Genetic risk for severe COVID-19 correlates with lower inflammatory marker levels in a SARS-CoV-2-negative cohort.
Clin Transl Immunology
; 10(6): e1292, 2021.
Article
in English
| MEDLINE | ID: covidwho-1258049
ABSTRACT
OBJECTIVES:
It remains unknown how inflammatory marker levels differ amongst individuals susceptible to coronavirus disease 2019 (COVID-19), prior to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the onset of the cytokine storm. We used genetic risk scores to model how susceptibility to severe COVID-19 correlates with baseline levels of 35 inflammatory markers, by testing their impact in a SARS-CoV-2-negative population cohort. Because of the established effects of age and body mass index on severe COVID-19 risk, we further considered how these variables interacted with genetic risk to affect inflammatory marker levels.METHODS:
We accessed data on 406 SARS-CoV-2-negative individuals as part of a UK population study. Multiplex electrochemiluminescence methods were applied to blood serum, and 35 inflammatory markers were assayed. Corresponding genotype data, alongside results from a large genome-wide association study of severe COVID-19, allowed us to construct genetic risk scores and to test their impact on inflammatory protein levels.RESULTS:
Our results revealed that a higher genetic risk for severe COVID-19 was associated with lower blood levels of interferon gamma (IFN-γ), vascular endothelial growth factor D (VEGF-D) and tumor necrosis factor alpha (TNF-α). Inflammatory profiles of those with high genetic risk increasingly diverge from the norm in association with age and obesity.CONCLUSION:
Our results support the theory that individuals at risk of severe COVID-19 have a deficient innate immunity marked by reduced levels of inflammatory markers at baseline, including IFN-γ, VEGF-D and TNF-α. We hypothesise that a secondary overactive adaptive immune response may subsequently explain the high levels of cytokines observed in SARS-CoV-2-positive COVID-19 patients.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Language:
English
Journal:
Clin Transl Immunology
Year:
2021
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS