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Background: Longitudinal surveys to monitor the seroprevalence are required to support efforts for assessment of the levels of endemic stability in certain countries. We investigated seroprevalence of anti-SARS-CoV-2-S1 receptor-binding domain (RBD)-specific antibodies in the serum samples in 2011–2021, including a cohort study of 2019–2021, to evaluate the vaccination and anti-IgG-SARS-CoV-2–S1 RBD-positive statuses to assess the resistance and severity of COVID-19. Materials and Methods: Anti-SARS-CoV-2-S1 RBD-specific antibodies were assayed in the serum samples (N = 565) randomly selected from various cohorts previously recruited from 2011 to 2021 from the city of Moscow and Moscow Region. Among them there were the participants (N = 310) recruited in 2019–2021 with an endpoint of 30 October 2021 when these participants were interviewed over phone with relevant questionnaire. Results: Obtained data indicated a percentage of 3–6% of SARS-CoV-2-S1 RBD-specific antibodies detected in participants recruited in 2011–2019. The percentage of SARS-CoV-2-S1 RBD-specific antibodies was increased to 16.5% in 2020 and to 46% in 2021. The vaccination rate of 238 respondents of this cohort was 58% from August 2020 to October 2021. In total, 12% of respondents were hospitalized. The morbidity rate in the subgroup of anti-SARS-CoV-2-S1 RBD-positive respondents was 5.4-fold higher than that in the subgroup of vaccinated respondents. Conclusions: A small percentage of SARS-CoV-2-S1 RBD-specific antibodies detected in 2011–2019 indicated possible spreading of coronaviruses during the pre-pandemic period. Collective immunity in Moscow and the Moscow region was able to reach 69% from August 2020 to October 2021 if this rate is added to the rate of not vaccinated SARS-CoV-2-S1 RBD-positive subjects.

Detection of Anti-SARS-CoV-2-S1 RBD-Specific Antibodies Prior to and during the Pandemic in 2011–2021 and COVID-19 Observational Study in 2019–2021