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Nasal vaccination of triple-RBD scaffold protein with flagellin elicits long-term protection against SARS-CoV-2 variants including JN.1

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2312-2323页

作者： Xian Li Mengxin Xu Jingyi Yang Li Zhou Lin Liu Min Li Shasha Wang Mei-Qin Liu Zhixiang Huang Zhen Zhang Shuning Liu Yunqi Hu Haofeng Lin Bowen Liu Ying Sun Qingguo Wu Zheng-Li Shi Ke Lan Yu Chen Huimin Yan Yao-Qing Chen Wuhan Institute of Virology Chinese Academy of SciencesWuhanChina Vaccine and Immunology Research center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghaiChina University of Chinese Academy of Sciences BeijingChina school of public health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhenGuangdongChina State Key Laboratory of Virology Modern Virology Research CenterCollege of Life SciencesWuhan UniversityWuhanChina Aerosol Bio-Tech(Suzhou)Co. LTDSuzhouJiangsuChina National Medical Products Administration Key Laboratory for Quality Monitoring and Evaluation of Vaccines and Biological Products Sun Yat-sen UniversityGuanzhouChina

Developing a mucosal vaccine against SARS-CoV-2 is critical for combatting the epidemic.Here,we investigated long-term immune responses and protection against SARS-CoV-2 for the intranasal vaccination of a triple receptor-binding domain(RBD)scaffold protein(3R-NC)adjuvanted with a flagellin protein(KFD)(3R-NC+KFDi.n).In mice,the vaccination elicited RBD-specific broad-neutralizing antibody responses in both serum and mucosal sites sustained at high level over a year.This long-lasting humoral immunity was correlated with the presence of long-lived RBD-specific IgG-and IgA-producing plasma cells,alongside the Th17 and Tfh17-biased T-cell responses driven by the KFD adjuvant.Based upon these preclinical findings,an open labeled clinical trial was conducted in individuals who had been primed with the inactivated SARS-CoV-2(IAV)vaccine.With a favorable safety profile,the 3R-NC+KFDi.n boost elicited enduring broad-neutralizing IgG in plasma and IgA in salivary secretions.To meet the challenge of frequently emerged variants,we further designed an updated triple-RBD scaffold protein with mutated RBD combinations,which can induce adaptable antibody responses to neutralize the newly emerging variants,including JN.1.Our findings highlight the potential of the KFD-adjuvanted triple-RBD scaffold protein is a promising prototype for the development of a mucosal vaccine against SARS-CoV-2 infection.

关键词： vaccination vaccine sustained

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Liquid metal biomaterials: translational medicines,challenges and perspectives

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National Science Review 2024年第2期11卷 264-284页

作者： Hanchi Xu Jincheng Lu Yikuang Xi Xuelin Wang Jing Liu Department of Biomedical Engineering School of Medicine Tsinghua University Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University shanghai World Foreign Language Academy Beijing Advanced Innovation center for Biomedical Engineering School of Engineering MedicineBeihang University Beijing Key Lab of Cryo-Biomedical Engineering and Key Lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal(LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity,and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc.Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed.Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety,material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

关键词： liquid metal biomaterials translational medicine clinical device healthcare therapeutics

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical Research center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina shanghai Engineering Research center of Stem Cells translational Medicine ShanghaiChina National center for healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research center of Digital healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Single-cell omics:experimental workflow,data analyses and applications

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Science China Life Sciences 2024年

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women’s Hospital Zhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of Statistics East China Normal University Shanghai 200062 China Department of clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of Education Orthopaedic Department Tongji Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Frontier Science center for Stem Cells School of Life Sciences and Technology Tongji University translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Research Institute of Intelligent Computing Zhejiang Lab shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River Delta Zhejiang University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

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First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao Li Rong Wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling Ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang Shuang Tong Shiqing Chen Xing Li Yongqian Shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu school Nanjing medical UniversitySuzhouChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of Medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina Jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of Medical Affairs 3D Medicines Inc.ShanghaiChina shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim prognosis.This phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction adenocarcinoma.The primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and 1b.Phase 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and S-1.Dose regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days 1-14.Dose regimen 2:same as dose regimen 1,but oxaliplatin 130mg/m.Dose regimen3:same as dose regimen 2,but apatinib 250 mg daily.Thirty-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was identified.Dose 3 was set for the recommended phase 2 doses and administered in phase 1b.The confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team evaluation.Among 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse events.Camrelizumab plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

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中国胃癌肝转移患者临床诊疗特征及预后分析:全国多中心队列研究(RECORD研究)

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Science Bulletin 2024年第3期69卷 303-307页

作者：高云鹤郗洪庆商亮唐兆庆卫勃乔治唐云王鑫鑫周静汪学非黄昌明陆俊李国新余江梁延锐季加孚李子禹薛侃梁寒柯彬臧潞何子锐谢少华黄华徐泽宽田艳涛熊建平李佶阳崔秋霞李力卢婷婷宋奇嬴刘诗贺孙益红李乐平陈凛 RECORD研究协作组 Section of Gastric Surgery Senior Department of General SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China Section of Abdominal Trauma Surgery Senior Department of General SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China Institute of General Surgery The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Gastrointestinal Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China Department of General Surgery Fudan University Zhongshan HospitalShanghai 200032China Department of General Surgery Fujian Medical University Union HospitalFuzhou 350001China Department of General Surgery Nanfang Hospital Affiliated to Southern Medical UniversityGuangzhou 510515China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastric Cancer Surgery Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Population Medicine and school of public health Fujian Medical UniversityFuzhou 350122China Department of Gastric Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of General Surgery Jiangsu Province HospitalNanjing Medical UniversityNanjing 210029China Department of Pancreatic and Gastric Surgery National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100029China

Despite surgical improvements and pharmacological advances,management of late-stage gastric cancer patients,especially those with hepatic metastasis remains challenging[1–3].Although nationwide registry data from SEER(Surveillance,Epidemiology,and End Results)[4]and the Nordic database[5]in Western countries have provided epidemiological information for patients with gastric cancer liver metastasis(GCLM),little is known about the detailed clinical characteristics.

关键词：胃癌肝转移 metastasis cancer

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Primary assessment of the diversity of Omicron sublineages and the epidemiologic features of autumn/winter 2022 COVID-19 wave in Chinese mainland

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Frontiers of Medicine 2023年第4期17卷 758-767页

作者： Gang Lu Yun Ling Minghao Jiang Yun Tan Dong Wei Lu Jiang Shuting Yu Fangying Jiang Shuai Wang Yao Dai Jinzeng Wang Geng Wu Xinxin Zhang Guoyu Meng Shengyue Wang Feng Liu Xiaohong Fan Saijuan Chen shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China shanghai public health clinical center Fudan UniversityShanghai 200083China Department of Infectious Diseases Research Laboratory of Clinical VirologyNational Research Center for Translational MedicineRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of Microbial Metabolism School of Life Sciences and BiotechnologyThe Joint International Research Laboratory of Metabolic and Developmental SciencesShanghai Jiao Tong UniversityShanghai 200240China

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures,there have been widespread SARS-CoV-2 infections in Chinese mainland.Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in shanghai,identifying a large number of sublineages of the SARS-CoV-2 Omicron family.Phylogenetic analysis,coupled with contact history tracing,revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China(BA.5.2 mainly in Guangzhou and shanghai,and BF.7 mainly in Beijing)and two highly infectious sublineages recently imported from abroad(XBB and BQ.1).publicly available data from August 31 to November 29,2022 indicated an overall severe/critical case rate of 0.035%nationwide,while analysis of 5706 symptomatic patients treated at the shanghai public health center between September 1 and December 26,2022 showed that 20 cases(0.35%)without comorbidities progressed into severe/critical conditions and 153 cases(2.68%)with COVID-19-exacerbated comorbidities progressed into severe/critical conditions.These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases.Furthermore,mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year,whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023,and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival(January 21,2023).Altogether,these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population,especially in the rural areas,to ensure the country’s smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

关键词： SARS-CoV-2 COVID-19 Omicron genomic epidemiology

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Integrated analysis of gut microbiome and host immune responses in COVID-19

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Frontiers of Medicine 2022年第2期16卷 263-275页

作者： Xiaoguang Xu Wei Zhang Mingquan Guo Chenlu Xiao Ziyu Fu Shuting Yu Lu Jiang Shengyue Wang Yun Ling Feng Liu Yun Tan Saijuan Chen shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School ofMedicineShanghai 200025China schoolof Life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China shanghai public health clinical center Shanghai 201508China Department of Laboratory Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases.Here,to explore the role of the gut microbiome in the host immune responses in COVID-19,we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples.We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones.We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity,such as Enterococcus faecium,Coprococcus comes,Roseburia intestinalis,Akkermansia ntuciniphila,Bacteroides cellulosilyticus and Blautia obeum.We further analyzed the correlation between the abundance of gut microbes and host responses,and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe,including Coprococcus comes that was positively correlated with CD3^(+)/CD4^(+)/CD8^(+)lymphocyte counts.In addition,an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells(PBMCs)showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples.Moreover,a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases,including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19.Together,our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词： COVID-19 SARS-COV-2 gut microbiome immune response

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The protective nasal boosting of a triple-RBD subunit vaccine against SARS-CoV-2 following inactivated virus vaccination

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Signal Transduction and Targeted Therapy 2023年第5期8卷 2051-2053页

作者： Jingyi Yang Mei-Qin Liu Lin Liu Xian Li Mengxin Xu Haofeng Lin Min Li Huimin Yan Yao-Qing Chen Zheng-Li Shi Vaccine and Immunology Research center Translational Medical Research InstituteShanghai Public Health Clinical CenterFudan UniversityShanghai201508China Wuhan Institute of Virology Chinese Academy of SciencesWuhan430071China school of public health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversitySun Yat-sen UniversityShenzhenGuangdong518107China

Dear Editor,Though COVID-19 vaccines have been developed and clinically deployed rapidly,new variants of concern(VOCs)are still emerging frequently and escalating around the world.More breakthrough infections occurred even vaccination rates are high.For possible ending of the pandemic,curbing infection and stopping transmission are priority.

关键词： vaccination protective nasal

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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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