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Effect of pulsed corticosteroids and tocilizumab on hyperinflammation in COVID-19 patients with acute respiratory distress syndrome

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Journal of Acute Disease 2021年第5期10卷 195-201页

作者： Murat Aslan Mehmet Süleyman Sabaz Rabia Yilmaz Sinan Aşar Yasemin TekdöşŞeker Gülsüm Oya Hergünsel Health Sciences University Bakırköy Dr Sadi Konuk Training and Research HospitalAnesthesia and Reanimation ClinicIstanbulTurkey Marmara University Pendik Training and Research Hospital Anesthesia and Reanimation ClinicIstanbulTurkey

Objective:To compare the efficacy of pulsed-dose corticosteroids(≥250 mg methylprednisolone,3 days)and tocilizumab in treating COVID-19-related ***:This prospective observational study included RT-PCR positive COVID-19 patients with acute respiratory distress syndrome,who were admitted to the COVID-19 Adult Intensive Care Unit of Prof *** Dilmener Emergency Hospital(Istanbul,Turkey)between December 1,2020 and February 28,***,laboratory and radiological examinations were used to diagnose COVID-19 associated *** cohort groups were formed:the pulsed-dose corticosteroids group(250 mg methylprednisolone for 3 days),the tocilizumab group(8 mg/day single dose or 400 mg/day for 2 days),and the combined group(pulsed-dose corticosteroid+tocilizumab).The difference in mortality rates among the groups was compared *** most common cause(s)of death was ***,adverse events(secondary infection,acute kidney injury,arrhythmia,gastrointestinal system bleeding)for 28 days were ***:A total of 60 patients were included in this study,with 20 patients in each *** was no statistically significant difference between the 3 groups in mortality rates(55%in the pulsed corticosteroid group,60%in the tocilizumab group,50%in the combined group,χ2=0.404,P=0.817).Infectious causes were found to be the most common cause of mortality in all the three groups,and no difference was found between them(χ2=0.404,P=0.817).There was also no difference in the development of adverse events such as secondary infection,acute kidney injury,arrhythmia,and gastrointestinal bleeding among the groups(P>0.05).Conclusions:Corticosteroids can be used instead of tocilizumab to treat hyperinflammation in COVID-19 patients with acute respiratory distress syndrome.

关键词： COVID-19 Acute respiratory distress syndrome hyperinflammation Pulse dose steroid Tocilizumab

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The Cell Biology of Systemic hyperinflammation Resulting from Failed Cytolytic Target Cell Killing

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CellBio 2015年第3期4卷 37-45页

作者： Bor Luen Tang Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore

Mutations in genes encoding a key component of cytotoxic granules, or the machinery for their release, underlie the systemic hyperiflammatory symptoms of familial hemophagocytic lymphohistiocytosis (FHL), a typically pediatric onset autosomal recessive disorder with five known genetic subtypes (FHL1 - 5). FHL1 mutations have been mapped to chromosome 9, while the respective genes mutated in FHL2 (PRF1), FHL3 (UNC13D/Munc13-4), FHL4 (STX11) and FHL5 (STXBP2/ Munc18b/Munc18-2) have been identified. Perforin gene mutation directly affected the cytolytic activity of the cytotoxic granules. All the other FHL mutations appear to affect some aspect of cytotoxic granule exocytosis, resulting in impaired target cell killing by cytolytic T lymphocytes (CTLs) and/or natural killer (NK) cells. Recent findings suggest that failure to kill and detach from target cells, and prolonged synapse connection time, promote cytokine hypersecretion by the defective CTLs and NKs, which in turn result in systemic inflammation. Deciphering the genetics of FHL has contributed towards our understanding of the cell biology of hyperinflammatory responses and hemophagocytic lymphohistiocytosis accompanying pathological conditions such as cancer and viral infections.

关键词： Cytokine Storms Cytolytic T Lymphocytes (CTLs) Familial Hemophagocytic Lymphohistiocytosis (FHL) Natural Killer (NK) Cells hyperinflammation

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Molecular mechanisms implicated in SARS-CoV-2 liver tropism

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World Journal of Gastroenterology 2022年第48期28卷 6875-6887页

作者： Jorge Quarleri M.Victoria Delpino Institute for Biomedical Research on Retroviruses and AIDS Faculty of Medical SciencesNational Scientific and Technical Research Council-University of Buenos AiresBuenos Aires 1121Argentina

The coronavirus disease 2019(COVID-19)pandemic is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Hepatic involvement is common in SARS-CoV-2-infected *** is currently accepted that the direct and indirect hepatic effects of SARS-CoV-2 infection play a significant role in *** individuals with pre-existing infectious and non-infectious liver disease,who are at a remarkably higher risk of developing severe COVID-19 and death,this pathology is most medically *** review emphasizes the current pathways regarded as contributing to the gastrointestinal and hepatic ailments linked to COVID-19-infected patients due to an imbalanced interaction among the liver,systemic inflammation,disrupted coagulation,and the lung.

关键词： SARS-CoV-2 Viral hepatitis Non-infectious liver disease hyperinflammation Coronavirus disease 2019

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SARS-CoV-2 spike protein as a bacterial lipopolysaccharide delivery system in an overzealous inflammatory cascade

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Journal of Molecular Cell Biology 2022年第9期14卷 26-39页

作者： Firdaus Samsudin Palur Raghuvamsi Ganna Petruk Manoj Puthia Jitka Petrlova Paul MacAry Ganesh S.Anand Peter J.Bond Artur Schmidtchen Bioinformatics Institute(BIl) Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Department of Biological Sciences National University of SingaporeSingapore 117543Singapore Division of Dermatology and Venereology Department of Clinical SciencesLund UniversitySE-22184 LundSweden Life Sciences Institute Centre for Life SciencesNational University of SingaporeSingapore 117546Singapore Department of Chemistry The Pennsylvania State UniversityPA 16801USA Copenhagen Wound Healing Center Bispebjerg HospitalDepartment of Biomedical SciencesUniversity of CopenhagenDK-2400 CopenhagenDenmark

Accumulating evidence indicates a potential role for bacterial lipopolysaccharide(LPs)in the overactivation of the immune response during SARS-CoV-2 *** is recognized by Toll-like receptor 4,mediating proinflammatory *** previously reported that LPS directly interacts with SARS-CoV-2 spike(S)protein and enhances proinflammatory *** native gel electrophoresis and hydrogen-deuterium exchange mass spectrometry,we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the S *** simulations validated by a microscale thermophoresis binding assay revealed that LPS binds to the S2 pocket with a lower affinity compared to S1,suggesting a role as an intermediate in LPS ***,nuclear factor-kappa B(NF-kB)activation in monocytic THP-1 cells is strongly boosted by *** NF-kB reporter mice followed by bioimaging,a boosting effect was observed for both S1 and S2,with the former potentially facilitated by *** Omicron S variant binds to LPS,but with reduced affinity and LPS boosting in vitro and in *** together,the data provide a molecular mechanism by which S protein augments LPS-mediated hyperinflammation.

关键词： COVID-19 SARS-CoV-2 spike protein lipopolysaccharide TLR4 hyperinflammation

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Pregnancy・lnduced Hemophagocytic Lymphohistiocytosis: A Case Report and Literature Review

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Chinese Medical Sciences Journal 2020年第4期35卷 371-376页

作者： Jie Zhao Yimeng Yang Shuhong Ming Department of Medical Oncology State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Department of Respiratory and Critical Care Medicine Beijing HospitalBeijing 100730China

Hemophagocytic lymphohistiocytosis(HLH)is a rare but devastating disease characterized by dysregulated immune response and hyp er *** our knowledge,pregnancy-induced HLH has been rarely reported in the literature.A 30-year・old pregnant woman presented persistent fever for 21 days since 17 weeks of *** possible etiologies such as infection,autoimmune disorder,and malignancy had been ruled out based on a series of exhaustive *** disease progressed despite the use of broadspectrum antibiotics and *** patient was diagnosed as pregnancy-induced HLH,and finally recovered completely after termination of pregnancy by caesarean and the continuous use of glucocorticoid which played a crucial part in controlling hyp er ***-induced HLH could be fatal if effective treatment was not initiated *** studies are needed to improve early diagnosis and etiology identification of HLH.

关键词： hemophagocytosis hyperinflammation pregnancy

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