Individual genetic variability mainly of Proinflammatory cytokines, cytokine receptors, and toll‐like receptors dictates pathophysiology of COVID‐19 disease

Abstract

Innate and acquired immunity responses are crucial for viral infection elimination. However, genetic variations in coding genes may exacerbate the inflammation or initiate devastating cytokine storms which poses severe respiratory conditions in coronavirus disease-19 (COVID-19). Host genetic variations in particular those related to the immune responses determine the patients' susceptibility and COVID-19 severity and pathophysiology. Gene polymorphisms such as single nucleotide polymorphisms (SNPs) of interferons, TNF, IL1, IL4, IL6, IL7, IL10, and IL17 predispose patients to the severe form of COVID-19 or severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). These variations mainly alter the gene expression and cause a severe response by B cells, T cells, monocytes, neutrophils, and natural killer cells participating in a cytokine storm. Moreover, cytokines and chemokines SNPs are associated with the severity of COVID-19 and clinical outcomes depending on the corresponding effect. Additionally, genetic variations in genes encoding toll-like receptors (TLRs) mainly TLR3, TLR7, and TLR9 have been related to the COVID-19 severe respiratory symptoms. The specific relation of these mutations with the novel variants of concern (VOCs) infection remains to be elucidated. Genetic variations mainly within genes encoding proinflammatory cytokines, cytokine receptors, and TLRs predispose patients to COVID-19 disease severity. Understanding host immune gene variations associated with the SARS-COV-2 infection opens insights to control the pathophysiology of emerging viral infections.

Zonulin, a marker of gut permeability, is associated with mortality in a cohort of hospitalised peruvian COVID-19 patients

“…Inflammatory responses to viral infection are also influenced by genetic background, for example individual genetic variability of pro-inflammatory cytokines is related to severity in COVID-19 ( Vakil et al., 2022 ). Moreover, population-associated variation of responses to viral infections is differentiated by genetic ancestry ( Randolph et al., 2021 ).…”

Role of SNPs of IL6 gene in the incidence and progression of COVID19 patients in Wasit province

“…The role of rs13306435 in HCC has been confirmed by meta-analysis (HCC) [1], [7], [21]. SNPs rs13306435 (-395T > A), rs2069860 (-623A > T), and rs2069830 (-612A > T) were shown to have a substantial correlation with cervical cancer susceptibility in the Lithuanian population in a separate research that evaluated two IL-6 genetic polymorphisms (rs13306435 and rs2069830) [6], [15], [16].…”

“…There was a correlation between the 395 A/T rs2069830) SNP and COPD in Caucasians but not in North Indians. One research found an association between the IL-6 rs2069830 (-612A > T) CC gene variant and the risk of dying from septic shock in Caucasian Europeans who had heart or abdominal surgery [16], [17]. Researchers from China discovered that those with the IL-6-395 TT genotype had a significantly increased likelihood of developing pneumonia-induced sepsis and mRNA levels [18]- [20].…”

Diagnosis and Stratification of COVID-19 Infections Using Differential Plasma Levels of D-Dimer: A Two-Center Study from Saudi Arabia

“…Studies have also indicated a high infectivity potential and increased severity of COVID-19 in the A blood group serotype, while the O blood group serotype is observed to be protective against infection [18]. Genetic polymorphism, SNPs, in-host immune response genes, including interferons, TNF, and interleukins, are attributed to inducing a high COVID-19 severity [19]. Additionally, besides the genetic and immune determinants, age and gender association has been widely observed in COVID-19 infectivity and severity [20,21].…”