No signs of mast cell involvement in long-COVID: A case–control study, 2024, Lenning et al.

No signs of mast cell involvement in long-COVID: A case–control study
Ole Bernt Lenning; Grete Jonsson; Tore Grimstad; Emiel A. M. Janssen; Geir Sverre Braut; Frode Berven; Roald Omdal

Long-COVID caused by SARS-CoV-2 infection has significant and increasing effects on human health worldwide. Although a unifying molecular or biological explanation is lacking, several pathophysiological mechanisms have been proposed. Involvement of mast cells—evolutionary old “multipurpose” innate immune cells—was reported recently in studies of acute infection and post-acuteCOVID-19 syndrome. Mast cell activity has been suggested in long-COVID.

In this case–control study, we compared data from 24 individuals with long-COVID (according to the NICE criteria) and 24 age-and sex-matched healthy individuals with a history of SARS-CoV-2 infection without developing sequelae. Serum levels of the proteases beta-tryptase (TPSB2) and carboxypeptidase (CPA3), which are mast cell specific, were measured using immunoassays. The values were compared between the two groups and correlated to measures of physical exertional intolerance.

TPSB2 and CPA3 levels were median (range) 26.9 (2.0–1000) and 5.8 (1.5–14.0) ng/mL, respectively, in the long-COVID group. The corresponding values in the control group were 10.9 (2.0–1000) (p = 0.93) and 5.3 (3.5–12.9) ng/mL (p = 0.82). No significant correlations between TPSB2 or CPA3 levels and scores on the ten physical subscales of SF-36, 3.1–3.10 were revealed.

We found no significant differences in the levels of mast cell activation markers TPSB2 and CPA3 between the long-COVID and control groups and no correlations with proxy markers of exercise intolerance. Mast cell activation does not appear to be part of long-term pathogenesis of long-COVID, at least in the majority of patients.

Link | PDF (Scandinavian Journal of Immunology) [Open Access]

 

Fatigue is allowed and understandable (even if though we don't actually understand it). All this other stuff: brain fog, pain, hypersensitivity; that's all disputed.

I guess.

 

I find it extremely disturbing and frustrating that despite extensive research we are still unable to confidently say whether ME/CFS is Post-Viral or not

 

What would then explain the odd reactions people are having to all sorts of things that they never had problems with before, and started soon after COVID? I don't know if mast cells made sense as an explanation for that, although it was a reasonable hypothesis, but this is definitely a common phenomenon in LC and it has zero explanation so far. Typically it's food but isn't restricted to it.

The issues seem similar to what is often labeled MCAS, and may have little to do with mast cells if this is reliable, but it's definitely a significant thing. There is zero doubt that this is a significant issue, but so far because of poor methodologies it's impossible to tell which %. Especially as they usually are time-limited and researchers rarely ask the right questions.

Unfortunately the participants don't seem to be representative of those odd intolerance/reactions that a subset with LC have, so it's possible that they just missed it simply because they did the equivalent of looking for loss of smell in a cohort that happened to have none or too few who either never did lose their smell, or regained it before tests/samples were taken.

This is becoming a growing and frustrating problem in that there is a wide range of problems but cohorts are always as generic as possible, mostly because they have no means to identify subsets, and therefore it's like studying a huge car crash on a highway, doing a random sampling of people involved and most of the time never including the few people who were involved in serious crashes, mostly including bystanders who just happened to be in a very sudden traffic jam, and concluding from this that car crashes are no cause for concern. It's quite absurd.

We're really still stuck at the metaphorical stage of various people poking blindly at an elephant and labeling various things as representative of the whole. It's incredibly frustrating watching those experts in action, they seem completely out of their depth and not because of personal flaws but because of systems that simply never bothered developing the necessary skills and resources for this type of problem.