Using SARS-CoV-2 anti-S IgG levels as a marker of previous infection: example from an Israeli healthcare worker cohort.

Objectives: Determining COVID-19 status is important for global epidemiology and individual-level vaccination decision-making. SARS-CoV-2 infection can generally only be detected during a 7–10-day period using polymerase chain reaction or rapid antigen testing, and infection-specific antinucleocapsid IgG assays are not universally available. We determined whether SARS-CoV-2 antispike (anti-S) IgG levels could discriminate between vaccination and previous infection when interpreted alongside vaccination timing. Methods: We measured SARS-CoV-2 anti-S-IgG level in 535 vaccinated Israeli healthcare workers with known previous infection status 6–8 months after the second dose. Results: Anti-S IgG levels above 1000 AU/ml at that time point was 93.3% predictive of infection in the previous 3 months, whereas the negative predictive value for infection in the past 3 months of a level below that threshold was 99.5%. Conclusion: When interpreted alongside vaccination timing, anti-S serological assays can confirm or exclude previous infections within the previous 3 months.