Human organoid systems reveal in vitro correlates of fitness for SARS-CoV-2 B.1.1.7

Lamers, Mart M.; Breugem, Tim I.; Mykytyn, Anna Z.; Wang, Yiquan; Groen, Nathalie; Knoops, Kèvin; Schipper, Debby; van der Vaart, Jelte; Koopman, Charlotte D.; Zhang, Jingshu; Wu, Douglas C.; van den Doel, Petra B.; Bestebroer, Theo; GeurtsvanKessel, Corine H.; Peters, Peter J.; Muraro, Mauro J.; Clevers, Hans; Wu, Nicholas C.; Haagmans, Bart L.

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 Summary British SARS-CoV-2 variant (clade B.1.1.7) infects organoids for extended time and has a higher fitness in vitro.