Gastrointestinal symptoms in COVID-19 and disease severity: a Japanese registry-based retrospective cohort study.

BACKGROUND: Research on whether gastrointestinal symptoms correlate with the severity of Coronavirus Disease 2019 (COVID-19) has been inconclusive. This study aimed to clarify any associations between gastrointestinal symptoms and the prognosis of COVID-19. METHODS: We collected data from the Japanese nationwide registry for COVID-19 to conduct a retrospective cohort study. Data from 3498 Japanese COVID-19 patients, diagnosed at 74 facilities between February 2020 and August 2022, were analyzed in this study. Hospitalized patients were followed up until discharge or transfer to another hospital. Outpatients were observed until the end of treatment. Associations between gastrointestinal symptoms and clinical outcomes were investigated using multivariable-adjusted logistic regression models. RESULTS: The prevalence of diarrhea, nausea/vomiting, abdominal pain, and melena were 16.6% (581/3498), 8.9% (311/3498), 3.5% (121/3498), and 0.7% (23/3498), respectively. In the univariable analysis, admission to intensive care unit (ICU) and requirement for mechanical ventilation were less common in patients with diarrhea than those without (ICU, 15.7% vs. 20.6% (p = 0.006); mechanical ventilation, 7.9% vs. 11.4% (p = 0.013)). In the multivariable-adjusted analysis, diarrhea was associated with lower likelihood of ICU admission (adjusted odds ratio (aOR), 0.70; 95% confidence interval (CI), 0.53-0.92) and mechanical ventilation (aOR, 0.61; 95% CI, 0.42-0.89). Similar results were obtained in a sensitivity analysis with another logistic regression model that adjusted for 14 possible covariates with diarrhea (ICU; aOR, 0.70; 95% CI, 0.53-0.93; mechanical ventilation; aOR 0.62; 95% CI, 0.42-0.92). CONCLUSIONS: Diarrhea was associated with better clinical outcomes in COVID-19 patients.

Draft Genome Sequence of Streptomyces sp. Strain G-5, Isolated from Marine Sponge, Kochi Prefecture, Japan.

Actinomycetes isolated from the marine environment often require the presence of seawater for their growth and/or morphological development. Here, we report the isolation and genome sequencing of marine sponge-derived Streptomyces sp. strain G-5 with such a seawater requirement.

Enrichment of type I interferon signaling in colonic group 2 innate lymphoid cells in experimental colitis.

Group 2 innate lymphoid cells (ILC2s) serve as frontline defenses against parasites. However, excluding helminth infections, it is poorly understood how ILC2s function in intestinal inflammation, including inflammatory bowel disease. Here, we analyzed the global gene expression of ILC2s in healthy and colitic conditions and revealed that type I interferon (T1IFN)-stimulated genes were up-regulated in ILC2s in dextran sodium sulfate (DSS)-induced colitis. The enhancement of T1IFN signaling in ILC2s in DSS-induced colitis was correlated with the downregulation of cytokine production by ILC2s, such as interleukin-5. Blocking T1IFN signaling during colitis resulted in exaggeration of colitis in both wild-type and Rag2-deficient mice. The exacerbation of colitis induced by neutralization of T1IFN signaling was accompanied by reduction of amphiregulin (AREG) in ILC2s and was partially rescued by exogenous AREG treatment. Collectively, these findings show the potential roles of T1IFN in ILC2s that contribute to colitis manifestation.

DOCK2 is involved in the host genetics and biology of severe COVID-19.

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1-5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Integration of Hot Tube Gas Forming and Die Quenching of Ultra-High Strength Steel Hollow Parts Using Low Pressure Sealed-Air.

A low pressure sealed-air hot tube gas forming process of ultra-high strength steel tubes was developed not only to change the cross-section of the hollow products by bulging but also to increase the strength of components. Gas-formed components are typically formed by a controlled-gas pressure with extremely high internal pressure, which leads to affected production costs and safety. Moreover, compressing the gas with high pressure requires high energy during its preparation. Therefore, to simplify the internal pressure controlling system and improve the safety factor in gas forming processes, the sealed-air tubes are formed with a quite low initial pressure. The pressure of the sealed air increased with increasing temperature of the air inside the resistance-heated tube, and the bulging deformation was controlled only by axial feeding. The effects of the initial pressure and heating temperature on the bulging deformation and quenchability of the tubes, and the effect of the starting time of axial feeding on the bulging behavior were examined. Consequently, ultra-high strength steel bulged parts were produced even in low initial internal pressure and with the rapid heating of the tubes.

Organ and brain crosstalk: The liver-brain axis in gastrointestinal, liver, and pancreatic diseases.

The liver is the largest organ in the human body and is responsible for the metabolism and storage of the three principal nutrients: carbohydrates, fats, and proteins. In addition, the liver contributes to the breakdown and excretion of alcohol, medicinal agents, and toxic substances and the production and secretion of bile. In addition to its role as a metabolic centre, the liver has recently attracted attention for its function in the liver-brain axis, which interacts closely with the central nervous system via the autonomic nervous system, including the vagus nerve. The liver-brain axis influences the control of eating behaviour in the central nervous system through stimuli from the liver. Conversely, neural signals from the central nervous system influence glucose, lipid, and protein metabolism in the liver. The liver also receives a constant influx of nutrients and hormones from the intestinal tract and compounds of bacterial origin via the portal system. As a result, the intestinal tract and liver are involved in various immunological interactions. A good example is the co-occurrence of primary sclerosing cholangitis and ulcerative colitis. These heterogeneous roles of the liver-brain axis are mediated via the vagus nerve in an asymmetrical manner. In this review, we provide an overview of these interactions, mainly with the liver but also with the brain and gut.