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Title: Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: an observational study
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.
Keywords: Science::Medicine
Issue Date: 2021
Source: 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-.
Journal: EBioMedicine
Abstract: 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.
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2021.103319
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: National Centre for Infectious Diseases
Tan Tock Seng Hospital
National University of Singapore
Rights: © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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