COVID-19 Overview of information available to support the development of medical countermeasures and interventions against COVID-19 This document is conceived as a living document, to be updated on a weekly basis. It is based on open-access publications (scientific journals and preprint databases, communications by WHO, health authorities and companies) in English language. Please note that the present version has not been submitted to any peer-review process. Any comment / addition that can help improve the contents of this review will be most welcome. For navigation through the various sections, please click on the headings of the table of contents and follow the links marked in blue in the document. Authors: Martine Denis, Valerie Vandeweerd, Diane Van der Vliet Paper version: dd. 23 MAR 2020 Transdisciplinary Insights - Living Paper | 1 Contents List of abbreviations .......................................................................................................................................................... 6 Introduction ...................................................................................................................................................................... 7 The virus ............................................................................................................................................................................ 7 Coronaviruses ............................................................................................................................................................... 7 SARS-CoV-2 is a betacoronavirus of bat origin ............................................................................................................. 8 Genome structure ......................................................................................................................................................... 9 Sequence diversity among isolates ............................................................................................................................. 10 Phylogenetics .............................................................................................................................................................. 10 Sequence homology of the S gene .............................................................................................................................. 12 Structure of S and interactions with the ACE2 receptor ............................................................................................. 12 Other SARS-CoV-2 genes ............................................................................................................................................. 14 Immune responses to SARS-CoV-2 infection .................................................................................................................. 14 First observations in COVID-19 patients ..................................................................................................................... 14 Antigens and epitopes ................................................................................................................................................ 15 Epitope predictions ................................................................................................................................................. 15 Cross-reactivity ....................................................................................................................................................... 17 Antibody response ...................................................................................................................................................... 17 Clinical disease ................................................................................................................................................................ 17 Initial observations in Wuhan ..................................................................................................................................... 17 Incubation period ........................................................................................................................................................ 17 Description of clinical disease ..................................................................................................................................... 18 Clinical disease in China .......................................................................................................................................... 18 Clinical disease outside China ................................................................................................................................. 20 Clinical imaging ........................................................................................................................................................... 21 Laboratory finding & biomarkers ................................................................................................................................ 23 Virus load ................................................................................................................................................................ 23 Cell counts ............................................................................................................................................................... 24 Biochemistry ........................................................................................................................................................... 24 Coagulation parameters.......................................................................................................................................... 25 Time from illness onset to death ................................................................................................................................ 26 Case fatality rate ......................................................................................................................................................... 26 Case fatality rate in China ....................................................................................................................................... 26 Case fatality rate outside China .............................................................................................................................. 27 Authors: Martine Denis, Valerie Vandeweerd, Diane Van der Vliet Paper version: dd. 23 MAR 2020 Transdisciplinary Insights - Living Paper | 2 Special populations ..................................................................................................................................................... 28 Older men, cancer and immunocompromised patients ......................................................................................... 28 Children ................................................................................................................................................................... 28 Pregnancy and newborns ........................................................................................................................................ 30 Case definition ............................................................................................................................................................ 32 Definition of severe disease .................................................................................................................................... 32 Pathophysiology of COVID-19 ......................................................................................................................................... 33 Viral tropism ................................................................................................................................................................ 33 Determinants of pathogenicity ................................................................................................................................... 34 S protein and interaction with ACE2 ....................................................................................................................... 34 Infection of immune cells? ...................................................................................................................................... 34 Signs of liver injury .................................................................................................................................................. 35 Other observations ................................................................................................................................................. 35 Antibody-dependent enhancement of infection? ...................................................................................................... 35 Pathological observations from biopsies and autopsies............................................................................................. 35 Acute respiratory distress syndrome .......................................................................................................................... 36 Co-infections ............................................................................................................................................................... 37 Animal models ................................................................................................................................................................ 38 Transgenic mice