The susceptibility to adverse outcome from critical injury (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. We assessed the relationship of the genotype distribution of various cytokine gene polymorphisms (CGP) with regard to the development of sepsis, organ dysfunction or mortality in severely injured patients. Observational, hospital-based cohort study of 114 severely injured North Indian patients from New Delhi admitted to the Emergency Department (ED) of Trauma Centre, AIIMS. Patients were monitored from day first to discharge or death, measuring SOFA score, sepsis and septic shock occurrences up to one month. We have analyzed 13 cytokine genes, including the SNPs of structural and regulatory regions at 22 positions. Sequence-specific primer based PCR indicated that eight polymorphic loci IL-1α /-889, IL-1β/-511, IL-1R (pstI 1970), TGF-β/ code 10, TNF-α/-308, TNF-α/-238, IL-6/+565 and IL-10/-1082, out of 22 SNPs are significantly associated with sepsis morbidity and outcome. Theses SNPs might be used as risk determinants of the outcome. Patients with IL-10 (−1082A/A) genotypes were found significantly higher in post traumatic sepsis patients and had a significantly higher risk to developed sepsis complication (p < 0.05, OR = 0.86, C.I = 0.08-8.8).In case of TNF-α (−308) position, GA and GG genotype patients have a significantly lower risk of poor outcome (p < 0.05, OR = 0.25, C.I = 0.01-1.3) and (p < 0.05, OR = 0.22, C.I = 0.01-0.5) in comparison to AA genotype. In this study, two polymorphisms (IL-1β (−511) and IL-1R) were significantly associated with the development of MOF and mortality, where as IL-1α (−889) polymorphism associated with susceptibility for sepsis. The distribution of haplotypes of TGF-β and IL-6 were also associated with sepsis susceptibility and outcome. In conclusion, we have found that the alternations in the genotype and allele frequency of IL-1β (−511C/T), TNF-α (−308 G/A), TNF-α (−238 G/A) and IL-10 (−1082 G/A) genes are associated with an higher risk of sepsis development in trauma patients and outcomes.

Introduction: It is unclear whether induced spike protein-specific antibodies due to infections with SARS-CoV-2 or to the prototypic Wuhan isolate-based vaccination can immune-react with the emerging variants of SARS-CoV-2. Aim/objectives: The main objective of the study was to measure the immunoreactivity of induced antibodies postvaccination with Covishield™ (ChAdOx1 nCoV-19 coronavirus vaccines) or infections with SARS-CoV-2 by using selected peptides of the spike protein of wild type and variants of SARS-CoV-2. Methodology: Thirty patients who had recovered from SARS-CoV-2 infections and 30 individuals vaccinated with both doses of Covishield™ were recruited for the study. Venous blood samples (5 mL) were collected at a single time point from patients within 3-4 weeks of recovery from SARS-CoV-2 infections or receiving both doses of Covishield™ vaccines. The serum levels of total immunoglobulin were measured in both study groups. A total of 12 peptides of 10 to 24 amino acids length spanning to the receptor-binding domain (RBD) of wild type of SARS-CoV-2 and their variants were synthesized. The serum levels of immune-reactive antibodies were measured using these peptides. Results: The serum levels of total antibodies were found to be significantly (p<0.001) higher in the vaccinated individuals as compared to COVID-19 recovered patients. Our study reported that the mutations in the RBD at the residues K417, E484, and N501 have been associated with reduced immunoreactivity with anti-sera of vaccinated people and COVID-19 recovered patients. Conclusion: The amino acid substitutions at the RBD of SARS-CoV-2 have been associated with a higher potential to escape the humoral immune response.

The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and diversity in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet characterized. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria; especially antibiotics resistance bacteria. The altered composition and diversity of gut microbiota especially AMR bacteria due to treatment with antibiotics may lead to the translocation of enteric bacteria across the epithelium and causes the pathogenesis of sepsis. Disruptions of gut microbiota diversity are directly associated with susceptibility to sepsis and a higher risk of adverse outcomes. Several studies have confirmed that a mutual association between gut microbiota and the host is important for the metabolism of essential nutrients for the organism, for gut development, and the maturation and development of a fully functional immune system. Therefore, depth knowledge of the gut microbiota diversity, composition, and function during various inflammatory conditions and sepsis may provide a comprehensive understanding of the mechanisms behind the pathogenesis of gut-derived infection in diseases and the design of new treatment options (e.g., probiotics or fecal microbiota transplantation). Emerging evidence display an important role of gut microbiota and their derived metabolites in modulating the host mucosal immune response and determining the susceptibility to, as well as outcomes of sepsis.