Genetic Variants Mimicking IL-6 Receptor Blockade May Be Associated With Lower Hospitalization Risk in COVID-19

DNA strands
DNA strands
Genetic variants mimicking therapeutic inhibition of the IL-6 receptor may be associated with lower hospitalization risk in COVID-19.

Genetic variants mimicking therapeutic inhibition of interleukin (IL)-6 receptor signaling may be associated with a lower risk for hospitalization in coronavirus disease 2019 (COVID-19), according to correspondence published in Lancet Rheumatology.

Inhibition of IL-6 receptor has been indicated as one of the potential therapeutic strategies for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; several clinical trials have been conducted to assess the efficacy of tocilizumab and sarilumab against SARS-CoV-2 infection.

Recently, a genetic instrument that included 7 genetic variants in or adjacent to the IL-6 receptor was found to have a similar effect in COVID-19 as pharmacologic IL-6 receptor inhibitors. Authors of this correspondence aimed to determine whether these genetic variants had an effect on the risk for hospitalization in COVID-19 and other SARS-CoV-2-related outcomes.

The IL-6 receptor variants were found to be associated with lower serum C-reactive protein (CRP) concentrations, lower risk for rheumatoid arthritis (odds ratio [OR], 0.93 per 0.1 standard deviation lower CRP; 95% CI, 0.90-0.96; P <.0001), coronary heart disease (OR, 0.96; 95% CI, 0.95-0.98; P <.0001), and hospitalization due to COVID-19 (OR, 0.88; 95% CI, 0.78-0.99; P =.03).

Furthermore, compared with a population-based control group, IL-6 receptor genetic variants were also associated with decreased risk for SARS-CoV-2 infection (OR, 0.92; 95% CI, 0.89-0.95; P <.0001), but there was no difference in the risk for mortality or need for respiratory support.

“Our results serve as genetic evidence for the potential efficacy of IL-6 receptor blockade in COVID-19 and support the study of IL-6 receptor inhibitors in randomized controlled trials,” the authors concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Bovijn J, Lindgren CM, Holmes MV. Genetic variants mimicking therapeutic inhibition of IL-6 receptor signaling and risk of COVID-19. Lancet Rheumatol. Published online September 25, 2020. doi:10.1016/S2665-9913(20)30345-3