Modulation of TLR7, TYK2 and OAS1 expression during SARS-CoV-2 infection

The host response to SARS-CoV-2 depends on multiple factors including age, gender, underlying diseases and genetic background. Viral sensing and activation of the interferon signaling pathway in the early antiviral response could affect disease outcome. This study evaluated gene expression of Toll-like receptor 7 (TLR7), tyrosine kinase 2 (TYK2) and 2'-5' oligoadenylate synthetase 1 (OAS1) in two early longitudinal samples from mild, moderate and severe cases.

Demographic and clinical variables were obtained from 157 COVID-19 patients. Peripheral blood mononuclear cells were used for genotyping and gene expression determination, and plasma for viremia detection, by qPCR and digital PCR, respectively. Gene expression was analyzed using Generalized Linear Mixed Models nested by patient. First, univariate analyses determined which variables were significantly associated with gene expression. Next, multivariate models were built with these variables, following the backward method.

TLR7 levels were higher in patients with mild disease compared to those with moderate disease and decreased over time. In contrast, patients with severe disease had lower TLR7 expression, which remained stable. OAS1 behavior was similar, whereas TYK2 remained unchanged. Multivariate analysis confirmed the relation of low TLR7 expression with severity and viremia. OAS1 levels directly correlated with higher viremia. TYK2 was associated with OAS1 expression, and OAS1 with both TLR7 and TYK2 levels.

Low TLR7 levels were associated with severe COVID-19, and together with OAS1 expression were modulated over time according to severity. While TLR7 expression decreased across all severity groups as the disease resolved, OAS1 expression persisted in severe cases with higher viremia.