Polymorphism of TLR genes and the course of COVID-19 bilateral pneumonia

Abstract

BACKGROUND: COVID-19 is a disease which course depends on a number of factors, including genetic ones, among which the genes of the innate immune system receptors – TLR (toll-like receptors), which play a central role in the development of innate immunity reactions, are of particular interest. The SARS-CoV-2 virus structure includes, in addition to the nucleocapsid, a protein-lipid membrane envelope, which determines the recognition of virus components by different TLRs, including TLR2 subfamily receptors (TLR1, 6, 10), which genetic polymorphisms occur with different frequencies in different human populations and affect not only the functional activity of the innate immunity but also determine the quality of the adaptive immune response.

AIM: The study aimed to determine the association of polymorphisms of toll-like receptor genes TLR1, TLR6 and TLR10 with the severity of coronavirus infection (COVID-19) in the Russian population of the Chelyabinsk region.

MATERIALS AND METHODS: The study included 86 patients from COVID-departments of hospitals in Chelyabinsk with a diagnosis of bilateral pneumonia with a degree of severity: moderate (M-BLP, n = 36) or severe (S-BLP, n = 50). The control group consisted of 100 healthy individuals from the register of the Chelyabinsk regional hemotransfusion station (“Control”). All the individuals studied belonged to the Russian ethnic group. Polymorphisms 1805T>G of TLR1 gene, 745C>T of TLR6 gene and 721A>C of TLR10 gene were determined using polymerase chain reaction with restriction fragment length polymorphism. The analysis of the association between genotypes and the status of individuals was carried out using the correspondence analysis and the Monte Carlo method.

RESULTS: It was revealed that the differences between the studied groups are completely determined by TLR1 genotypes. The GG genotype with statistical significance is more often detected in the “Control” group compared to M-BLP and S-BLP (p < 0.001, OR = 12.94) and can be assessed as protective in relation to the development of bilateral pneumonia in COVID-19. The TT genotype can be considered as predisposing to the development of a severe form of bilateral pneumonia in COVID-19 (p = 0.022): the TT genotype is significantly less common (OR = 0.20) in the M-BLP group compared to S-BLP.

CONCLUSIONS: It can be assumed that the genetic variant 1805*G of the TLR1 gene, which provides a moderate pro-inflammatory response and predominates in European populations, gives an advantage to its owners, preventing the development of complicated conditions in COVID-19 infection.

Keywords

COVID-19 / TLR / genetic polymorphism / bilateral pneumonia / immunogenetics

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Evdokimov A.V., Suslova T.A., Belyaeva S.V., Burmistrova A.L., Stashkevich D.S.