2021-05-09

Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.; Therapeutic Innovation Center, Baylor College of Medicine, Houston, TX 77030, USA.; Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA.; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Single-cell RNA sequencing of the bronchoalveolar lavage fluid (BALF) samples from COVID-19 patients has enabled us to examine gene expression changes of human tissue in response to the SARS-CoV-2 virus infection. However, the underlying mechanisms of COVID-19 pathogenesis at single-cell resolution, its transcriptional drivers, and dynamics require further investigation. In this study, we applied machine learning algorithms to infer the trajectories of cellular changes and identify their transcriptional programs. Our study generated cellular trajectories that show the COVID-19 pathogenesis of healthy-to-moderate and healthy-to-severe on macrophages and T cells, and we observed more diverse trajectories in macrophages compared to T cells. Furthermore, our deep-learning algorithm DrivAER identified several pathways (e.g., xenobiotic pathway and complement pathway) and transcription factors (e.g., MITF and GATA3) that could be potential drivers of the transcriptomic changes for COVID-19

2021-02-21

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, The Fourth Affiliated Hospital of Nantong University, The First People's Hospital of Yancheng, Yancheng, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The catastrophic outbreak of coronavirus disease 2019 (COVID-19) is currently a public emergency. Adult-onset Still's disease (AOSD) is an autoinflammatory disease characterized by life-threatening complications. Systemic hyperinflammation and cytokine storm play a critical role in the pathogenesis of both COVID-19 and AOSD. We aimed to compare the similarities and differences focusing on ferritin and cytokine levels between severe COVID-19 and active AOSD. A literature search was performed using the databases PubMed, EMBASE, and Web of Science to collect the levels of cytokine including IL-1β, IL-6, IL-18, TNF-α, IL-10, and ferritin in severe COVID-19 patients. After extracting available data of indicators of interest, we acquired these statistics with a single-arm meta-analysis. Furthermore, a comparison was conducted between 52 patients with active AOSD in our center and severe COVID-19 patients from databases. The levels of IL-6 and IL-10 were higher in severe COVID-19 compared

2021-09-22

Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, North Huashan Hospital, Fudan University, Shanghai, China.; Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University, School of medicine, Shanghai, China.; Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Institute of Respiratory Diseases, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Houston Kidney Consultants, Houston, TX, USA.; Houston Methodist Institute for Academic Medicine, Houston, TX, USA.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Wuhan Ninth Hospital, Wuhan, China.; Renal Department, Wuhan Ninth Hospital, Wuhan, Hubei, China.; Radiology Department of Renmin Hospital, Wuhan University, Wuhan, Hubei, China.; Renal Department of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.; Renal Department of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.; Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Endocrinology and Metabolism disease, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.; Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.; Division of Nephrology, Mount Sinai School of Medicine, New York, NY, USA.; Renal Department of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin

2021-07-25

Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, North Huashan Hospital, Fudan University, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Wuhan Ninth Hospital, Wuhan, PR China.; Renal Department, Wuhan Ninth Hospital, Wuhan, PR China.; Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, PR China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, PR China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, PR China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, PR China.; Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University, School of medicine, Shanghai, PR China.; Department of Endocrinology and Metabolism disease, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.; Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.; Renal Department of Renmin Hospital, Renmin Hospital of Wuhan University, Wuhan, PR China.; Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, PR China.; Department of Nephrology, Institute of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.

INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. METHODS: Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. RESULTS: Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84-0.91). Next, we determined

2021-05-30

National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. hjbian@fmmu.edu.cn.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; College of Military Preventive Medicine, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; Department of Pharmaceutics, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Department of Pathology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; Center for Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.; College of Military Preventive Medicine, Fourth Military Medical University, Xi'an, China.; Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.; Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.; Jiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd, Changzhou, China.; Department of Foreign Languages, Fourth Military Medical University, Xi'an, China.; National Translational Science Center for Molecular Medicine and Department of Cell Biology, Fourth Military Medical University, Xi'an, China. znchen@fmmu.edu.cn.; Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. zhuping@fmmu.edu.cn.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG(2) monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood C(max) and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between