blood donors to estimate the burden of the epidemic.

A serial cross-sectional study was conducted on blood donors who referred to 31 main blood donation centers in different provinces during the third weeks of September, October, and November 2020. A questionnaire was filled out to collect socio-demographic characteristics, history of contact with COVID-19 patients, and history of COVID-19. A blood sample was collected from each participant to assess the antibodies against SARS-CoV-2 using the ELISA method. The crude prevalence of anti-SARS-CoV-2 IgG was calculated. Then it was weighted based on the gender and age groups of the general population in each province and adjusted for test sensitivity and specificity.

During three time points of the study, 3840, 3697, and 3152 participants enrolled. The seroprevalence of SARS-CoV-2 IgG antibodies was 19.59% (17.18–22.00), 22.67% (20.70–24.65), and 32.63% (29.93–35.33) over the three rounds of the study.

We found an association between the seropositivity and the highest educational level; AOR 0.76 (0.63–0.93), history of close contact with COVID-19 patients; AOR 1.69 (1.35–2.11), and history of confirmed SARS-CoV-2 infection; AOR 8.86 (5.38–14.60).

This study showed that about one-third of the population had been infected with COVID-19. Furthermore, a significant upward trend in seroprevalence was observed. The predisposing factors indicate the importance of public health.