Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Abstract A global pandemic of the 2019 coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is responsible for over 150,000 deaths worldwide, including >12,000 deaths in New York City (NYC) alone. There is a pressing clinical and public health need for scalable molecular technologies that can rapidly detect SARS-CoV-2 infection and robustly interrogate strain evolution and host response in patients. To address these challenges, we designed a loop-mediated isothermal amplification (LAMP) assay to identify SARS-CoV-2 infection within 30 minutes of application, including directly from lysed cells. Simultaneously, we developed a large-scale host and viral transcriptomic profiling platform that employs total RNA sequencing of nasopharyngeal swab specimens. Applying both technologies to 442 samples, spanning 338 clinical samples tested for SARS-CoV-2, 86 environmental samples from the NYC subway, and 14 controls, we assembled a broad molecular picture of the COVID-19 epidemic in NYC. We found close concordance between viral titers measured with our rapid LAMP assay, RNA-seq, and the state-of-the-art RT-PCR. Full transcriptomic analyses revealed a distinct subset of the Western European clade A2a as the predominant genomic subtype in NYC cases, which was defined by two single nucleotide variants in nsp2 and ORF 3a and a clade-specific, 9-bp in-frame deletion in the virulence factor nsp1. High SARS-Cov2 viral titers were associated with distinct host transcriptional responses, including activation of the ACE2 gene and interferon response genes (e.g., IFIT1). Since ACE inhibitors (ACEIs) can also increase ACE2 expression, outcomes for patients taking ACEIs were examined, and showed a significantly increased risk of intubation and death. Our results demonstrate the utility of two molecular diagnostic platforms in defining the genetic features of an evolving global pandemic and provide insights that can aid future COVID-19 diagnostics, public health monitoring, and therapeutic options.
Mason Christopher E.、Butler Daniel J.、Mozsary Christopher、Danko David、Imielinski Marcin、Melnick Ari M.、Loda Massimo、Rosiene Joel、Shaiber Alon、MacKay Matthew、Ivanov Nikolay A.、Sierra Maria、Pohle Diana、Gisladottir Undina、Langhorst Bradley W.、Tanner Nathan、Xu Dong、Iftner Angelika、Bezdan Daniela、Velu Priya、Salvatore Mirella、Meydan Cem、Meleshko Dmitry、Iftner Thomas、Craney Arryn、Westover Craig D.、Cushing Melissa、Levy Shawn、Zietz Michael、Ryon Krista、Sipley John、Gawrys Justyna、Xiang Jenny、Afshinnekoo Ebrahim、Tatonetti Nicholas、Cong Lin、Hajirasouliha Iman、Sedlazeck Fritz J.、Westblade Lars F.、Rennert Hanna、Ruggiero Phyllis、Bhattacharya Chandrima、Young Benjamin、Foox Jonathan
Department of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||New York Genome Center||The Feil Family Brain and Mind Research Institute, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||Tri-Institutional Computational Biol. & Medicine Program, Weill Cornell MedicineNew York Genome Center||Department of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Medicine, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineNew York Genome Center||Department of Pathology and Laboratory Medicine, Weill Cornell MedicineNew York Genome Center||Department of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||Clinical & Translational Science Center, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineInstitute of Medical Virology and Epidemiology of Viral Diseases, University Hospital TuebingenDepartment of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia UniversityNew England BiolabsNew England BiolabsGenomics Resources Core Facility, Weill Cornell MedicineInstitute of Medical Virology and Epidemiology of Viral Diseases, University Hospital TuebingenInstitute of Medical Virology and Epidemiology of Viral Diseases, University Hospital TuebingenDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineDivision of Infectious Diseases, Department of Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||WorldQuant Initiative for Quantitative Prediction, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||Tri-Institutional Computational Biol. & Medicine Program, Weill Cornell MedicineInstitute of Medical Virology and Epidemiology of Viral Diseases, University Hospital TuebingenDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineHudsonAlpha Discovery InstituteDepartment of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia UniversityDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineClinical & Translational Science Center, Weill Cornell Medicine||Genomics Resources Core Facility, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||WorldQuant Initiative for Quantitative Prediction, Weill Cornell MedicineDepartment of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia UniversityDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine||Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell MedicineBaylor College of MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell Medicine||Division of Infectious Diseases, Department of Medicine, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Pathology and Laboratory Medicine, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell MedicineDepartment of Physiology and Biophysics, Weill Cornell Medicine||The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine
医学研究方法基础医学分子生物学
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)2019 coronavirus disease (COVID-19)loop-mediated isothermal amplification (LAMP)real-time polymerase chain reaction (RT-PCR)next-generation sequencing (NGS)RNA-seqglobal health
Mason Christopher E.,Butler Daniel J.,Mozsary Christopher,Danko David,Imielinski Marcin,Melnick Ari M.,Loda Massimo,Rosiene Joel,Shaiber Alon,MacKay Matthew,Ivanov Nikolay A.,Sierra Maria,Pohle Diana,Gisladottir Undina,Langhorst Bradley W.,Tanner Nathan,Xu Dong,Iftner Angelika,Bezdan Daniela,Velu Priya,Salvatore Mirella,Meydan Cem,Meleshko Dmitry,Iftner Thomas,Craney Arryn,Westover Craig D.,Cushing Melissa,Levy Shawn,Zietz Michael,Ryon Krista,Sipley John,Gawrys Justyna,Xiang Jenny,Afshinnekoo Ebrahim,Tatonetti Nicholas,Cong Lin,Hajirasouliha Iman,Sedlazeck Fritz J.,Westblade Lars F.,Rennert Hanna,Ruggiero Phyllis,Bhattacharya Chandrima,Young Benjamin,Foox Jonathan.Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2020.04.20.048066.点此复制
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