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Function investigation of p11.5 in ASFV infection

Virologica Sinica 2024年第3期39卷 469-477页

作者： Dan Yin Bin Shi Renhao Geng Yingnan Liu Lang Gong Hongxia Shao Kun Qian Hongjun Chen Aijian Qin Ministry of Education Key Laboratory for Avian Preventive Medicine Yangzhou UniversityJiangsu 225009China Jiangsu Co-innovation center for Prevention and Control of Important Animal infectious diseases and Zoonoses Jiangsu 225009China Joint International research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China Jiangsu 225009China Shanghai Veterinary research Institute CAASShanghai200241China South China Agricultural University Guangzhou 510642China

Virus replication relies on complex interactions between viral *** the case of African swine fever virus(ASFV),only a few such interactions have been identified so *** this study,we demonstrate that ASFV protein p72 interacts with p11.5 using co-immunoprecipitation and liquid chromatography-mass spectrometry(LC-MS).It was found that protein p72 interacts specifically with p11.5 at sites amino acids(aa)1–216 of p72 and aa 1–68 of *** assess the importance of p11.5 in ASFV infection,we developed a recombinant virus(ASFVGZΔA137R)by deleting the A137R gene from the ASFVGZ *** with ASFVGZ,the infectious progeny virus titers of ASFVGZΔA137R were reduced by approximately 1.0 *** addition,we demonstrated that the growth defect was partially attributable to a higher genome copies-to-infectious virus titer ratios produced in ASFVGZΔA137R-infected MA104 cells than in those infected with *** finding suggests that MA104 cells infected with ASFVGZΔA137R may generate larger quantities of noninfectious ***,we found that p11.5 did not affect virus-cell binding or ***,we show for the first time the interaction between ASFV p72 and *** results effectively provide the relevant information of the p11.5 *** results extend our understanding of complex interactions between viral proteins,paving the way for further studies of the potential mechanisms and pathogenesis of ASFV infection.

关键词： African swine fever virus p72 protein p11.5 protein Protein interactions

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M2-type macrophage membrane-mediated delivery of Carvedilol nanocomplex for acute liver failure treatment and remodeling inflammatory microenvironment

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Nano research 2024年第7期17卷 6362-6375页

作者： Mingge Shang Yaohui Zhang Junjie Qian Wenchao Wang Xizhi Yu Jiacheng Huang Lin Zhou Shusen Zheng Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC Key Laboratory of Combined Multi-organ Transplantation Key Laboratory of Organ TransplantationHangzhou 310003China Key Laboratory of the diagnosis and treatment of organ Transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical Sciences(2019RU019)Hangzhou 310003China State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesHangzhou 310003China Department of Thyroid Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College Hangzhou 310000China

Interactions of hepatic macrophages with local inflammatory microenvironment is the key factor promoting the development of acute liver failure(ALF).Hence,reprogramming pro-inflammatory M1 into anti-inflammatory M2 phenotype may offer a promising strategy for treating ALF by targeting *** group found Carvedilol possessed potential anti-inflammatory property previously,which had been scarcely reported in *** present a synergy strategy to induce macrophages into the phenotype M2-type anti-inflammatory macrophages with interleukin-4(IL-4)and IL-10 at *** Carvedilol is loaded on the macrophage membrane-camouflaged biomimetic nano-platform(termed as M2M@CNP)to evade reticuloendothelial system(RES)and afford Carvedilol delivery to the inflammatory environment with overproduced reactive oxygen species(ROS),further prolonging its circulation and *** released Carvedilol produced anti-inflammatory,antioxidant and anti-apoptosis effects,combining local M2-type cell membranes(M2-CM)inhibited pro-inflammatory cytokines and ROS levels,which in turn promoted and amplified M1 to M2 phenotype polarization *** study offers new insights into the rational design of biomimetic nanosystems for safe and effective ALF therapy to accelerate the clinical translation.

关键词： acute liver failure hepatic drug delivery M2 macrophage-camouflaged nanoplatform inflammatory microenvironment macrophage polarization

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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou Yuqiong Que Tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in infectious diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for infectious diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or *** rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus ***,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron ***-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric *** antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant ***,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth research center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea center for research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of infectious diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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Nonconserved epitopes dominate reverse preexisting T cell immunity in COVID-19 convalescents

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2984-2998页

作者： Xin Wang Jie Zhang Maoshun Liu Yuanyuan Guo Peipei Guo Xiaonan Yang Bingli Shang Min Li Jinmin Tian Ting Zhang Xi Wang Ronghua Jin Jikun Zhou George F.Gao Jun Liu Department of Epidemiology School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China NHC Key Laboratory of Biosafety Research Unit of Adaptive Evolution and Control of Emerging VirusesChinese Academy of Medical SciencesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China Beijing Key Laboratory of Emerging infectious diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing Institute of infectious diseases Beijing 100015China National center for infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015P.R.China School of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhou 325035China School of Ophthalmology&Optometry Wenzhou Medical UniversityWenzhou 325027China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanningGuangxi 530021China Shijiazhuang Fifth Hospital Shijiazhuang 050011China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CAS)Beijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China

The herd immunity against SARS-CoV-2 is continuously consolidated across the world during the ongoing ***,the potential function of the nonconserved epitopes in the reverse preexisting cross-reactivity induced by SARS-CoV-2 to other human coronaviruses is not well *** our research,we assessed T cell responses to both conserved and nonconserved peptides shared by SARS-CoV-2 and SARS-CoV,identifying cross-reactive CD8^(+)T cell epitopes using enzyme-linked immunospot and intracellular cytokine staining ***,in vitro refolding and circular dichroism were performed to evaluate the thermal stability of the HLA/peptide ***,single-cell T cell receptor reservoir was analyzed based on tetramer ***,we discovered that cross-reactive T cells targeting SARS-CoV were present in individuals who had recovered from COVID-19,and identified SARS-CoV-2 CD8^(+)T cell epitopes spanning the major structural antigens.T cell responses induced by the nonconserved peptides between SARS-CoV-2 and SARS-CoV were higher and played a dominant role in the cross-reactivity in COVID-19 ***-T cell reactivity was also observed within the identified series of CD8^(+)T cell *** representative immunodominant peptide pairs,although the HLA binding capacities for peptides from SARS-CoV-2 and SARS-CoV were similar,the TCR repertoires recognizing these peptides were *** results could provide beneficial information for the development of peptide-based universal vaccines against coronaviruses.

关键词： immunity conserved assessed

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Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection

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Zoological research 2024年第4期45卷 833-844页

作者： Ying Liu Lin Yang Hong-Yong Xiang Ming Niu Jia-Cheng Deng Xue-Yuan Li Wen-Jie Hao Hong-Sheng Ou-Yang Tong-Yu Liu Xiao-Chun Tang Da-Xin Pang Hong-Ming Yuan State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Animal Genome Editing Technology Innovation CenterCollege of Animal SciencesJilin UniversityChangchunJilin 130062China Chifeng Best Genetics Technology Co. Ltd.ChifengNei Mongol 024000China Chongqing Jitang Biotechnology research Institute Co. Ltd.Chongqing 400015China

Porcine reproductive and respiratory syndrome(PRRS)is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus(PRRSV),resulting in substantial economic losses in the swine *** the CD163 SRCR5 domain,either through deletion or substitution,can eff1ectively confer resistance to PRRSV infection in ***,large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth *** the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant *** the current study,we identified a specific functional amino acid in CD163 that influences PRRSV *** infection experiments conducted on Marc145 and PK-15CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV(HP-PRRSV)proliferation by preventing viral binding and ***,individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type(WT)pigs,confirming effective resistance to *** of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G *** findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs,providing novel insights into controlling future PRRSV outbreaks.

关键词： PRRSV CD163 Point mutation E529G Pigs

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Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice

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Virologica Sinica 2024年第1期39卷 97-112页

作者： Jiao Hu Zixiong Zeng Xia Chen Manyu Zhang Zenglei Hu Min Gu Xiaoquan Wang Ruyi Gao Shunlin Hu Yu Chen Xiaowen Liu Daxin Peng Xiufan Liu Animal infectious Disease Laboratory School of Veterinary MedicineYangzhou UniversityYangzhou225009China Joint International research Laboratory of Agriculture and Agri-Product Safety The Ministry of Education of ChinaYangzhou University225009China Jiangsu Co-Innovation center for Prevention and Control of Important Animal infectious diseases and Zoonosis Yangzhou UniversityYangzhou225009China Key Laboratory of Prevention and Control of Biological Hazard Factors(Animal Origin)for Agri-food Safety and Quality Ministry of Agriculture of China(26116120)Yangzhou UniversityYangzhou225009China

Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic *** modification of viral protein plays a substantial role in regulating IAV ***,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation ***,for the first time,we provide evidence that PB2 can also be acetylated at site ***,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based *** S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life *** analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein *** continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in ***,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory ***,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic ***,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.

关键词： H5N1 influenza virus PB2 Phosphorylation Acetylation Viral fitness Mice

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An MPXV mRNA-LNP vaccine candidate elicits protective immune responses against monkeypox virus

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Chinese Chemical Letters 2024年第8期35卷 466-470页

作者： Yuxin Tian Mengjun Li Yang Yang Chunhui Li Yun Peng Haiyin Yang Mengyuan Zhao Pengfei Wu Shaobo Ruan Yuanyu Huang Chenguang Shen Minghui Yang Advanced research Institute of Multidisciplinary Science School of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyBeijing Institute of TechnologyBeijing 100081China BSL-3 Laboratory(Guangdong) Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthDepartment of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510280China National Clinical research center for infectious disease Shenzhen Third People’s HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China

The monkeypox virus(MPXV)outbreak,declared a Public Health Emergency of International Concern(PHEIC)by the World Health Organization(WHO)in 2022,continues to pose a significant threat due to the absence of vaccines or drugs for MPXV *** this study,we developed an mRNA vaccine that expressing the A29L antigen,a specific protein of the intracellular mature *** vaccine utilizes a thermostable ionizable lipid nanoparticle(iLNP)platform and has been administered to *** find-ings demonstrate that the MPXV A29L mRNA vaccine candidate induces robust cross-neutralizing immune responses against both vaccinia virus(VACV)and MPXV live ***,immunization with the vaccine candidate provided protection against the VACV challenge in *** findings underscore the potential of mRNA-LNP vaccines as safe and effective candidates against monkeypox *** the current absence of specific interventions for MPXV infection,our study represents a significant step forward in developing a viable solution to combat this ongoing public health threat.

关键词： Monkeypox virus mRNA vaccine Lipid-nano particle A29L VACV

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Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers:A case report and review of literature

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 932-943页

作者： Yong-Jing Tang Jian Zhang Jie Wang Ren-Dong Tian Wei-Wei Zhong Ben-Sheng Yao Bing-Yu Hou Ying-Hua Chen Wei He Yi-Huai He Department of infectious diseases The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Gastroenterology Dafang County People's HospitalBijie 551600Guizhou ProvinceChina Department of Internal Medicine Puchang BranchMedical CommunitySuiyang County People's HospitalZunyi 563300Guizhou ProvinceChina Department of infectious diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina Department of infectious diseases Dafang County People's HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering *** present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant *** SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark *** the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic *** surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess *** patient’s condition improved and he was ***,the recurrent episodes of abdominal pain and passage of black stools started again one year after *** the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve *** investigations revealed mutations in the ACVRL1 and PLA2G4A ***1 and PLA2G4A are involved in angiogenesis and coagulation,*** suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A *** Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical *** Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in *** administered Kangfuxin liquid may have therapeutic potential.

关键词： Intestinal ulcers Crohn’s disease Ulcerative colitis Activin A receptor type II-like 1 Phospholipase A2 group 4A Case report

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COVID-19/Tuberculosis Co-Infection at the Epidemic Treatment center (ETC) of Saint-Louis (Senegal): About 9 Cases

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Advances in infectious diseases 2024年第1期14卷 56-66页

作者： Alassane Dièye Moustapha Diedhiou Papa Latyr Junior Diouf Mba Bambo Diakhaby Demba Makalou Samba Niang Diatou Dia-Gueye Amadou Diop Dia Ibrahima Louis Martin Dieng Seynabou Lô Ndéye Méry Dia-Badiane Health Sciences Training and research Unit Gaston Berger University Saint-Louis Senegal Department of Medicine Saint-Louis Regional Hospital Saint-Louis Senegal infectious and tropical diseases Clinic of Fann Dakar Senegal

Introduction: COVID-19 is a global public health emergency that can cause acute respiratory distress syndrome. In countries where tuberculosis (TB) is endemic, coinfection of COVID-19 and TB is often encountered, which increases the risk of developing severe forms of COVID-19. Objectives: The aim of this study was to determine the prevalence of COVID-19/TB coinfection at the Epidemic treatment center (ETC) in Saint-Louis (Senegal) and to describe the epidemiological, clinical, paraclinical, and outcome profile of co-infected patients. Patients and Methods: This is a retrospective, cross-sectional, descriptive cohort study based on the records of COVID-19/ TB co-infected patients who were hospitalized at the ETC in Saint-Louis (Senegal) over an 18-month period from March 2020 to September 2021. Results: Out of a total of 454 hospitalizations, we collected records of 9 patients co-infected with COVID-19/TB, resulting in a prevalence of 2%. The study included patients with a median age of 34 years (range: 10-86 years), with a male predominance (7 cases) and a sex ratio of 3.5. The majority of patients (88.9%) had severe forms of COVID-19. Dyspnea and cough were reported in all patients (100%). Pulmonary TB was the most frequent localization, with 9 cases. The diagnosis of COVID-19 was confirmed by nasopharyngeal PCR in all patients (100%). Bacilloscopy was positive in 3 out of 5 cases. One patient tested positive for GeneXpert? MTB/RIF without rifampicin resistance. All patients were prescribed the hydroxychloroquine-azithromycin combination and anti-tuberculosis treatment. Out of the nine patients, four recovered (44.4%) and five died (55.5%). Conclusion: COVID-19/TB coinfection had a low prevalence in our cohort, but was associated with a high mortality due to the frequent occurrence of severe forms of the disease.

关键词： COVID-19 Tuberculosis Saint-Louis Senegal

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