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. 2022 Aug 8;111:109128. doi: 10.1016/j.intimp.2022.109128

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Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Fig. 2 — The roles of immune-related genes in COVID-19. As illustrated, some HLA variants are associated with susceptibility to SARS-CoV-2 such as HLA-DRB1*0301, DRB1*14:04, DRB1*01:01, DRB1*04:01, DRB1*07:01, HLA-B*4601, B*0703, B*51:01, and B*40:01. Also, heterozygote HLA-E*0101/0103 can attenuate the NKG2C⁺ NK cell responses. The infection of a cell with SARS-CoV-2 could result in the secretion of type I IFNs which consequently interact with adjacent IFNR1/2-expressing cells to initiate the signaling pathway ending in anti-viral responses; however, the presence of rs74956615 in TYK2^__endocing a tyrosine kinase-related to IFNR1 signaling^__ induces TYK2 overexpression, and consequently, hurts the lung cells. Moreover, rs10735079 in TYK2 is associated with reduced OAS expression and attenuated anti-viral responses. Notably, some SNPs in OAS and MX1 could elevate the risk of COVID-19, as well. Similarly, mutations in IRF7 and IRF9^__components of IFN signaling pathway^__ boost SARS-CoV-2 susceptibility. rs12252 in IFITM3 also attenuates the ability of IFITM3 to block the entrance of viral products into the cells. CCR1 and CCR2-MCP-1 could enhance the infiltartion of monocytes and macrophages and induce inflammation; with this regard, the pressence of activating variants in CCR1 and CCR2 has been observed in critically ill COVID-19 patients. Besides, the lower expression of CXCR6 could reduce the infiltration of CD8⁺ T cells in the lung, leading to more severe disease. The mutations in TLRs such as the deletion in TICAM2, which is related to TLR-4 initial signaling, could influence the risk of COVID-19. Similarly, loss-of-function of TLR-3 and TLR-7 impairs the IFNs responses. The overexpression of complement system components is another agent magnifying the severity of the disease. In patients carrying rs11385949, the levels of upper airway viral load and sC5b-9 were greater than others. Regarding the roles of DBP in the regulation of vitamin D levels, patients harboring GC rs2282679 could experience the severe type of the disease. Furthermore, The NK cells isolated from severe cases of COVID-19 have shown higher expression of NKG2C and secretion of perforin. Moreover, it was shown that Cit-H3 has significant roles in NET formation and consequently higher inflammation and cardiovascular complications.