A bioinformatic approach to investigating cytokine genes and their receptor variants in relation to COVID‐19 progression

Abstract

Severe acute respiratory syndrome coronavirus 2 infection produces a wide spectrum of manifestations, ranging from no symptom to viral pneumonia. This study aimed to determine the genetic variations in cytokines and their receptors in relation to COVID‐19 pathogenesis using bioinformatic tools. Single nucleotide polymorphisms (SNPs) of genes encoding the cytokines and cytokine receptors elevated in patients with COVID‐19 were determined from the National Biotechnology Information Center website (using the dbSNP database). Missense variants were found in 3 cytokine genes and 10 cytokine receptor genes. Computational analyses were conducted to detect the effects of these missense SNPs via cloud‐based software tools. Also, the miRSNP database was used to explore whether SNPs in the 3′‐UTR altered the miRNA binding efficiency for genes of cytokines and their receptors. Our in silico studies revealed that one SNP in the vascular endothelial growth factor receptor 2 ( VEGFR2 ) gene was predicted as deleterious using sorting intolerant from tolerant. Also, the stability of VEGFR2 decreased in the I‐Mutant2.0 (biotool for predicting stability changes upon mutation from the protein sequence or structure) prediction. It was suggested that the decrease in VEGFR2 function (due to the rs1870377 polymorphism) may be correlated with the progression of COVID‐19 or contribute to the pathogenesis. Moreover, 27 SNPs were determined to affect miRNA binding for the genes of cytokine receptors. CXCR2 rs1126579, TNFRSF1B rs1061624 and IL10RB rs8178562 SNPs were predicted to break the miRNA‐mRNA binding sites for miR‐516a‐3, miR‐720 and miR‐328, respectively. These miRNAs play an important role in immune regulation and lung damage repair. Further studies are needed to evaluate the importance of these miRNAs and the SNPs.

Systems biology models to identify the influence of SARS-CoV-2 infections to the progression of human autoimmune diseases

“… [ 53 , 54 ] KDR 18 0.44144144 0.08063474 Involved in the development of COVID-19 and its leading pathogenesis; noticed several actions in the progression of RA. [ 55 , 56 ] STAT1 18 0.4516129 0.2131105 Aligned with immune response activities of SARS-CoV-2; involved in regulation of SARS-CoV-2 infected cells; [ 57 , 58 ] B2M 16 0.41350211 0.06292203 Engaged in AD; claimed to be regulated by ivermectin drug of SARS-CoV-2. [ 59 , 60 ] CD3G 16 0.406639 0.05465393 Detected in the cluster of blood immune cells (CD 4 + and CD 8 +) from COVID-19 patients.…”

PD-1highCXCR5–CD4+ Peripheral Helper T (Tph) cells Promote Tissue-Homing Plasmablasts in COVID-19

“…The significant difference in the frequency of activated PD-1 high CXCR5 − Tph cells between stable and progressive patients disappears over time, indicating that the prompt induction of activated PD-1 high CXCR5 − Tph cells might be critical for the promotion of tissue homing plasmablasts to effectively remove virus from inflamed tissues and thus linked with better clinical outcomes. Not only sex differences 3 , but also genetic backgrounds are reported to be related to T cell activation 46,47 and further analyses combined with these factors will lead to the more precise identification of patients at higher risk, and thus expected to be valuable for the development of personalized treatments.…”

Will a little change do you good? A putative role of polymorphisms in COVID-19

“…These SNPs would result in a break on the miRNA-mRNA binding sites specific for miR-516a-3p, miR-720, and miR-328, which are important for regulating CXCR2, TNFR and IL10RB, respectively. It has been suggested that the main cause of lung tissue grievance during the response against SARS-CoV-2 is an increase in these chemokine and cytokine receptors ( Karakas et al, 2020 ). Although IL-10 is a regulatory cytokine, its receptor subunit is also utilized in the assembly of the receptor for IFN-λ, which could exert an antiviral as well as pro-inflammatory activity during severe and unbalanced COVID-19 immune response.…”