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Background: Nation-wide SARS-CoV-2 seroprevalence surveys provide valuable insights into the course of the pandemic, including information often not captured by routine surveillance of reported cases. Methods: A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between March and December 2020. It was designed as a cross-sectional survey repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Results: Of 55,947 serum samples collected, 705 (1.26%) were found positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (9.09%) observed in December 2020. Highest seropositivity levels were observed in the “0–29” and “30–49” year age groups. Seroprevalence increased with age in the “0–29” age group. Highly populated metropolitan areas were characterized with elevated seroprevalence levels (11.92% in Attica, 12.76% in Thessaloniki) compared to the rest of the country (5.90%). The infection fatality rate (IFR) was estimated at 0.451% (95% CI: 0.382–0.549%) using aggregate data until December 2020, and the ratio of actual to reported cases was 9.59 (7.88–11.33). Conclusions: The evolution of seroprevalence estimates aligned with the course of the pandemic and varied widely by region and age group. Young and middle-aged adults appeared to be drivers of the pandemic during a severe epidemic wave under strict policy measures.

SARS-CoV-2 Sero-Surveillance in Greece: Evolution over Time and Epidemiological Attributes during the Pre-Vaccination Pandemic Era