Objective: Coronavirus disease 2019 (COVID‐19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID‐19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID‐19 patients was lacking.Methods: 325 patients with laboratory‐confirmed critical COVID‐19 were enrolled from 4 government‐designated COVID‐19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28‐ and 60‐day mortality, and the secondary outcomes were the total length of in‐hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID‐19, IVIG dosage and timing.Results: In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28‐day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in‐hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28‐day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60‐day mortality in the critical‐type patients.Conclusion: Early administration of IVIG with high dose improves the prognosis of critical‐type patients with COVID‐19. This study provides important information on clinical application of IVIG in the treatment of SARS‐CoV‐2 infection, including patient selection and administration dosage and timing.

Dysfunction of the intestinal epithelial tight junction (TJ) barrier is known to have an important etiologic role in the pathophysiology of heat stroke. N-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in maintaining and protecting the TJ structure and function. This study is aimed at investigating whether n-3 PUFAs could alleviate heat stress-induced dysfunction of intestinal tight junction. Human intestinal epithelial Caco-2 cells were pre-incubated with EPA, DHA or arachidonic acid (AA) and then exposed to heat stress. Transepithelial electrical resistance (TEER) and Horseradish Peroxidase (HRP) permeability were measured to analyze barrier integrity. Levels of TJ proteins, including occludin, ZO-1 and claudin-2, were analyzed by Western blot and localized by immunofluorescence microscopy. Messenger RNA levels were determined by quantitative real time polymerase chain reaction (Q-PCR). TJ morphology was observed by transmission electron microscopy. EPA effectively attenuated the decrease in TEER and impairment of intestinal permeability in HRP flux induced by heat exposure. EPA significantly elevated the expression of occludin and ZO-1, while DHA was less effective and AA was not at all effective. The distortion and redistribution of TJ proteins, and disruption of morphology were also effectively prevented by pretreatment with EPA. This study indicates for the first time that EPA is more potent than DHA in protecting against heat-induced permeability dysfunction and epithelial barrier damage of tight junction.

This study aimed to investigate the possible effect of omega-3 fatty acids on reducing the mortality of sepsis and sepsis-induced acute respiratory distress syndrome (ARDS) in adults. Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, WangFang database, and Chinese BioMedical Literature Database from their inception to March 6, 2017, were searched using systematic review researching methods. Five factors were analyzed to investigate the correlation between omega-3 fatty acids (either parenteral or enteral supplementation) and mortality rate. Forty randomized controlled trials (RCTs) were initially included, but only 25 of them assessed mortality. Of these RCTs, nine used enteral nutrition (EN) and 16 used parenteral nutrition (PN). The total mortality rate in the omega-3 fatty acid group was lower than that in the control group. However, the odds ratio (OR) value was not significantly different in the EN or PN subgroup. Eighteen RCTs including 1790 patients with similar severity of sepsis and ARDS were also analyzed. The OR value was not significantly different in the EN or PN subgroup. Omega-3 fatty acids did not show positive effect on improving mortality of sepsis-induced ARDS (p = 0.39). But in EN subgroup, omega-3 fatty acids treatment seemed to have some benefits in reducing mortality rate (p = 0.04). In the RCTs including similar baseline patients, partial correlation analysis found that the concentration ratio of n-6 to n-3 fatty acids had positive correlation with reduction of mortality (RM) (γ = 0.60, P = 0.02), whereas the total number of each RCT had negative correlation with RM (γ = − 0.54, P = 0.05). This review found that omega-3 fatty acid supplementation could reduce the mortality rate of sepsis and sepsis-induced ARDS. However, further investigation based on suitable concentrations and indications is needed to support the findings.

Purpose: Rhabdomyolysis (RM) has been associated with many viral infectious diseases, and associated with poor outcomes. We aim to evaluate the clinical features and outcomes of RM in patients with coronavirus disease 2019 (COVID-19). Method: This was a single-center, retrospective, cohort study of 1,014 consecutive hospitalized patients with confirmed COVID-19 at the Huoshenshan Hospital in Wuhan, China, between February 17 and April 12, 2020. Results: The overall incidence of RM was 2.2%. Compared with patients without RM, those with RM tended to have a higher risk of deterioration. Patients with RM also constituted a greater percentage of patients admitted to the intensive care unit (90.9% vs. 5.3%, P < 0.001) and a greater percentage of patients undergoing mechanical ventilation (86.4% vs. 2.7% P < 0.001). Moreover, patients with RM had laboratory test abnormalities, including the presence of markers of inflammation, activation of coagulation, and kidney injury. Patients with RM also had a higher risk of in-hospital death (P < 0.001). Cox's proportional hazard regression model analysis confirmed that RM indicators, including peak creatine kinase levels > 1,000 IU/L (HR = 6.46, 95% CI: 3.02–13.86) and peak serum myoglobin concentrations > 1,000 ng/mL (HR = 9.85, 95% CI: 5.04–19.28), were independent risk factors for in-hospital death. Additionally, patients with COVID-19 that developed RM tended to have delayed viral clearance. Conclusion: RM might be an important contributing factor to adverse outcomes in COVID-19 patients. The early detection and effective intervention of RM may help reduce mortality among COVID-19 patients.

Heat stress and gut‑derived endotoxinemia are common causes of multiple organ dysfunction syndrome in heat stroke patients. Evidence has demonstrated that cell apoptosis in the small intestine serves an important role in the pathogenesis of heatstroke, which leads to increased intestinal permeability to endotoxin or lipopolysaccharides (LPS) from the gut entering the circulation. However, little is known about the potential underlying mechanisms mediating heat stress combined with LPS‑induced intestinal epithelial cell apoptosis. In the present study, LPS combined with heat stress induced production of reactive oxygen species (ROS), mitochondrial membrane potential disruption and cell apoptosis, which eventually led to increased intestinal permeability and reduced epithelial resistance in the IEC‑6 cell line. Inductions in ROS, mitochondrial membrane potential disruption and cell apoptosis were detected by using an ROS assay kit, 5,5',6,6'‑tetrachloro‑1,1',3,3'tetraethylbenzimidazo carbocyanine iodide dye kit and annexin V‑fluorescein isothiocyanate apoptosis kit, respectively. The effect of ROS on mitogen activated protein kinases (MAPKs) and c‑Jun activation was investigated using the antioxidant drug, butylated hydroxyanisole (BHA) by western blotting. The results of the present study demonstrated that ROS is essential to activate p38, extracellular signal‑regulated kinase (ERK) and c‑Jun, but not c‑Jun N‑terminal kinase (JNK), in LPS combined with heat stress treated cells. Furthermore, ROS, and activation of p38, JNK and c‑Jun, were revealed to serve pro‑apoptosis roles which aggravated damage to epithelial barrier integrity, as assessed by flow cytometry using Annexin V‑fluorescein isothiocyanate staining and pretreatment of cells with specific inhibitors of ROS, JNK, p38 and c‑Jun (BHA, SP600125, SB203580 and c‑Jun peptide, respectively). Transepithelial electrical resistance and horseradish peroxidase permeability were detected in cells treated with LPS combined with heat stress, which revealed that ERK serves an anti‑apoptosis role, as determined by pretreatment of cells with PD98059, a specific inhibitor of ERK. In conclusion, these findings suggested a novel role of the ROS signaling pathway which involved activation of MAPKs and c‑Jun, following LPS combined with heat stress‑induced IEC‑6 cell apoptosis and impairment of the epithelial barrier. These results may facilitate understanding of pathological conditions involving ROS, such as heat stroke.