Harnessing immunity: Immunomodulatory therapies in COVID-19.

An overly exuberant immune response, characterized by a cytokine storm and uncontrolled inflammation, has been identified as a significant driver of severe coronavirus disease 2019 (COVID-19) cases. Consequently, deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation. With these delicate dynamics in mind, immunomodulatory therapies have emerged as a promising avenue for mitigating the challenges posed by COVID-19. Precision in manipulating immune pathways presents an opportunity to alter the host response, optimizing antiviral defenses while curbing deleterious inflammation. This review article comprehensively analyzes immunomodulatory interventions in managing COVID-19. We explore diverse approaches to mitigating the hyperactive immune response and its impact, from corticosteroids and non-steroidal drugs to targeted biologics, including anti-viral drugs, cytokine inhibitors, JAK inhibitors, convalescent plasma, monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2, cell-based therapies (i.e., CAR T, etc.). By summarizing the current evidence, we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.

Serum 7-alfa-hydroxy-4-cholesten-3-one and fibroblast growth factor-19 as biomarkers diagnosing bile acid malabsorption in microscopic colitis and inflammatory bowel disease.

BACKGROUND: Bile acid malabsorption is common in microscopic colitis, irritable bowel syndrome with diarrhea, and inflammatory bowel disease. We investigated the diagnostic accuracy of 7-alfa-hydroxy-4-cholesten-3-one and compared it with fibroblast growth factor-19 as biomarkers for bile acid malabsorption. METHODS: We enrolled consecutively 109 chronic diarrhea patients with standard laboratory tests, fecal calprotectin, and endoscopy separated into six groups: n = 30 with active inflammatory bowel disease, n = 21 with inflammatory bowel disease in remission reporting >3 bowel movements per day, n = 21 with inflammatory bowel disease after surgery, n = 23 with irritable bowel syndrome with diarrhea, n = 14 with microscopic colitis and 11 healthy subjects (controls). We defined bile acid malabsorption as >3 bowel movements and lower fibroblast growth factor-19 (<60 pg/ml). RESULTS: Median levels of 7-alfa-hydroxy-4-cholesten-3-one in inflammatory bowel disease active were 53.1 ng/ml, inflammatory bowel disease remission were 52.2 ng/ml, inflammatory bowel disease after surgery were 85.7 ng/ml, irritable bowel syndrome with diarrhea were 7.5 ng/ml, microscopic colitis were 69.3 ng/ml, and healthy controls were 3.7 ng/ml. We estimate a 7-alfa-hydroxy-4-cholesten-3-one cutoff of 48.9 ng/ml with 82.6% sensitivity and 84.3% specificity for detecting bile acid malabsorption. Both 7-alfa-hydroxy-4-cholesten-3-one >48.9 ng/ml and fibroblast growth factor-19 (<60 pg/ml) were found in 52% of the patients, compared with those 8% of patients below this 7-alfa-hydroxy-4-cholesten-3-one cutoff (P < 0.001). Serum 7-alfa-hydroxy-4-cholesten-3-one correlated with the number of bowel movements/day (r = -0.709; P < 0.001) and correlated inversely with fibroblast growth factor-19 (r = -0.741; P < 0.001). CONCLUSIONS: Serum 7-alfa-hydroxy-4-cholesten-3-one above 48.9 ng/ml and fibroblast growth factor-19 below 60 pg/ml identify patients with diarrhea likely attributable to bile acid malabsorption with high diagnostic accuracy and they can be used as screening biomarkers for bile acid malabsorption in microscopic colitis and inflammatory bowel disease.

Serum Levels of Fibroblast Growth Factor 19 Correlate with the Severity of Diarrhea and Independently from Intestinal Inflammation in Patients with Inflammatory Bowel Disease or Microscopic Colitis.

BACKGROUND: In chronic diarrhea patients, massive over-reporting symptom-based criteria for functional bowel disorders are pitfalls. There is currently no objective biomarker that may provide a correct correlation with the severity of chronic diarrhea. To clarify the role of fibroblast growth factor-19 (FGF-19) as a biomarker of objective measurements of the severity of diarrhea in comparison with a patientreported outcome, based on the Bristol Stool Form (BSF) Scale. METHODS: Consecutive 100 patients with chronic diarrhea underwent standard investigations with laboratory tests, fecal calprotectin (FC), endoscopy with biopsies, and serum FGF-19. All patients and 14 healthy controls completed a diary recording, BSF, and stool frequency. RESULTS: We found that irritable bowel syndrome with diarrhea (IBS-D) n = 21/23 (91%) reported a high number on BSF ≥6, compared to patients with inflammatory bowel diseases (IBD) 56/77 (72%) with BSF ≥ 6 (P = .011). FGF-19 median serum levels were significantly lower in Microscopic colitis (0.010 pg/mL) and IBD patients (0.009 pg/mL) compare to IBS-D (266.9 pg/mL) and high levels in healthy subjects (463 pg/mL) (P < .001). Strong inverse correlation of FGF-19 with the stool frequency/day and stool index was found (r = -0.800, P < .001; r = -0.739, P < .001), independently from disease activity (r = -0.718, P = .001; r = -0.792, P = .001). CONCLUSION: Serum FGF-19 can become a new biomarker for evaluating the severity of diarrhea with objectively and independently from intestinal inflammation. FC and FGF-19 are predictive biomarkers for the organic cause of diarrhea.

Prevalence of Irritable Bowel Syndrome, Functional Dyspepsia and their Overlap in Bulgaria: a Population-Based Study.

AIMS: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and their overlap syndrome (OS) in the Bulgarian population and to assess the risk factors associated with these disorders. METHODS: We sent an internet-based survey to Bulgarian adults. The survey collected data on socio- demographic, behavioral and lifestyle characteristics, and diagnostic questions following the Rome IV criteria to assess IBS, FD and their overlap occurrence. RESULTS: Data was collected from 1,896 individuals (mean age = 35.5 years, 18-65, SD=11.7), 73.1% females. The prevalence of IBS was 20% (14% were with predominant constipation, 32% with predominant diarrhea, 52% had IBS with mixed bowel habits, and 2% unclassified IBS). Gender (p=0.005), age (p<0.001), marital status (p=0.009), occupation (p=0.001), alcohol consumption (p=0.013), sexual problems (p<0.001), FD (p<0.001), and milk intolerance (p<0.001) were significantly associated with IBS. Females (p=0.032; OR: 1.50), patients with FD (p<0.001; OR: 104.98), sexual problems (p= 0.001; ОR: 1.55 ), and milk intolerance (p<0.001; OR: 2.22) are at a higher risk of having IBS. The prevalence of FD was 12.7% (39% had postprandial distress syndrome, 33% epigastric pain syndrome, and 28% had the overlapping variant). Patients with IBS (p<0.001; OR: 127.88) and milk intolerance (p<0.001) were significantly associated with FD prevalence. The prevalence of OS was 11.7%. Gender (p=0.013), milk intolerance (p<0.001, OR: 1.65), urinary (p=0.035) and sexual problems (p<0.001, ОR: 1.80) were associated with OS prevalence. CONCLUSION: This is the first study to estimate the prevalence of IBS, FD, and their OS and assess the behavioral and demographic risk factors associated with these disorders in the Bulgarian population. Our results are valuable in filling in the epidemiological data gap regarding IBS, FD, and OS in Eastern Europe.