IL‐13 determines specific IgE responses and SARS‐CoV‐2 immunity after mild COVID‐19 and novel mRNA vaccination

After recovery, mild and severe COVID‐19 diseases are associated with long‐term effects on the host immune system, such as prolonged T‐cell activation or accumulation of autoantibodies. In this study, we show that mild SARS‐CoV‐2 infections, but not SARS‐CoV‐2 spike mRNA vaccinations, cause durable atopic risk factors such as a systemic Th2‐ and Th17‐type environment as well as activation of B cells responsive of IgE against aeroallergens from house dust mite and mold. At an average of 100 days post mild SARS‐CoV‐2 infections, anti‐mold responses were associated with low IL‐13 levels and increased pro‐inflammatory IL‐6 titers. Acutely severely ill COVID‐19 patients instead showed no evidence of atopic reactions. Considering convalescents of mild COVID‐19 courses and mRNA‐vaccinated individuals together, IL‐13 was the predominant significantly upregulated factor, likely shaping SARS‐CoV‐2 immunity. Application of multiple regression analysis revealed that the IL‐13 levels of both groups were determined by the Th17‐type cytokines IL‐17A and IL‐22. Taken together, these results implicate a critical role for IL‐13 in the aftermath of SARS‐CoV‐2 mild infections and mRNA vaccinations, conferring protection against airway directed, atopic side reactions that occur in mildly experienced COVID‐19.