The Association of Programmed Death 1 Gene Polymorphisms of PD1.3 G/A and PD1.5 C/T with Risk of COVID-19 in an Iranian Population: A Case-Control Study.

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.

Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities.

Although cellular and molecular mediators of the immune system have the potential to be prognostic indicators of disease outcomes, temporal interference between diseases might affect the immune mediators, and make them difficult to predict disease complications. Today one of the most important challenges is predicting the prognosis of COVID-19 in the context of other inflammatory diseases such as traumatic injuries. Many diseases with inflammatory properties are usually polyphasic and the kinetics of inflammatory mediators in various inflammatory diseases might be different. To find the most appropriate evaluation time of immune mediators to accurately predict COVID-19 prognosis in the trauma environment, researchers must investigate and compare cellular and molecular alterations based on their kinetics after the start of COVID-19 symptoms and traumatic injuries. The current review aimed to investigate the similarities and differences of common inflammatory mediators (C-reactive protein, procalcitonin, ferritin, and serum amyloid A), cytokine/chemokine levels (IFNs, IL-1, IL-6, TNF-α, IL-10, and IL-4), and immune cell subtypes (neutrophil, monocyte, Th1, Th2, Th17, Treg and CTL) based on the kinetics between patients with COVID-19 and trauma. The mediators may help us to accurately predict the severity of COVID-19 complications and follow up subsequent clinical interventions. These findings could potentially help in a better understanding of COVID-19 and trauma pathogenesis.

Predictive monitoring and therapeutic immune biomarkers in the management of clinical complications of COVID-19.

The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), appears with a wide spectrum of mild-to-critical clinical complications. Many clinical and experimental findings suggest the role of inflammatory mechanisms in the immunopathology of COVID-19. Hence, cellular and molecular mediators of the immune system can be potential targets for predicting, monitoring, and treating the progressive complications of COVID-19. In this review, we assess the latest cellular and molecular data on the immunopathology of COVID-19 according to the pathological evidence (e.g., mucus and surfactants), dysregulations of pro- and anti-inflammatory mediators (e.g., cytokines and chemokines), and impairments of innate and acquired immune system functions (e.g., mononuclear cells, neutrophils and antibodies). Furthermore, we determine the significance of immune biomarkers for predicting, monitoring, and treating the progressive complications of COVID-19. We also discuss the clinical importance of recent immune biomarkers in COVID-19, and at the end of each section, recent clinical trials in immune biomarkers for COVID-19 are mentioned.