Last week someone asked what Dr. Afrin thought about COVID-19 and the cytokine storm. We shared your question with him. Here is his answer:
"Nobody who knows me or my writings will be surprised to learn I have been suspecting for some time now that the "hyperinflammation" (a.k.a. the "cytokine storm") which unfortunately seems to be the principal feature in the later stages of those with Covid-19 infection who suffer more serious courses of the illness might be arising -- perhaps not in all in such patients, but in "at least some" to "perhaps many" -- either directly or indirectly due to a mast cell activation syndrome (MCAS) which, more likely than not, was already present long before the infection came along.
I feel it's important to add as a sidebar at this point that I know it's been presented as "mysterious" that many Covid infected patients have been described as "previously healthy" and yet still are getting so ridiculously sick from this virus, but I've learned the hard way that many MCAS patients, too, have been described (indeed, often even have long taken to describing themselves) as "healthy" and that such a descriptor often belies the assortment of symptoms the patient in truth has long been having but has learned to tolerate/dismiss/ignore (or even self-treat) for various reasons we can all easily imagine, so you'll have to pardon me for wondering how accurate these descriptions of "previously healthy" actually are.
I would imagine that the doctors in the emergency rooms and in the hospitals, who are being overwhelmed taking care of these very sick patients simply don't have the time to delve much into the patient's history, extracting reports of symptoms the patient in truth has long been experiencing but also long ago stopped reporting/volunteering after learning that, for various reasons, such complaints were going to get the patient nowhere. Instead, the doctors just take it as gospel from the patient's chart, or even from the patient himself/herself, that he/she was "previously healthy" and move on to attending to higher priority matters. And thus, without a full backstory on the patient, it gets assumed by at least the doctor, and again sometimes even the patient, too, that the patient indeed was "previously healthy" when the truth is a good bit otherwise. See a few dozen patients with MCAS (let alone a few thousand, as I have) and you'll soon learn to question much of what's previously been assumed and written about a given patient who's now being suspected of having MCAS. Maybe most of what was said previously was accurate/correct -- and maybe parts of it were not and instead were just reported or recorded at the time as they were as a convenient shortcut when the doctor and/or the patient is pressed for time.)
At the same time, though, it must be acknowledged that there are certain aspects to the hyperinflammation of Covid-19 illness which are not well explained -- at least, not *directly* explained well -- by abnormal activation of the patient's *mast cells* (i.e., MCAS, not even severe MCAS) and instead are better explained by what ordinarily is a *much* rarer hyperinflammatory phenomenon called macrophage activation syndrome (MAS) -- though it's certainly not necessarily the case that it's an "either/or" situation with a severely ill Covid-infected patient having "either MCAS *or* MAS" and instead it's easily possible (pure conjecture at this point on my part, but nevertheless easily *possible*) that there is some curious aspect of the interaction between the Covid-19 virus and mast cells (normal or abnormal) which sparks the end-stage MAS. There even are aspects to the Covid hyperinflammatory syndrome which are not well explained by MCAS or MAS and *may* be due to yet other mechanisms.
So, yes, it's *possible* -- especially so given present best estimates of the substantial prevalence of MCAS -- that (almost always previously unrecognized/undiagnosed/untreated/uncontrolled) MCAS, by being "triggered" by the virus to "flare" to a more activated state, *might* be a key factor in the "inappropriate" progression of Covid-19 infection from a mild-moderate illness to a severe illness, and it's *possible* that MAS, too, might either emerge on its own or as an additional complication of flaring of MCAS. But let's get real here: at present these are merely hypotheses, without a single shred of *actual research findings* to support them. There's just been no research at all -- none, zero, zilch, nada -- into the interactions of the Covid-19 virus with MCAS. Importantly, note I am *not* saying that we don't know whether Covid-19 causes mast cell activation. Of course the Covid-19 virus causes mast cell activation. There's already at least one peer-reviewed published paper on that, but even without a published paper on that, we'd already know this to be a fact because we've *long* known that mast cells *normally* react to infections (including viral infections) of all types. That's what mast cells are *supposed* to do. So, the issue isn't *whether* mast cells are reacting to this virus. Rather, the issue is whether the mast cells in the individual patient's body are reacting *normally/appropriately* to this virus. And *maybe* the patient's *normal* mast cells indeed are reacting *normally* to this virus -- and *maybe* it's the case that it's just the (again, likely previously unrecognized/undiagnosed/untreated/uncontrolled) *abnormal* mast cells in an MCAS patient which are reacting *abnormally* to this virus. But, again, these are just interesting hypotheses, and it's going to need hard research to sort it all out -- though nobody who knows how little appreciation of mast cell activation disease (especially MCAS and its prevalence) there presently is in the medical profession at large will be surprised if such research doesn't get done for a long time to come (if ever). And if it gets done, this (challenging!) research almost certainly will get done at the major academic medical centers which have the sophisticated biomedical research resources needed to do this sort of work.
Finally, the question about whether imatinib might be helpful in Covid-19 infection might as well be expanded to a much more generic question as to whether *any* drug which has been shown helpful in at least some MCAS patients (and, for that matter, in MAS patients) might be helpful, at least at some point, in (at least some) Covid-infected patients with known or suspected MCAS. (Note that -- at least here in the U.S. -- imatinib is an extraordinarily expensive drug, and there's simply no way (yet) to know whether far less expensive drugs might serve the patient just as well as imatinib.) Again, though, we just don't have the research to know the answer to this question of therapeutic utility (vis-a-vis Covid infection) with regard to *any* of the drugs already found helpful in various MCAS or MAS patients. Yes, a few such drugs actually are being tested in Covid-19 clinical trials right now (and you can bet your bottom dollar that the researchers running those studies are not looking to see whether the subjects in those studies have MCAS), but the bottom line is that it's way too early right now to know with any meaningful degree of confidence which of these drugs (if any!) can be meaningfully helpful in Covid-infected patients with known or suspected MCAS (or any other Covid-infected patients, either, for that matter).
All I can tell people with interests in such matters is "Stay tuned..." And since this posting certainly isn't the place to go giving specific medical recommendations for individual patients, all I can say with regard to treatment of any patient with known or suspected MCAS who also unfortunately contracts a Covid-19 infection is that that treatment probably ought to "take into consideration" the patient's MCAS, but *specific*, *personalized* recommendations must be, well, *personalized* to the individual patient.
Anybody who knows MCAS even a little bit knows how differently the disease behaves in different MCAS patients; treatments which make sense to try in one patient might well be pointless (or even harmful!) in another. As always, if the local doctors attending to a patient with known or suspected MCAS would like to informally consult Dr. Dempsey or me regarding potential approaches to managing MCAS in the context of a Covid-19 infection, we will be happy to try to assist, and we merely request that the local doctor should *directly* reach out to us at our main office number (914-730-7390) to initiate a dialog.
MCAS itself -- let alone MCAS in the context of a Covid-19 infection -- is just far too complicated for us to try to have a technical medical discussion about it with the local doctor *via the patient*. It just won't work. There has to be *direct* doctor-to-doctor dialog, and for various reasons, it doesn't even work for the local doctor to ask the patient to ask us to call back to the local doctor. The local doctor himself/herself needs to *directly* reach out to us, and we make ourselves readily available to our colleagues who do so, to try to provide what assistance we can in the best spirit of professional collaboration."
-Dr. Lawrence Afrin
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