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; Kèvin Knoops; Debby Schipper; Jelte van der Vaart; Charlotte D. Koopman; Jingshu Zhang; Douglas C. Wu; Petra B. van den Doel; Theo Bestebroer; Corine H. GeurtsvanKessel; Peter J. Peters; Mauro J. Muraro; Hans Clevers; Nicholas C. Wu; Bart L. Haagmans

doi:10.1101/2021.05.03.441080

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, Kèvin Knoops, Debby Schipper, Jelte van der Vaart, Charlotte D. Koopman, Jingshu Zhang, Douglas C. Wu, Petra B. van den Doel, Theo Bestebroer, Corine H. GeurtsvanKessel, Peter J. Peters, Mauro J. Muraro, Hans Clevers, Nicholas C. Wu, Bart L. Haagmans

Research output: Working paper

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 Summary British SARS-CoV-2 variant (clade B.1.1.7) infects organoids for extended time and has a higher fitness in vitro.Competing Interest StatementH.C. is inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology. His full disclosure is given at https://www.uu.nl/staff/JCClevers/.

Original language	English (US)
Publisher	Cold Spring Harbor Laboratory Press
Number of pages	48
DOIs	https://doi.org/10.1101/2021.05.03.441080
State	In preparation - May 3 2021

Publication series

Name	bioRxiv
Publisher	Cold Spring Harbor Laboratory Press

Keywords

COVID-19
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Pandemic
Novel coronavirus
2019-nCoV
Coronavirus

Online availability

10.1101/2021.05.03.441080License: CC BY-NC-ND

Cite this

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. H., Peters, P. J., Muraro, M. J., Clevers, H., Wu, N. C., & Haagmans, B. L. (2021). Human organoid systems reveal in vitro correlates of fitness for SARS-CoV-2 B.1.1.7. (bioRxiv). Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/2021.05.03.441080

Lamers, MM, Breugem, TI, Mykytyn, AZ, Wang, Y, Groen, N, Knoops, K, Schipper, D, van der Vaart, J, Koopman, CD, Zhang, J, Wu, DC, van den Doel, PB, Bestebroer, T, GeurtsvanKessel, CH, Peters, PJ, Muraro, MJ, Clevers, H, Wu, NC & Haagmans, BL 2021 'Human organoid systems reveal in vitro correlates of fitness for SARS-CoV-2 B.1.1.7' bioRxiv, Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/2021.05.03.441080

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

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 Summary British SARS-CoV-2 variant (clade B.1.1.7) infects organoids for extended time and has a higher fitness in vitro.Competing Interest StatementH.C. is inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology. His full disclosure is given at https://www.uu.nl/staff/JCClevers/.",

keywords = "COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pandemic, Novel coronavirus, 2019-nCoV, Coronavirus",

author = "Lamers, {Mart M.} and Breugem, {Tim I.} and Mykytyn, {Anna Z.} and Yiquan Wang and Nathalie Groen and K{\`e}vin Knoops and Debby Schipper and {van der Vaart}, Jelte and Koopman, {Charlotte D.} and Jingshu Zhang and Wu, {Douglas C.} and {van den Doel}, {Petra B.} and Theo Bestebroer and GeurtsvanKessel, {Corine H.} and Peters, {Peter J.} and Muraro, {Mauro J.} and Hans Clevers and Wu, {Nicholas C.} and Haagmans, {Bart L.}",

year = "2021",

month = may,

day = "3",

doi = "10.1101/2021.05.03.441080",

language = "English (US)",

series = "bioRxiv",

publisher = "Cold Spring Harbor Laboratory Press",

address = "United States",

type = "WorkingPaper",

institution = "Cold Spring Harbor Laboratory Press",

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AU - Lamers, Mart M.

AU - Breugem, Tim I.

AU - Mykytyn, Anna Z.

AU - Wang, Yiquan

AU - Groen, Nathalie

AU - Knoops, Kèvin

AU - Schipper, Debby

AU - van der Vaart, Jelte

AU - Koopman, Charlotte D.

AU - Zhang, Jingshu

AU - Wu, Douglas C.

AU - van den Doel, Petra B.

AU - Bestebroer, Theo

AU - GeurtsvanKessel, Corine H.

AU - Peters, Peter J.

AU - Muraro, Mauro J.

AU - Clevers, Hans

AU - Wu, Nicholas C.

AU - Haagmans, Bart L.

PY - 2021/5/3

Y1 - 2021/5/3

N2 - 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.Competing Interest StatementH.C. is inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology. His full disclosure is given at https://www.uu.nl/staff/JCClevers/.

AB - 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.Competing Interest StatementH.C. is inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology. His full disclosure is given at https://www.uu.nl/staff/JCClevers/.

KW - COVID-19

KW - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

KW - Pandemic

KW - Novel coronavirus

KW - 2019-nCoV

KW - Coronavirus

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DO - 10.1101/2021.05.03.441080

M3 - Working paper

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

PB - Cold Spring Harbor Laboratory Press

ER -

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

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