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1/n I am asked on a daily basis about IL-6 blockade in #COVID19 patients @sloan_kettering . The truth is that I don't know if this intervention is helpful, neutral, or harmful. Colleagues point to the role of IL-6 blockade in treating CAR T cell toxicities and its cytokine storm.
2/n In the CAR T cell setting, IL-6 is clearly pathological and the IL-6 levels observed are typically far higher (10x or more) than those in critically ill COVID19 patients. It is not at clear to me that this concept is applicable to COVID. Why? There are important differences
3/n between a viral infection and genetically engineered T cells that causes a sterile inflammation. First, your immune system needs IL-6 to stimulate T follicular helper cells to foster Ab responses. This is likely to be important in generating sterilizing humoral (Ab-mediated)
4/n immunity against COVID. This line of thinking does not apply to CAR T cells. Second, loss of IL-6 signaling is detrimental in animal models of viral infections (VSV, LCMV). This review sums up recent studies and points out that IL-6 may be beneficial in some settings and
5/n pathological in others. Context matters. When asked, I simply say that I don't know. I'd rather accept my lack of knowledge than promote a false sense that I know the answer and can intuit which patients may benefit from IL-6 blockade. https://www.frontiersin.org/articles/10.3389/fmicb.2019.01057/full
6/n The truth is that we need to study this question quickly and decisively in a way that gives us a clear answer. It is OK to acknowledge these uncertainties to ourselves and to our patients, even as we struggle to provide the best care possible today. https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments
