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      Host-viral infection maps reveal signatures of severe COVID-19 patients

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          Abstract

          Viruses are a constant threat to global health as highlighted by the current COVID-19 pandemic. Currently, lack of data underlying how the human host interacts with viruses, including the SARS-CoV-2 virus, limits effective therapeutic intervention. We introduce Viral-Track, a computational method that globally scans unmapped scRNA-seq data for the presence of viral RNA, enabling transcriptional cell sorting of infected versus bystander cells. We demonstrate the sensitivity and specificity of Viral-Track to systematically detect viruses from multiple models of infection, including hepatitis B virus in an unsupervised manner. Applying Viral-Track to Bronchoalveloar-Lavage samples from severe and mild COVID-19 patients reveals a dramatic impact of the virus on the immune system of severe patients compared to mild cases. Viral-Track detects an unexpected co-infection of the human MetaPneumoVirus, present mainly in monocytes perturbed in type-I IFN-signaling. Viral-Track provides a robust technology for dissecting the mechanisms of viral-infection and pathology.

          Highlights

          • Viral-track: a computational framework to analyze host-viral infection maps

          • Viral-track sorts infected from bystander cells and reveals virus-induced expression

          • SARS-CoV-2 infects epithelial cells and alters immune landscape in severe patients

          • Coinfection of SARS-Cov-2 and hMPV affects monocytes and dampen interferon response

          Abstract

          A computational framework that allows for the identification and characterizaton of virus-infected cells as well as bystander cell responses reveals how SARS-CoV-2 alters the immune responses of patients.

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          Author and article information

          Contributors
          Journal
          Cell
          Cell
          Cell
          Elsevier Inc.
          0092-8674
          1097-4172
          8 May 2020
          8 May 2020
          Affiliations
          [1 ]Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
          [2 ]Systems Biology Group, Department of Computational Biology and USR 3756, Institut Pasteur and CNRS, Paris 75015, France
          [3 ]Sorbonne Universite, Complexite du vivant, F-75005 Paris, France
          [4 ]Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen 518112, Guangdong Province, China
          [5 ]Shanghai Public Health Clinical Center and Institute of Biomedical Sciences, Fudan University, Shanghai 201508, China
          Author notes
          [∗∗ ]Corresponding author: (BS) benno@ 123456pasteur.fr
          [∗∗∗ ]Corresponding author: (ZZ) zhangzheng1975@ 123456aliyun.com
          [7 ]Corresponding author: (IA) ido.amit@ 123456weizmann.ac.il
          [∗]

          These authors contributed equally.

          [#]

          Lead contact

          Article
          S0092-8674(20)30568-7
          10.1016/j.cell.2020.05.006
          7205692
          32479746
          edf9038c-c290-4b09-87cf-c45e1017afe4
          © 2020 Elsevier Inc.

          Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

          History
          : 30 March 2020
          : 16 April 2020
          : 1 May 2020
          Categories
          Article

          Cell biology
          Cell biology

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