Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study

Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational coho...

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Main Authors: Young, Barnaby Edward, Wei, Wycliffe E., Fong, Siew-Wai, Mak, Tze-Minn, Anderson, Danielle E., Chan, Yi-Hao, Pung, Rachael, Heng, Cheryl S. Y., Ang, Li Wei, Zheng, Adrian Kang Eng, Lee, Bernett, Kalimuddin, Shirin, Pada, Surinder, Tambyah, Paul A., Parthasarathy, Purnima, Tan, Seow Yen, Sun, Louisa, Smith, Gavin J. D., Lin, Raymond Tzer Pin, Leo, Yee Sin, Renia, Laurent, Wang, Lin-Fa, Ng, Lisa F. P., Maurer-Stroh, Sebastian, Lye, David C., Lee, Vernon J.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/154214
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1542142023-03-05T16:51:39Z Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study Young, Barnaby Edward Wei, Wycliffe E. Fong, Siew-Wai Mak, Tze-Minn Anderson, Danielle E. Chan, Yi-Hao Pung, Rachael Heng, Cheryl S. Y. Ang, Li Wei Zheng, Adrian Kang Eng Lee, Bernett Kalimuddin, Shirin Pada, Surinder Tambyah, Paul A. Parthasarathy, Purnima Tan, Seow Yen Sun, Louisa Smith, Gavin J. D. Lin, Raymond Tzer Pin Leo, Yee Sin Renia, Laurent Wang, Lin-Fa Ng, Lisa F. P. Maurer-Stroh, Sebastian Lye, David C. Lee, Vernon J. Lee Kong Chian School of Medicine (LKCMedicine) National Centre for Infectious Diseases Tan Tock Seng Hospital National University of Singapore Science::Medicine Clade Severity Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. Findings: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades ‘O’ were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002–0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064–0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35–2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. Interpretation: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility. Published version 2022-05-24T08:39:47Z 2022-05-24T08:39:47Z 2021 Journal Article Young, B. E., Wei, W. E., Fong, S., Mak, T., Anderson, D. E., Chan, Y., Pung, R., Heng, C. S. Y., Ang, L. W., Zheng, A. K. E., Lee, B., Kalimuddin, S., Pada, S., Tambyah, P. A., Parthasarathy, P., Tan, S. Y., Sun, L., Smith, G. J. D., Lin, R. T. P., ...Lee, V. J. (2021). Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study. EBioMedicine, 66, 103319-. https://dx.doi.org/10.1016/j.ebiom.2021.103319 2352-3964 https://hdl.handle.net/10356/154214 10.1016/j.ebiom.2021.103319 33840632 2-s2.0-85103987600 66 103319 en EBioMedicine © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Clade
Severity
spellingShingle Science::Medicine
Clade
Severity
Young, Barnaby Edward
Wei, Wycliffe E.
Fong, Siew-Wai
Mak, Tze-Minn
Anderson, Danielle E.
Chan, Yi-Hao
Pung, Rachael
Heng, Cheryl S. Y.
Ang, Li Wei
Zheng, Adrian Kang Eng
Lee, Bernett
Kalimuddin, Shirin
Pada, Surinder
Tambyah, Paul A.
Parthasarathy, Purnima
Tan, Seow Yen
Sun, Louisa
Smith, Gavin J. D.
Lin, Raymond Tzer Pin
Leo, Yee Sin
Renia, Laurent
Wang, Lin-Fa
Ng, Lisa F. P.
Maurer-Stroh, Sebastian
Lye, David C.
Lee, Vernon J.
Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
description Background: Host determinants of severe coronavirus disease 2019 include advanced age, comorbidities and male sex. Virologic factors may also be important in determining clinical outcome and transmission rates, but limited patient-level data is available. Methods: We conducted an observational cohort study at seven public hospitals in Singapore. Clinical and laboratory data were collected and compared between individuals infected with different SARS-CoV-2 clades. Firth's logistic regression was used to examine the association between SARS-CoV-2 clade and development of hypoxia, and quasi-Poisson regression to compare transmission rates. Plasma samples were tested for immune mediator levels and the kinetics of viral replication in cell culture were compared. Findings: 319 patients with PCR-confirmed SARS-CoV-2 infection had clinical and virologic data available for analysis. 29 (9%) were infected with clade S, 90 (28%) with clade L/V, 96 (30%) with clade G (containing D614G variant), and 104 (33%) with other clades ‘O’ were assigned to lineage B.6. After adjusting for age and other covariates, infections with clade S (adjusted odds ratio (aOR) 0·030 (95% confidence intervals (CI): 0·0002–0·29)) or clade O (B·6) (aOR 0·26 (95% CI 0·064–0·93)) were associated with lower odds of developing hypoxia requiring supplemental oxygen compared with clade L/V. Patients infected with clade L/V had more pronounced systemic inflammation with higher concentrations of pro-inflammatory cytokines, chemokines and growth factors. No significant difference in the severity of clade G infections was observed (aOR 0·95 (95% CI: 0·35–2·52). Though viral loads were significantly higher, there was no evidence of increased transmissibility of clade G, and replicative fitness in cell culture was similar for all clades. Interpretation: Infection with clades L/V was associated with increased severity and more systemic release of pro-inflammatory cytokines. Infection with clade G was not associated with changes in severity, and despite higher viral loads there was no evidence of increased transmissibility.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Young, Barnaby Edward
Wei, Wycliffe E.
Fong, Siew-Wai
Mak, Tze-Minn
Anderson, Danielle E.
Chan, Yi-Hao
Pung, Rachael
Heng, Cheryl S. Y.
Ang, Li Wei
Zheng, Adrian Kang Eng
Lee, Bernett
Kalimuddin, Shirin
Pada, Surinder
Tambyah, Paul A.
Parthasarathy, Purnima
Tan, Seow Yen
Sun, Louisa
Smith, Gavin J. D.
Lin, Raymond Tzer Pin
Leo, Yee Sin
Renia, Laurent
Wang, Lin-Fa
Ng, Lisa F. P.
Maurer-Stroh, Sebastian
Lye, David C.
Lee, Vernon J.
format Article
author Young, Barnaby Edward
Wei, Wycliffe E.
Fong, Siew-Wai
Mak, Tze-Minn
Anderson, Danielle E.
Chan, Yi-Hao
Pung, Rachael
Heng, Cheryl S. Y.
Ang, Li Wei
Zheng, Adrian Kang Eng
Lee, Bernett
Kalimuddin, Shirin
Pada, Surinder
Tambyah, Paul A.
Parthasarathy, Purnima
Tan, Seow Yen
Sun, Louisa
Smith, Gavin J. D.
Lin, Raymond Tzer Pin
Leo, Yee Sin
Renia, Laurent
Wang, Lin-Fa
Ng, Lisa F. P.
Maurer-Stroh, Sebastian
Lye, David C.
Lee, Vernon J.
author_sort Young, Barnaby Edward
title Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
title_short Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
title_full Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
title_fullStr Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
title_full_unstemmed Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
title_sort association of sars-cov-2 clades with clinical, inflammatory and virologic outcomes: an observational study
publishDate 2022
url https://hdl.handle.net/10356/154214
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