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host protection against Omicron BA.2.2 sublineages by prior vaccination in spring 2022 COVID-19 outbreak in Shanghai

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Frontiers of Medicine 2023年第3期17卷 562-575页

作者： Ziyu Fu Dongguo Liang Wei Zhang Dongling Shi Yuhua Ma Dong Wei Junxiang Xi Sizhe Yang Xiaoguang Xu Di Tian Zhaoqing Zhu Mingquan Guo Lu Jiang Shuting Yu Shuai Wang Fangyin Jiang Yun Ling Shengyue Wang Saijuan Chen Feng Liu Yun Tan Xiaohong Fan Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University(SJTU)School of MedicineShanghai 200025China National Translational Science Center for Molecular Medicine&Department of Cell Biology Fourth Military Medical UniversityXi’an 710032China Shanghai Public Health Clinical Center Fudan UniversityShanghai 201508China Department of Nephrology Traditional Chinese Medicine Hospital of KunShanSuzhou 215300China Department of Infectious Diseases Ruijin Hospital Affiliated to Shanghai Jiao Tong University(SJTU)School of MedicineShanghai 200025China

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic.Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022.Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020,BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood.In particular,severe/critical cases of COVID19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment.Importantly,the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototypeinactivated vaccines,supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records.Furthermore,even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection,vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged≥60 years old.Together,our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.

关键词： SARS-CoV-2 COVID-19 host response bronchoalveolar lavage fluid(BALF)

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Sepsis heterogeneity

World Journal of Pediatrics 2023年第10期19卷 919-927页

作者： Wei Wang Chun-Feng Liu Department of Pediatrics ShengJing Hospital of China Medical UniversityNo.36SanHao StreetShenyang CityLiaoning Province 110004China

Background Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with extremely high mortality.Notably,sepsis is a heterogeneous syndrome characterized by a vast,multidimensional array of clinical and biologic features,which has hindered advances in the therapeutic field beyond the current standards.Data sources We used PubMed to search the subject-related medical literature by searching for the following single and/or combination keywords:sepsis,heterogeneity,personalized treatment,host response,infection,epidemiology,mortality,incidence,age,children,sex,comorbidities,gene susceptibility,infection sites,bacteria,fungi,virus,host response,organ dysfunction and management.Results We found that host factors(age,biological sex,comorbidities,and genetics),infection etiology,host response dysregulation and multiple organ dysfunctions can all result in different disease manifestations,progression,and response to treatment,which make it difficult to effectively treat and manage sepsis patients.Conclusions Herein,we have summarized contributing factors to sepsis heterogeneity,including host factors,infection etiology,host response dysregulation,and multiple organ dysfunctions,from the key elements of pathogenesis of sepsis.An in-depth understanding of the factors that contribute to the heterogeneity of sepsis will help clinicians understand the complexity of sepsis and enable researchers to conduct more personalized clinical studies for homogenous patients.

关键词： Heterogeneity host response Infection Personalized treatment Sepsis

Biocompatibility pathways and mechanisms for bioactive materials:The bioactivity zone

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Bioactive Materials 2022年第4期7卷 306-322页

作者： David F.Williams Wake Forest Institute of Regenerative Medicine 391 Technology Way.Winston-SalemNorth Carolina27101USA

This essay analyzes the scientific evidence that forms the basis of bioactive materials,covering the fundamental understanding of bioactivity phenomena and correlation with the mechanisms of biocompatibility of biomaterials.This is a detailed assessment of performance in areas such as bone-induction,cell adhesion,immunomodulation,thrombogenicity and antimicrobial behavior.Bioactivity is the modulation of biological activity by characteristics of the interfacial region that incorporates the material surface and the immediate local host tissue.Although the term‘bioactive material’is widely used and has a well understood general meaning,it would be useful now to concentrate on this interfacial region,considered as‘the bioactivity zone’.Bioactivity phenomena are either due to topographical/micromechanical characteristics,or to biologically active species that are presented in the bioactivity zone.Examples of topographical/micromechanical effects are the modulation of the osteoblast-osteoclast balance,nanotopographical regulation of cell adhesion,and bactericidal nanostructures.Regulation of bioactivity by biologically active species include their influence,especially of metal ions,on signaling pathways in bone formation,the role of cell adhesion molecules and bioactive peptides in cell attachment,macrophage polarization by immunoregulatory molecules and antimicrobial peptides.While much experimental data exists to demonstrate the potential of such phenomena,there are considerable barriers to their effective clinical translation.This essay shows that there is solid scientific evidence of the existence of bioactivity mechanisms that are associated with some types of biomaterials,especially when the material is modified in a manner designed to specifically induce that activity.

关键词： Bioactivity host response Biomaterial Medical technology Cell signaling

Immunosenescence Accelerates Disease Progression and Elevates host response in Aged Chinese Rhesus Macaques Infected with SIVmac239

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Immunosenescence Accelerates Disease Progression and Elevate...

Inducible Rubicon facilitates viral replication by antagonizing interferon production

第十一届全国免疫学学术大会

作者： Zheng Hong-Yi Zhang Ming-Xu Chen Min Pang Wei Zhang Gao-Hong Zheng Yong-Tang Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences& Yunnan Province Kunming Institute of ZoologyChinese Academy of Sciences

Objective: Elderly HIV patients usually have a slower rate of immune reconstitution and a higher risk of mortality and AIDS progression than adult patients. Immunosenescence may primarily lead to these unsatisfactory clinical outcomes. However, this hypothesis is still not fully tested as lacking appropriate animal models for the elderly AIDS. We constructed the aged Chinese rhesus macaque(Ch RM) AIDS models to find the characteristics of elderly AIDS and explore the mechanisms of elderly AIDS. Methods: We intensively compared the immunological, virological and gene-expressed dynamics between 6 young(mean age = 7) and 12 old(mean age = 18) Ch RM throughout the early SIVmac239 infection(3 months post infection). Results: After 42 days post infection, 4 old Ch RM gradually died of AIDS complications. Old Ch RM showed a faster AIDS development than young macaques as their rapidly elevated plasma viral load, fast loss of CD4 T cells and serious inversion of CD4/CD8 ratio during acute infection. The low frequency of naive CD4 T cells prior to infection and the violent proliferation of naive lymphocytes after infection strongly predicted increased disease progression, which suggested that naive T cells play an important role in immune protection during early SIV infection and old Ch RM have lost control of disease progression as their less naive lymphocytes. Moreover, a robust host response with defective regulation in old Ch RM was associated with rapidly elevated homeostatic proliferation and loss of naive CD4 T cells. This phenomenon partially delayed the depletion of naive CD4 T cells, but in fact enhanced the immune activation and inflammation and accelerated disease progression of hosts. Conclusion: Overall, we demonstrated that SIV-infected old Ch RM may be a favorable model for the pathogenesis research of elderly AIDS and the therapeutic strategies of elderly AIDS should focus on the reverse of immunosenescence and the effective control of abnormal immune response.

关键词： aged animal AIDS model Chinese rhesus macaque immunosenescence host response SIV infection

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Cellular & Molecular Immunology 2017年第7期14卷 607-620页

作者： Yushun Wan Wei Cao Tao Han Sheng Ren Jian Feng TieLong Chen Jun Wang Ruth Broering Mengji Lu Ying Zhu State Key Laboratory of Virology and College of Life Sciences Wuhan UniversityWuhan 430072China Department of Infectious Diseases Zhongnan Hospital of Wuhan UniversityWuhan 430072China Medical Faculty Department of Gastroenterology and HepatologyUniversity of Duisburg-EssenEssen 45127Germany Institute of Virology University of Duisburg-EssenEssen 45127Germany

The RUN domain Beclin-1-interacting cysteine-rich-containing(Rubicon)protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner,but little is known regarding the role of Rubicon during viral infection.Here,we performed functional studies of the identified target in interferon(IFN)signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN.The Rubicon protein levels were elevated in peripheral blood mononuclear cells,sera and liver tissues from patients with hepatitis B virus(HBV)infection relative to those in healthy individuals.Assays of the overexpression and knockdown of Rubicon showed that Rubicon significantly promoted HBV replication.In addition,Rubicon knockdown resulted in the inhibition of enterovirus 71,influenza A virus and vesicular stomatitis virus.The expression o0f Rubicon led to the suppression of virus-induced type-I interferon(IFN-αand IFN-β)and type-III interferon(IFN-λ1).Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process,and the NF-κB essential modulator(NEMO),a key factor in the IFN pathway,was the target with which Rubicon interacted.Our results reveal a previously unrecognized function of Rubicon as a virus-induced protein that binds to NEMO,leading to the inhibition of type-I interferon production.Rubicon thus functions as an important negative regulator of the innate immune response,enhances viral replication and may play a role in viral immune evasion.

关键词： host response immune evasion interferon Rubicon viral infection

Comparison of clinical laboratory tests between bacterial sepsis and SARS-CoV-2-associated viral sepsis

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Military Medical Research 2021年第2期8卷 278-280页

作者： Chao Ren Ren-Qi Yao Di Ren Ying Li Yong-Wen Feng Yong-Ming Yao Department of Critical Care Medicine the Second People’s Hospital of ShenzhenShenzhen 518035GuangdongChina Department of Critical Care Medicine the Third People’s Hospital of ShenzhenShenzhen 518020GuangdongChina Trauma Research Center the Fourth Medical Center and Medical Innovation Research Department of the Chinese PLA General HospitalBeijing 100048China

Sepsis is a life-threatening condition that is characterized by multiple organ dysfunction due to abnormal host response to various pathogens,like bacteria,fungi and virus.The differences between viral and bacterial sepsis are indeed of great significance to deepen the understanding of the pathogenesis of sepsis,especially under pandemics of SARS-CoV-2 infection.

关键词： Severe acute respiratory syndrom coronavirus 2 Coronavirus disease 2019 Sepsis Bacteria Virus Infection host response

An overview of the role of neutrophils in innate immunity,inflammation and host-biomaterial integration

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Regenerative Biomaterials 2017年第1期4卷 55-68页

作者： Gretchen S.Selders Allison E.Fetz Marko Z.Radic Gary L.Bowlin Department of Biomedical Engineering University of MemphisMemphisTNUSA Department of Microbiology Immunology and BiochemistryUniversity of Tennessee Health Science Center(UTHSC)MemphisTN 38163USA

Despite considerable recent progress in defining neutrophil functions and behaviors in tissue repair,much remains to be determined with regards to its overall role in the tissue integration of biomaterials.This article provides an overview of the neutrophil’s numerous,important roles in both inflammation and resolution,and subsequently,their role in biomaterial integration.Neutrophils function in three primary capacities:generation of oxidative bursts,release of granules and formation of neutrophil extracellular traps(NETs);these combined functions enable neutrophil involvement in inflammation,macrophage recruitment,M2 macrophage differentiation,resolution of inflammation,angiogenesis,tumor formation and immune system activation.Neutrophils exhibit great flexibility to adjust to the prevalent microenvironmental conditions in the tissue;thus,the biomaterial composition and fabrication will potentially influence neutrophil behavior following confrontation.This review serves to highlight the neutrophil’s plasticity,reiterating that neutrophils are not just simple suicidal killers,but the true maestros of resolution and regeneration.

关键词： neutrophil tissue engineering NETosis tissue regeneration host response inflammation

Neosporosis: An Overview of Its Molecular Epidemiology and Pathogenesis

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Engineering 2020年第1期6卷 10-19页

作者： Asis Khan Jahangheer S.Shaik Patricia Sikorski Jitender P.Dubey Michael E.Grigg Molecular Parasitology Section Laboratory of Parasitic DiseasesNational Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaMD 20892USA Animal Parasitic Disease Laboratory Beltsville Agricultural Research CenterAgricultural Research ServiceUS Department of AgricultureBeltsvilleMD 20705USA

Neospora caninum (N. caninum), a cyst-forming protozoan parasite, is a major cause of bovine abortions and neonatal mortality worldwide. N. caninum has a broad intermediate host range, and its sexual cycle occurs exclusively in canids. Another species of Neospora, Neospora hughesi (N. hughesi), has been identified and causes myeloencephalitis in horses. Although molecular epidemiology studies are in their infancy, the 18S ribosomal RNA (rRNA) and ITS1 regions within the small subunit ribosomal RNA (ssuRNA) and an N. caninum species-specific DNA probe (pNc5) have been used extensively to differentiate Neospora from other closely related apicomplexan parasites. While these repetitive regions have higher sensitivity and specificity than housekeeping or antigen genes, they suffer from low discriminatory power and fail to capture intra-species diversity. Similarly, although multiple minisatellite or microsatellite marker studies have shown clear geographic substructures within Neospora, strains are often misclassified due to a convergence in the size of different alleles at microsatellite loci, known as homoplasy. Only one strain, N. caninum Liverpool (Nc-Liv), has been genome sequenced and compared with its closest relative, Toxoplasma gondii (T. gondii). Hence, detailed population genomics studies based on whole-genome sequences from multiple strains worldwide are needed in order to better understand the current population genetic structure of Neospora, and ultimately to determine more effective vaccine candidates against bovine neosporosis. The aim of this review is to outline our current understanding of the molecular epidemiology and genomics of Neospora in juxtaposition with the closely related apicomplexan parasites Hammondia hammondi and T. gondii.

关键词： Neosporosis Molecular epidemiology Population genetics Genomics host response Vaccine

Siblings with coronavirus disease 2019 infection and opposite outcome—the hemodialysis’s better outcome paradox:Two case reports

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World Journal of Nephrology 2021年第2期10卷 21-28页

作者： Dimitra Bacharaki Evangelia Chrysanthopoulou Sotiria Grigoropoulou Panagiotis Giannakopoulos Panagiotis Simitsis Frantzeska Frantzeskaki Aikaterini Flevari Minas Karagiannis Aggeliki Sardeli DimitraKavatha Anastasia Antoniadou Demetrios Vlahakos Department of Nephrology B Propaideutiki Internal Medicine ClinicAttikon University HospitalChaidari 12064Greece Intensive Care Unit Attikon University HospitalChaidari 12064Greece D Internal Medicine Clinic Attikon University HospitalChaidari 12064Greece

BACKGROUND Coronavirus disease 2019(COVID-19)is a highly contagious infection caused by the severe acute respiratory syndrome coronavirus 2 virus and has a unique underlying pathogenesis.Hemodialysis(HD)patients experience high risk of contamination with COVID-19 and are considered to have higher mortality rates than the general population by most but not all clinical series.We aim to highlight the peculiarities in the immune state of HD patients,who seem to have both immune-activation and immune-depression affecting their outcome in COVID-19 infection.CASE SUMMARY We report the opposite clinical outcomes(nearly asymptomatic course vs death)of two diabetic elderly patients infected simultaneously by COVID-19,one being on chronic HD and the other with normal renal function.They were both admitted in our hospital with COVID-19 symptoms and received the same treatment by protocol.The non-HD sibling deteriorated rapidly and was intubated and transferred to the Intensive Care Unit,where he died despite all supportive care.The HD sibling,although considered more“high-risk”for adverse outcome,followed a benign course and left the hospital alive and well.CONCLUSION These cases may shed light on aspects of the immune responses to COVID-19 between HD and non-HD patients and stimulate further research in pathophysiology and treatment of this dreadful disease.

关键词： Case report Hemodialysis Siblings COVID-19 host response Immuneactivation Immune-depression