Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study
Barnaby Edward Young, Wycliffe Enli 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 Anantharajah Tambyah, Purnima Parthasarathy, Seow Yen Tan, Louisa Sun, Gavin J. D. Smith, Raymond Tzer Pin Lin, Yee‐Sin Leo, Laurent Rénia, Lin‐Fa Wang, Lisa F. P. Ng, Sebastian Maurer‐Stroh, David Chien Lye, Vernon J. Lee
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.