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Human organoid systems reveal in vitro correlates of fitness for SARS-CoV-2 B.1.1.7
Mart M Lamers; Tim I Breugem; Anna Z Mykytyn; Yiquan Wang; Nathalie Groen; Kevin Knoops; Debby Schipper; Jelte van der Vaart; Charlotte D Koopman; Jingshu Zhang; Douglas C Wu; Petra B van den Doel; Theo Bestebroer; Corine C GeurtsvanKessel; Peter J Peters; Mauro J Muraro; Hans Clevers; Nicholas C Wu; Bart L Haagmans.
Affiliation
  • Mart M Lamers; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Tim I Breugem; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Anna Z Mykytyn; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Yiquan Wang; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
  • Nathalie Groen; Single Cell Discoveries, Utrecht, The Netherlands.
  • Kevin Knoops; The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, Netherlands.
  • Debby Schipper; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Jelte van der Vaart; Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands.
  • Charlotte D Koopman; Single Cell Discoveries, Utrecht, The Netherlands.
  • Jingshu Zhang; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Douglas C Wu; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
  • Petra B van den Doel; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Theo Bestebroer; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Corine C GeurtsvanKessel; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
  • Peter J Peters; The Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, Netherlands.
  • Mauro J Muraro; Single Cell Discoveries, Utrecht, The Netherlands.
  • Hans Clevers; Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands.
  • Nicholas C Wu; Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
  • Bart L Haagmans; Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.
Preprint in English | bioRxiv | ID: ppbiorxiv-441080
ABSTRACT
A new phase of the COVID-19 pandemic has started as several SARS-CoV-2 variants are rapidly emerging globally, raising concerns for increased transmissibility. As animal models and traditional in vitro systems may fail to model key aspects of the SARS-CoV-2 replication cycle, representative in vitro systems to assess variants phenotypically are urgently needed. We found that the British variant (clade B.1.1.7), compared to an ancestral SARS-CoV-2 clade B virus, produced higher levels of infectious virus late in infection and had a higher replicative fitness in human airway, alveolar and intestinal organoid models. Our findings unveil human organoids as powerful tools to phenotype viral variants and suggest extended shedding as a correlate of fitness for SARS-CoV-2. One-Sentence SummaryBritish SARS-CoV-2 variant (clade B.1.1.7) infects organoids for extended time and has a higher fitness in vitro.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2021 Document type: Preprint
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