Thread by @ZdenekVrozina

An interesting and biologically plausible pilot study that provides a fairly strong signal that pediatric Long COVID may be associated with impaired microcirculation and increased arterial stiffness🧵

The study builds on earlier adult research suggesting that persistent symptoms after COVID may be linked to capillary loss and endothelial dysfunction.
This was an observational comparative cohort study, not a randomized or interventional trial.

The study included 37 pediatric patients with Long COVID and 46 healthy controls. On average, the patients were evaluated about 206 ± 167 days after a positive test, so often many months after the initial infection.

Most were adolescents. The average age in the LC group was 13.5 years. The most common symptoms were headache, reduced exercise tolerance, fatigue, and shortness of breath.

The patients were recruited from a specialized LC clinic, so they were not a random sample of all children who had COVID. This raises the possibility that the study captured a more symptomatic or more complex subgroup than the average child after infection.

The first method was sublingual SDF imaging, which looks at the tiny blood vessels under the tongue. They measured
MFI = quality of microvascular blood flow
TVD = total vessel density
PPV = proportion of perfused vessels
distribution of vessels by size

The second was EndoPAT, which provides indirect measures of
RHI as a marker of endothelial function
AIx@75 as a marker of arterial stiffness

Microcirculation
Compared with controls, children with Long COVID had
lower MFI
lower TVD
lower PPV
In simple terms, this suggests fewer small vessels and poorer perfusion.

The most pronounced changes were seen in the small vessel compartment, meaning the capillary side of the microcirculation. At the same time, the relative proportion of medium and large vessels was higher, which the authors interpret as a possible redistribution

Small-vessel TVD 4.61 vs 9.53 mm/mm²
small-vessel PPV 4.00% vs 9.21%
proportion of small vessels 29.97% vs 49.08%
Most of these differences were highly statistically significant!

Arterial stiffness
The LC group also had a higher AIx@75, which points to increased arterial stiffness. By contrast, RHI, the marker of endothelial reactivity, did not differ significantly between groups.
So the clearest signal was in microcirculation and arterial stiffness, but not in this particular endothelial function measure.

The differences remained significant even after statistical adjustment for age, BMI, blood pressure, and sex.

What is the significance of the findings in children with shortness of breath?
This is probably the most clinically interesting part of the paper. Children with shortness of breath had an even lower proportion of small vessels than children with Long COVID without dyspnea. The clearest association was mainly with capillary rarefaction.

The study fits well with the hypothesis that Long COVID may be (at least in part) a vascular and microvascular disorder. The authors mention several possible mechanisms
viral persistence or persistence of viral components
post-acute inflammation
autoimmunity
thrombotic processes
endothelial dysfunction
mitochondrial dysfunction

The control group was examined before the pandemic. That helps avoid the problem of unnoticed prior SARS-CoV-2 infection.

One of the key limitations?
No post COVID without Long COVID comparison group. Without that group, it is hard to know whether these vascular changes are truly specific to Long COVID, or whether some of them might occur more broadly after infection.

There was no long-term follow-up. We do not know whether the microcirculatory changes improve, worsen, or resolve over time.

The authors themselves state that impaired microcirculation and increased arterial stiffness may predispose patients to a higher long-term risk, for example of hypertension or atherosclerosis. @szupraha @ZdravkoOnline @adamvojtech86 @adamkova_vera @strakovka

Boever at al., Microcirculatory impairment and increased arterial stiffness in pediatric Long COVID patients. link.springer.com/article/10.100…