Journal of Population Therapeutics & Clinical Pharmacology

The SARS-CoV-2 virus causes a contagious disease known as Coronavirus Disease 2019 (COVID-19). It began spreading globally in 2019 and is still producing pandemics today. Different COVID-19 vaccinations offer protection against this illness. Pfizer-BioNTech and Sinopharm were the two vaccine manufacturers with the highest usage in Iraq. Both vaccines use a different method to activate the immune system. This study seeks to compare the IL-22, IL-37, and IL-38 levels in those who received either the Sinopharm or the Pfizer-BioNTech COVID-19 vaccination. IL-22, IL-37, IL-38 levels have been shown to be upregulated in COVID-19 patients. In this study, IL-22, IL-37, and IL -38 levels were tested in 80 healthy controls and 100 COVID-19 patients 14-21 days after recovery. Additionally, people who received the Sinopharm or Pfizer-BioNTech vaccine (50 each) were monitored 21 days after the first dosage and 21 days after the second dose. In comparison to controls, serum levels were noticeably higher in recovered patients. Except for the first dosage of Pfizer BioNTech, the first and second doses of Sinopharm and Pfizer BioNTech were linked to considerably higher levels of IL-22, IL-37, and IL-38 compared to controls or recovered patients. where IL-22, IL -37, and IL-38 levels did not show significant differences compared to recovered patients. In conclusion, lower IL-37 and IL-38 molecule levels were linked to recovery from COVID-19, although these levels remained considerably greater in recovered patients compared to uninfected controls. Vaccination with Sinopharm or Pfizer-BioNTech confirmed the up-regulating effects of SARS-CoV-2 on IL-22, IL-37, and IL-38 levels.

Aryl Hydrocarbon Receptor Activation Ameliorates Acute Respiratory Distress Syndrome through Regulation of Th17 and Th22 Cells in the Lungs.

Acute respiratory distress syndrome (ARDS) is triggered by a variety of insults, including bacterial and viral infections, and this leads to high mortality. While the role of the aryl hydrocarbon receptor (AhR) in mucosal immunity is being increasingly recognized, its function during ARDS is unclear. In the current study, we investigated the role of AhR in LPS-induced ARDS. AhR ligand, indole-3-carbinol (I3C), attenuated ARDS which was associated with a decrease in CD4+ RORγt +IL-17a+IL-22+ pathogenic Th17 cells, but not CD4+RORγt +IL-17a+IL-22- homeostatic Th 17 cells, in the lungs. AhR activation also led to a significant increase in CD4+IL-17a-IL-22+ Th22 cells. I3C-mediated Th22 cell expansion was dependent on the AhR expression on RORγt+ cells. AhR activation downregulated miR-29b-2-5p in immune cells from the lungs, which in turn downregulated RORc expression and upregulated IL-22. Collectively, the current study suggests that AhR activation can attenuate ARDS and may serve as a therapeutic modality by which to treat this complex disorder. IMPORTANCE Acute respiratory distress syndrome (ARDS) is a type of respiratory failure that is triggered by a variety of bacterial and viral infections, including the coronavirus SARS-CoV2. ARDS is associated with a hyperimmune response in the lungs that which is challenging to treat. Because of this difficulty, approximately 40% of patients with ARDS die. Thus, it is critical to understand the nature of the immune response that is functional in the lungs during ARDS as well as approaches by which to attenuate it. AhR is a transcription factor that is activated by a variety of endogenous and exogenous environmental chemicals as well as bacterial metabolites. While AhR has been shown to regulate inflammation, its role in ARDS is unclear. In the current study, we provide evidence that AhR activation can attenuate LPS-mediated ARDS through the activation of Th22 cells in the lungs, which are regulated through miR-29b-2-5p. Thus, AhR can be targeted to attenuate ARDS.

Interleukin-22 and interleukin-33 show up-regulated levels in the serum of patients with mild/moderate Coronavirus disease 2019.

Background: This study analyzed serum concentrations of interleukin (IL)-22 and IL-33 (pro-inflammatory and anti-inflammatory cytokines) in 90 patients with mild/moderate coronavirus disease 2019 (COVID-19) and 90 healthy controls. Enzyme-linked immunosorbent assay kits were used to measure IL-22 and IL-33 concentrations. Results: Median (interquartile range) concentrations of IL-22 and IL-33 were significantly higher in patients than in controls (IL-22: 18.6 [18.0-19.3] vs. 13.9 [12.1-14.9] pg/mL, probability [p] < 0.001; IL-33: 37.8 [35.3-43.0] vs. 24.1 [23.0-26.2] pg/mL, p < 0.001). As indicated by the area under the curve (AUC), IL-22 and IL-33 were excellent predictors of COVID-19 (AUC = 0.95 and 0.892, respectively). Multinomial logistic regression analysis demonstrated that individuals with high production (> control median) of IL-22 (odds ratio = 17.80 [95% CI: 6.48-48.90]; p = 0.001) and IL-33 (odds ratio = 19.0 [95% CI: 7.4-48.6]; p = 0.001) were more likely to develop COVID-19. A positive correlation was found between IL-22 and IL-33 and both cytokines also showed positive correlations with granulocyte-to-lymphocyte ratio and erythrocyte sedimentation rate in all participants. Conclusions: IL-22 and IL-33 showed up-regulated concentrations in the serum of patients with mild/moderate COVID-19. Both cytokines may have prognostic value for COVID-19 along with their association with disease risk.

Abstracts of the BSG Annual Meeting

The proceedings contain 374 papers. The topics discussed include: optical biopsy with linked color imaging accurately predicts inflammation in ulcerative colitis;predicting use of opiates in patients with inoperable pancreatic cancer: a retrospective cohort study;unbiased clustering of breath signature in NAFLD identifies disease progression high-risk patient phenotype - 5 year study;prevalence of malnutrition screening;the association between IBD and mental ill health: a retrospective primary care cohort study;the interleukin 22//neutrophil axis is associated with treatment resistance in ulcerative colitis;neuromuscular dysfunction in patients with nausea and vomiting syndrome defined by body surface gastric mapping;two-tiered liver fibrosis assessment in primary care annual diabetic screening 3 year follow up;can an algorithm help in the difficult dilemma of upper gastrointestinal bleed and anticoagulant COVID-19 pandemic and alcohol-specific hospital admissions;and upper gastrointestinal hemorrhages and COVID-19: a nationwide cohort study of the pandemic's impact on hospitalizations.

LOSS of TOLERANCE and ANERGY in HUMAN PERIPHERAL B CELLS during SARS-CoV-2 INFECTION

Background: Severe infection with SARS-CoV-2 induces systemic autoreactive antibodies with specificity to Type I IFN, phospholipids, nuclear or tissue specific targets. The wide breadth of targets suggests a system-wide defect in B cell tolerance during viral infection and that the source of autoreactive antibodies is likely a heterogenous subset of B cells. BND cells are mature naïve B cells that do not express IgM but do express IgD and are enriched in autoreactive specificities. BND cells are held in an anergic state in healthy humans as a mechanism of peripheral tolerance, although in vitro evidence suggests anergy can be broken with strong inflammation. We hypothesized that robust inflammation associated with viral infection from SARS-CoV2 may relax peripheral tolerance and promote breakage of BND cell anergy. Methods: Plasma and PBMCs were collected from healthy controls (N=10), subjects immunized with Pfizer BNT162b2-mRNA/Moderna mRNA-1273 (N=10), subjects with mild (N=11) or severe SARS-CoV-2 infection (N=14). BND cells were examined ex vivo for markers of activation by flow cytometry. Phosphorylation of signaling proteins downstream of the BCR were measured in vitro with or without BCR crosslinking. Inflammatory cytokines were measured in plasma by multiplex. For statistical analysis, unpaired t test between populations or paired t test between unstimulated and BCR stimulated conditions were performed. Results: BND cells from severe SARS-CoV-2 infection have lower expression of CD21, associated with loss of anergy, higher expression of activation markers CD68 and CD86 with lower expression of inhibitory receptors CD22 and CD72 when compared to BND cells from other subjects, suggesting a phenotypical breach of anergy. Upon BCR crosslinking, BND cells have higher levels of downstream signaling components of the BCR (pPLCγ2, pBlnk, and pSyk) when compared to healthy controls and immunized subjects, suggesting a functional breach in anergy with infection. Examination of plasma from severe SARS-CoV-2 infection showed higher levels of inflammatory cytokines (IFNγ, TNFα, IL-6 and CRP) where TNFα and CRP correlated with enhanced BCR signaling in BND cells. Conclusion: We demonstrate that SARS-CoV-2 viral infection relaxes peripheral tolerance of BND cells, likely through strong systemic inflammation produced during infection. These autoreactive cells overcome anergy and become activated with increased BCR signaling. Thus BND cells could be a source of autoreactive antibodies during viral infection.