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

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EBioMedicine


. 2021 Apr 8;103319.
doi: 10.1016/j.ebiom.2021.103319. Online ahead of print.
Association of SARS-CoV-2 clades with clinical, inflammatory and virologic outcomes: An observational study


Barnaby E Young ¹ , Wycliffe E Wei ² , Siew-Wai Fong ³ , Tze-Minn Mak ⁴ , Danielle E Anderson ⁵ , Yi-Hao Chan ⁶ , Rachael Pung ⁷ , Cheryl Sy Heng ⁸ , Li Wei Ang ⁹ , Adrian Kang Eng Zheng ⁵ , Bernett Lee ¹⁰ , Shirin Kalimuddin ¹¹ , Surinder Pada ¹² , Paul A Tambyah ¹³ , Purnima Parthasarathy ¹⁴ , Seow Yen Tan ¹⁵ , Louisa Sun ¹⁶ , Gavin Jd Smith ⁵ , Raymond Tzer Pin Lin ⁴ , Yee-Sin Leo ¹⁷ , Laurent Renia ⁶ , Lin-Fa Wang ⁵ , Lisa Fp Ng ⁶ , Sebastian Maurer-Stroh ¹⁸ , David Chien Lye ¹⁹ , Vernon J Lee ²⁰



Affiliations

• PMID: 33840632
• DOI: 10.1016/j.ebiom.2021.103319

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.

Keywords: COVID-19; Clade; D614G; SARS-CoV-2; Severity; Transmission.