Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study
Barnaby E Young,
Wycliffe E Wei,
Siew-Wai Fong,
Tze-Minn Mak,
Danielle E Anderson,
Yi-Hao Chan,
Rachael Pung,
Cheryl SY Heng,
Li Wei Ang,
Adrian Kang Eng Zheng,
Bernett Lee,
Shirin Kalimuddin,
Surinder Pada,
Paul A Tambyah,
Purnima Parthasarathy,
Seow Yen Tan,
Louisa Sun,
Gavin JD Smith,
Raymond Tzer Pin Lin,
Yee-Sin Leo,
Laurent Renia,
Lin-Fa Wang,
Lisa FP Ng,
Sebastian Maurer-Stroh,
David Chien Lye,
Vernon J Lee
Affiliations
Barnaby E Young
National Centre for Infectious Diseases, Singapore; Deaprtment of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
Wycliffe E Wei
National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore; Singapore Ministry of Health, Singapore
Siew-Wai Fong
A*STAR ID Labs, Agency for Science, Technology and Research (A*STAR), Singapore; Singapore Immunology Network, A*STAR, Singapore; Department of Biological Science, National University of Singapore, Singapore
Tze-Minn Mak
National Centre for Infectious Diseases, Singapore
Singapore Ministry of Health, Singapore; London School of Hygiene and Tropical Medicine, London, UK
Cheryl SY Heng
Singapore Ministry of Health, Singapore
Li Wei Ang
National Public Health and Epidemiology Unit, National Centre for Infectious Diseases, Singapore
Adrian Kang Eng Zheng
Duke NUS Medical School, Singapore
Bernett Lee
Singapore Immunology Network, A*STAR, Singapore
Shirin Kalimuddin
Duke NUS Medical School, Singapore; Singapore General Hospital of Singapore, Singapore
Surinder Pada
Ng Teng Fong General Hospital, Singapore
Paul A Tambyah
Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Purnima Parthasarathy
Khoo Teck Puat Hospital, Singapore
Seow Yen Tan
Changi General Hospital, Singapore
Louisa Sun
Alexandra Hospital, Singapore
Gavin JD Smith
Duke NUS Medical School, Singapore
Raymond Tzer Pin Lin
National Centre for Infectious Diseases, Singapore
Yee-Sin Leo
National Centre for Infectious Diseases, Singapore; Deaprtment of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore
Bioinformatics Institute, Agency for Science, Technology and Research, Singapore; Corresponding authors.
David Chien Lye
National Centre for Infectious Diseases, Singapore; Deaprtment of Infectious Diseases, Tan Tock Seng Hospital, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Vernon J Lee
Singapore Ministry of Health, Singapore; Saw Swee Hock School of Public Health, National University of Singapore, Singapore; Corresponding authors.
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.
