Clinical observation of glucocorticoid therapy for critically ill patients with COVID-19 pneumonia.

OBJECTIVE: We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. METHODS: Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. RESULTS: There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. CONCLUSION: In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.

Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells.

Purpose: The purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells. Methods: The expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay. Results: ACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme. Conclusions: In this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.

Immune response to intravenous immunoglobulin in patients with Kawasaki disease and MIS-C.

BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1ß have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1ß. Following IVIG treatment, activated IL-1ß+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1ß can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation.

Age-dependent regulation of SARS-CoV-2 cell entry genes and cell death programs correlates with COVID-19 severity.

Novel coronavirus disease 2019 (COVID-19) severity is highly variable, with pediatric patients typically experiencing less severe infection than adults and especially the elderly. The basis for this difference is unclear. We find that mRNA and protein expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, increases with advancing age in distal lung epithelial cells. However, in humans, ACE2 expression exhibits high levels of intra- and interindividual heterogeneity. Further, cells infected with SARS-CoV-2 experience endoplasmic reticulum stress, triggering an unfolded protein response and caspase-mediated apoptosis, a natural host defense system that halts virion production. Apoptosis of infected cells can be selectively induced by treatment with apoptosis-modulating BH3 mimetic drugs. Notably, epithelial cells within young lungs and airways are more primed to undergo apoptosis than those in adults, which may naturally hinder virion production and support milder COVID-19 severity.

Evaluation of organ function in patients with severe COVID-19 infections.

OBJECTIVE: The purpose of our study was to assess organ function in 102 patients with severe COVID-19 infections, using retrospective clinical analysis. MATERIAL AND METHODS: A retrospective analysis was conducted on 102 patients with severe COVID-19 infections. The patients were divided into a survival group (n=73) and a non-survival group (n=29) according to their prognosis. The age, sex, underlying diseases, clinical laboratory data within 48h (routine blood tests, ALT, AST, TBIL, ALB, BUN, CR, D-Dimer, PT, APTT, FIB, F VIII:C, CK-MB, CK, and LDH), and ventilation status were collected. The organ functions of these severe COVID-19 patients were assessed by comparing the differences between the two groups. RESULTS: AST, BUN, CR, CK-MB, LDH, and CK in the non-survival group were higher than those in the survival group, and the differences were statistically significant (P<0.05). D-Dimer, PT, FIB, and F VIII:C in the non-survival group were higher than the values observed in the survival group, and the differences were statistically significant (P<0.05). PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH predicted the area under the ROC curve (AUC) of the COVID19 endpoint events and were 0.721, 0.854, 0.867, 0.757, 0.699, 0.679, 0.715, 0.811, 0.935, and 0.802, respectively. CONCLUSION: The results showed that there were different degrees of damage to the liver, kidneys, blood coagulation, and heart function in the non-survival group. In addition, PLT, AST, BUN, CR, D-Dimer, PT, FIB, F VIII:C, CK-MB, CK, and LDH had value in evaluating disease prognosis.