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

• Published in: Journal of medical virology Vol. 94; no. 9; pp. 4088 - 4096
• Main Authors: Vakil, Mohammad Kazem, Mansoori, Yaser, Al‐Awsi, Ghaidaa Raheem Lateef, Hosseinipour, Ali, Ahsant, Samaneh, Ahmadi, Sedigheh, Ekrahi, Mohammad, Montaseri, Zahra, Pezeshki, Babak, Mohaghegh, Poopak, Sohrabpour, Mojtaba, Bahmanyar, Maryam, Daraei, Abdolreza, Dadkhah Jouybari, Tahereh, Tavassoli, Alireza, Ghasemian, Abdolmajid
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-09-2022; John Wiley and Sons Inc
• Subjects: Chemokines; coronavirus disease‐19; Coronaviruses; COVID-19; Cytokine receptors; Cytokines; Gene expression; Gene polymorphism; Genes; Genetic diversity; Genetic variability; genetic variations; Immune system; immunity; Infections; Inflammation; Interferon; Interleukin 10; Interleukin 17; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes B; Lymphocytes T; Monocytes; Mutation; Natural killer cells; Nucleotides; Pathophysiology; Patients; Proteins; Receptors; Respiratory diseases; Review; Reviews; Severe acute respiratory syndrome; Signs and symptoms; Single-nucleotide polymorphism; TLR3 protein; TLR7 protein; TLR9 protein; Toll-like receptors; Tumor necrosis factor; Viral diseases; Viral infections; Virology; cytokines; coronavirus disease-19; immunity; toll-like receptors; genetic variations
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.27849

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.