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

Meltendorf, Stefan; Vogel, Katrin; Thurm, Christoph; Prätsch, Florian; Reinhold, Annegret; Färber, Jacqueline; Heuft, Hans-Gert; Kaasch, Achim J.; Hachenberg, Thomas; Weinzierl, Stefan; Schraven, Burkhart; Reinhold, Dirk; Brunner-Weinzierl, Monika C.; Lingel, Holger

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.
Published in: European Journal of Immunology, 10.1002/eji.202249951, Wiley