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