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Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19

View ORCID ProfileGuillaume Carissimo, Weili Xu, Immanuel Kwok, Mohammad Yazid Abdad, Yi-Hao Chan, Siew-Wai Fong, Kia Joo Puan, Cheryl Yi-Pin Lee, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Wilson How, Stephrene Chan, Eugene Bingwen Fan, Anand Kumar Andiappan, Bernett Lee, Olaf Rötzschke, Barnaby Edward Young, Yee-Sin Leo, David C. Lye, Laurent Renia, Lai Guan Ng, Anis Larbi, Lisa F.P. Ng
doi: https://doi.org/10.1101/2020.06.11.147389
Guillaume Carissimo
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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  • ORCID record for Guillaume Carissimo
Weili Xu
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Immanuel Kwok
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Mohammad Yazid Abdad
2National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore
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Yi-Hao Chan
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Siew-Wai Fong
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
3Department of Biological Sciences, National University of Singapore, Singapore 117543
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Kia Joo Puan
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Cheryl Yi-Pin Lee
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Nicholas Kim-Wah Yeo
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Siti Naqiah Amrun
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Rhonda Sin-Ling Chee
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Wilson How
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Stephrene Chan
4Department of Haematology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore
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Eugene Bingwen Fan
4Department of Haematology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore
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Anand Kumar Andiappan
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Bernett Lee
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Olaf Rötzschke
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Barnaby Edward Young
2National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore
5Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore
6Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore
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Yee-Sin Leo
2National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore
5Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore
6Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore
7Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 10 Medical Drive, 117597, Singapore
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David C. Lye
2National Centre for Infectious Diseases, 16 Jalan Tan Tock Seng, 308442, Singapore
5Department of Infectious Diseases, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore
6Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, 308232, Singapore
7Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 10 Medical Drive, 117597, Singapore
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Laurent Renia
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Lai Guan Ng
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Anis Larbi
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
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Lisa F.P. Ng
1Singapore Immunology Network, Agency for Science, Technology and Research, Immunos, Biopolis, 138648, Singapore
8Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117596, Singapore
9Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, 8 West Derby Street, Liverpool L7 3EA, United Kingdom
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  • For correspondence: lisa_ng@immunol.a-star.edu.sg
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Abstract

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 γδ T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 12, 2020.
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Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19
Guillaume Carissimo, Weili Xu, Immanuel Kwok, Mohammad Yazid Abdad, Yi-Hao Chan, Siew-Wai Fong, Kia Joo Puan, Cheryl Yi-Pin Lee, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Wilson How, Stephrene Chan, Eugene Bingwen Fan, Anand Kumar Andiappan, Bernett Lee, Olaf Rötzschke, Barnaby Edward Young, Yee-Sin Leo, David C. Lye, Laurent Renia, Lai Guan Ng, Anis Larbi, Lisa F.P. Ng
bioRxiv 2020.06.11.147389; doi: https://doi.org/10.1101/2020.06.11.147389
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Whole blood immunophenotyping uncovers immature neutrophil-to-VD2 T-cell ratio as an early prognostic marker for severe COVID-19
Guillaume Carissimo, Weili Xu, Immanuel Kwok, Mohammad Yazid Abdad, Yi-Hao Chan, Siew-Wai Fong, Kia Joo Puan, Cheryl Yi-Pin Lee, Nicholas Kim-Wah Yeo, Siti Naqiah Amrun, Rhonda Sin-Ling Chee, Wilson How, Stephrene Chan, Eugene Bingwen Fan, Anand Kumar Andiappan, Bernett Lee, Olaf Rötzschke, Barnaby Edward Young, Yee-Sin Leo, David C. Lye, Laurent Renia, Lai Guan Ng, Anis Larbi, Lisa F.P. Ng
bioRxiv 2020.06.11.147389; doi: https://doi.org/10.1101/2020.06.11.147389

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