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Genetically proxied inhibition of interleukin-6 signaling: opposing associations with susceptibility to COVID-19 and pneumonia

By Susanna C Larsson, Stephen Burgess, Dipender Gill

Posted 18 Sep 2020
medRxiv DOI: 10.1101/2020.09.15.20165886

The inflammatory cytokine interleukin-6 (IL-6) is pivotal for orchestrating the immune response. Inhibitors of IL-6 signaling are being investigated as treatments for severe coronavirus disease 2019 (COVID-19). We conducted a Mendelian randomization study investigating the effect of IL-6 signaling on susceptibility to COVID-19 and pneumonia. Our results showed that genetically proxied inhibition of IL-6 signaling was associated with reduced risk of COVID-19, but also with increased risk of pneumonia. Respiratory disease is a main feature of severe COVID-19, and the potential of IL-6 signaling inhibitors to increase risk of pneumonia warrants vigilance and caution in their application to treat COVID-19.

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