To determine the effects of vaccination and past infection on innate immunity following SARS-CoV-2 infection, we analyzed the relationship between anti–SARS-CoV-2 S Abs and biomarkers associated with the deterioration of COVID-19 (IFN-λ3, C-reactive protein, lactate dehydrogenase, ferritin, procalcitonin, and D-dimer). Here, IFNL3 is linked to COVID-19.