2021-07-06

Department of Epidemiology, Fielding School of Public Health, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY 14214, USA.; Department of Environmental Health Science, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Institute of the Environment and Sustainability, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Department of Epidemiology, Fielding School of Public Health, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; WORLD Policy Analysis Center, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Department of Epidemiology, Fielding School of Public Health, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.; Center for Human Nutrition, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.

Long-term PM(2.5) exposure might predispose populations to SARS-CoV-2 infection and intervention policies might interrupt SARS-CoV-2 transmission and reduce the risk of COVID-19. We conducted an ecologic study across the United States, using county-level COVID-19 incidence up to 12 September 2020, to represent the first two surges in the U.S., annual average of PM(2.5) between 2000 and 2016 and state-level facemask mandates and stay home orders. We fit negative binomial models to assess COVID-19 incidence in association with PM(2.5) and policies. Stratified analyses by facemask policy and stay home policy were also performed. Each 1-µg/m(3) increase in annual average concentration of PM(2.5) exposure was associated with 7.56% (95% CI: 3.76%, 11.49%) increase in COVID-19 risk. Facemask mandates and stay home policies were inversely associated with COVID-19 with adjusted RRs of 0.8466 (95% CI: 0.7598, 0.9432) and 0.9193 (95% CI: 0.8021, 1.0537), respectively. The associations between PM

2021-04-29

Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Emergency, Dongfeng Maojian Hospital, Sinopharm Group Corporation, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Infectious Diseases, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Department of Respiratory, Renmin Hospital, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, China.; Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan, China.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), which is causing the coronavirus disease-2019 (COVID-19) pandemic, poses a global health threat. However, it is easy to confuse COVID-19 with seasonal influenza in preliminary clinical diagnosis. In this study, the differences between influenza and COVID-19 in epidemiological features, clinical manifestations, comorbidities and pathogen biology were comprehensively compared and analyzed. SARS-CoV-2 causes a higher proportion of pneumonia (90.67 vs. 17.07%) and acute respiratory distress syndrome (12.00 vs. 0%) than influenza A virus. The proportion of leukopenia for influenza patients was 31.71% compared with 12.00% for COVID-19 patients (P = 0.0096). The creatinine and creatine kinase were significantly elevated when there were COVID-19 patients. The basic reproductive number (R(0)) for SARS-CoV-2 is 2.38 compared with 1.28 for seasonal influenza A virus. The mutation rate of SARS-CoV-2 ranges from 1.12 ×

2021-04-11

MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China.; NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China.; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China.; Wellcome Trust/Cancer Research UK Gurdon Institute, Department of Genetics, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, CB10 1SA, UK.; Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: qding@tsinghua.edu.cn.; NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. Electronic address: wangjw28@163.com.; MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; Tsinghua-Peking Center for Life Sciences, Beijing 100084, China. Electronic address: qczhang@tsinghua.edu.cn.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding of the RNA virus and its interactions with host proteins could improve therapeutic interventions for COVID-19. By using icSHAPE, we determined the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as the regulatory untranslated regions of SARS-CoV-2 and six other coronaviruses. We validated several structural elements predicted in silico and discovered structural features that affect the translation and abundance of subgenomic viral RNAs in cells. The structural data informed a deep-learning tool to predict 42 host proteins that bind to SARS-CoV-2 RNA. Strikingly, antisense oligonucleotides targeting the structural elements and FDA-approved drugs inhibiting the SARS-CoV-2 RNA binding proteins dramatically reduced SARS-CoV-2 infection in cells derived from human liver and lung tumors. Our

2021-11-14

Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. zhouzhuo@gmail.com.; Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China.; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.; Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Pseking University, Beijing, 100871, China.; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.; Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, Peking-Tsinghua Center for Life Sciences, Peking University Genome Editing Research Center, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China. wswei@pku.edu.cn.; NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China. wangjw28@163.com.; Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China. wangjw28@163.com.; Christophe Merieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, P.R. China. wangjw28@163.com.

The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for