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

Lamers, M. M.; Breugem, T. I.; Mykytyn, A. Z.; Wang, Y.; Groen, N.; Knoops, K.; Schipper, D.; van der Vaart, J.; Koopman, C. D.; Zhang, J.; Wu, D. C.; van den Doel, P. B.; Bestebroer, T.; GeurtsvanKessel, C. C.; Peters, P. J.; Muraro, M. J.; Clevers, H.; Wu, N. C.; Haagmans, B. L.

doi:10.1101/2021.05.03.441080

bioRxiv · 10.1101/2021.05.03.441080

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

Lamers, M. M.·Breugem, T. I.·Mykytyn, A. Z.·Wang, Y.·Groen, N.·Knoops, K.·Schipper, D.·van der Vaart, J.·Koopman, C. D.·Zhang, J.·Wu, D. C.·van den Doel, P. B.·Bestebroer, T.·GeurtsvanKessel, C. C.·Peters, P. J.·Muraro, M. J.·Clevers, H.·Wu, N. C.·Haagmans, B. L.

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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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Lamers, M. M., Breugem, T. I., Mykytyn, A. Z., Wang, Y., Groen, N., Knoops, K., Schipper, D., van der Vaart, J., Koopman, C. D., Zhang, J., Wu, D. C., van den Doel, P. B., Bestebroer, T., GeurtsvanKessel, C. C., Peters, P. J., Muraro, M. J., Clevers, H., Wu, N. C., Haagmans, B. L.. 2021-05-03. Human organoid systems reveal in vitro correlates of fitness for SARS-CoV-2 B.1.1.7. https://doi.org/10.1101/2021.05.03.441080

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