Genetic Predisposition to SARS-CoV-2 Infection: Cytokine Polymorphism and Disease Transmission within Households

SIMPLE SUMMARY: Soluble factors, the cytokines, influence the ability of an individual host defense against intruders, e.g., the SARS-CoV-2 virus. Distinct T cells are a major source of many of those molecules. The helper T cells are divided into categories according to their action on the immune response: the more pro-inflammatory helper T cells 1 (Th1: TNF-α, IFN-γ), the anti-inflammatory (Th2: IL-10) cells, and the more regulatory Th17 (IL-17, TGF-β1) and Treg (TGF-β1) cells. In the present report, we elaborate on the genetically determined activity of such cytokines, regarding defined polymorphisms with known impact on the cytokine expression and their influence on the course of SARS-CoV-2 infection. We selected from a larger cohort individuals from the same household (n = 58). We divided them into households with all individuals SARS-CoV-2-PCR positive (n = 29) with 61 individuals, mixed households (n = 24) with 62 individuals and households (n = 5) with 15 SARS-CoV-2-negative individuals and compared the frequency of distinct polymorphisms. The results obtained indicate a role for a genetically determined balance of the different T helper cell pathways. ABSTRACT: We addressed the question of the influence of the molecular polymorphism of cytokines from different T helper subsets on the susceptibility to SARS-CoV-2 infection. From a cohort of 527 samples (collected from 26 May 2020 to 31 March 2022), we focused on individuals living in the same household (n = 58) with the SARS-CoV-2-infected person. We divided them into households with all individuals SARS-CoV-2 PCR positive (n = 29, households, 61 individuals), households with mixed PCR pattern (n = 24, 62) and negative households (n = 5, 15), respectively. TGF-β1 and IL-6 were the only cytokines tested with a significant difference between the cohorts. We observed a shift toward Th2 and the regulatory Th17 and Treg subset regulation for households with all members infected compared to those without infection. These data indicate that the genetically determined balance between the cytokines acting on different T helper cell subsets may play a pivotal role in transmission of and susceptibility to SARS-CoV-2 infection. Contacts infected by their index persons were more likely to highly express TGF-β1, indicating a reduced inflammatory response. Those not infected after contact had a polymorphism leading to a higher IL-6 expression. IL-6 acts in innate immunity, allergy and on the T helper cell differentiation, explaining the reduced susceptibility to SARS-CoV-2.