ABSTRACT
Programmed death 1 (PD-1) has a central role in maintaining T cell tolerance and terminating cellular responses after eliminating antigens. Variation in PD-1 gene products caused by polymorphisms has been linked to several malignancies and autoimmune diseases. However, there is little known about the effects of its single-nucleotide polymorphisms (SNPs) on viral infections, particularly COVID-19. The primary aim of this study was to explore the function of genotypes, alleles, and haplotypes of two SNPs within the programmed cell death protein 1 (PDCD1) gene at PD1.3 G/A and PD1.5 C/T on susceptibility to COVID-19 in an Iranian population. The secondary objective was to evaluate the effects of these SNPs on the outcome of the disease. We got blood samples from COVID-19 patients (n = 195) and healthy subjects (n = 500) for genotypic determination of PD1.3 G/A (rs11568821) and PD1.5 C/T (rs2227981) SNPs, using the polymerase chain reaction-restriction fragment length polymorphism method, and constructed four haplotypes for PDCD1 SNPs. We used Pearson's chi-squared test, Fisher's exact test, and T-test for this study and incorporated effect sizes of odds ratio (OR) and standardized mean difference. The frequency of CT genotype of PD1.5 was meaningfully higher in COVID-19 patients (49.2%) than in healthy subjects (37.4%) (p = 0.005). However, these significant differences were not observed in the frequencies of PD1.3 genotypes between the two groups (p > 0.05). Of all estimated haplotypes for PDCD1, only AT was significantly and largely associated with COVID-19 susceptibility (p = 0.01, OR: 7.79 [95% confidence interval = 1.56-38.79]), however, this finding is inconclusive. In addition, the present study showed that the PD1.3 and PD1.5 SNPs were not associated with the outcome of the disease (p > 0.05). These results may propose that the PD1.5 CT genotype and AT haplotype of PDCD1 indecisively contribute to COVID-19 susceptibility in the Iranian population.
ABSTRACT
An ongoing pandemic of newly emerged SARS-CoV-2 has puzzled many scientists and health care policymakers around the globe. The appearance of the virus was accompanied by several distinct antigenic changes, specifically spike protein which is a key element for host cell entry of virus and major target of currently developing vaccines. Some of these mutations enable the virus to attach to receptors more firmly and easily. Moreover, a growing number of trials are demonstrating higher transmissibility and, in some of them, potentially more serious forms of illness related to novel variants. Some of these lineages, especially the Beta variant of concern, were reported to diminish the neutralizing activity of monoclonal and polyclonal antibodies present in both convalescent and vaccine sera. This could imply that these independently emerged variants could make antiviral strategies prone to serious threats. The rapid changes in the mutational profile of new clades, especially escape mutations, suggest the convergent evolution of the virus due to immune pressure. Nevertheless, great international efforts have been dedicated to producing efficacious vaccines with cutting-edge technologies. Despite the partial decrease in vaccines efficacy against worrisome clades, most current vaccines are still effective at preventing mild to severe forms of disease and hospital admission or death due to coronavirus disease 2019 (COVID-19). Here, we summarize existing evidence about newly emerged variants of SARS-CoV-2 and, notably, how well vaccines work against targeting new variants and modifications of highly flexible mRNA vaccines that might be required in the future.