Tuesday, March 31, 2020 11:10:00 AM
Commentary on cytokine storm in COVID19:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext
Interesting article on cytokine storm, which tends to be what kills in COVID19:
https://www.uab.edu/reporter/know-more/publications/item/8909-here-s-a-playbook-for-stopping-deadly-cytokine-storm-syndrome
Some people have different genetics of the perforin pathway, and are more prone to hyperinflammatory responses / cytokine storm.
Hopefully some of these immunomodulatory therapies (IL-6 antibodies, immunomodulatory stem cells, CCR5 antibodies - see CYDY - wow, human defensin mimetics like brilacidin) will be able to dampen down the cytokine storm in COVID-19.
CYDY's CCR5 blocker seems to prevent macrophage migration to the site of inflammation, preventing the macrophage induced cytokine storm.
Some of Cron's previous papers on CSS/CRS/MAH/HLH:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004271/
https://www.frontiersin.org/articles/10.3389/fimmu.2019.00119/full
A robust immune response is desirable at the initial stages of infection, but it is the hyperimmune inflammatory response that kills in the end.
Here is a nice commentary on immune response in COVID-19:
https://www.nature.com/articles/s41418-020-0530-3
That is where anti-IL6, (activated) MSCs/MAPCs, and other anti-inflammatory or immunomodulatory (anti-CCR5) strategies come in.
Three immune-related things predict death: (1) high IL-6, (2) high serum ferritin, and (3) lymphocytopenia. The first two are the cytokine storm from active macrophages, and the third of unknown cause. It's possible the cytokine storm causes lymphocytopenia (possible cause #3 from paper below).
Here is a very nice paper (pre-print) on lymphocytopenia being a predictor of poor outcome:
https://www.medrxiv.org/content/10.1101/2020.03.01.20029074v1.full.pdf
We definitely need more data on which drugs work, and what is happening with the immune response to SARS-CoV-2 in patients that successfully fight it off versus those that don't.
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