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While varnishing my furniture I thought more about this and am now more apprehensive about the risks of #BCG vaccination for Covid-19. Here's why (1/14) https://twitter.com/MycoLAtes/status/1248872807766818818
The idea behind BCG vaccination is to improve immunity against other pathogens by priming the innate immune response (so-called trained immunity). 2/14)
This is mostly done and measured in the studies by e.g. Netea's group by increased production of cytokines such as IL-1 and IL-6. See eg. (3/14). https://scholar.google.nl/scholar?hl=nl&as_sdt=0%2C5&as_vis=1&q=Netea+BCG+IL-6&btnG=#d=gs_qabs&u=%23p%3DLHzHtJe9xuoJ
See also this excellent paper by @MazDivangahi @E_v_a_Kaufmann @LB_Barreiro and others on the subject. 4/14 https://pubmed.ncbi.nlm.nih.gov/29328912/
This makes sense because those cytokines are associated with inflammation that usually helps with controlling viral infections (especially IL1) 5/14.
But in severe Covid-19 there is often excessive inflammation which may actually cause some of the most extreme symptoms (not sure yet! Research is ongoing worldwide). 6/14
Therefore there are multiple clinical trials ongoing with inhibition of IL-6, the IL-6 receptor, or IL-1. Sometimes even combinations, like here 7/14: https://clinicaltrials.gov/ct2/show/NCT04330638
So on the one hand we're increasing the levels of these cytokines and on the other hand decreasing them. Is that not insane? 8/14
Well, maybe... But the immune system is lifes most complex balancing act. It may protect people to have high levels of these cytokines from becoming ill. In a small part of the people, too high levels of these cytokines could cause increased pathogy. 9/14
What the optimal balances of these things are, is incredibly hard to say and study and will likely require years of study. 10/14
So this is my take on what Dr Uhrdall (whose science I respect tremendously) has probably thought, to lead him to the conclusions in the interview linked at the top of this thread. 11/14
Now I'm sure that the great scientists and clinicians running the trial in the Netherlands ( @MarcBonten and @MihaiNetea), have thought about all this and will monitor the risks carefully. 12/14
But I hear quite some people mentioning that it is definitely a safe approach even though it is unsure that it will work. The article with Dr Uhrdall has at least made me realize, that it may once again not be that simple.. 13/14
The trials are ongoing both with BCG and with cytokine inhibitors. These trials will be hugely important in our understanding of the disease pathogenesis and may also be important for the vaccine trials following them. 14/14
15/14 so I'm sure I'm not the only one who was thinking along these lines. Am I missing something? Please share what.
