Personalized Exercise Training Modulates Red Blood Cell Rheology and Morphology in Long COVID, 2026, Krüger et al.

[SNT Gatchaman]

Personalized Exercise Training Modulates Red Blood Cell Rheology and Morphology in Long COVID

Spoiler: Authors

Anna-Lena Krüger; Frederieke Schmidt; Wilhelm Bloch; Björn Haiduk; Marijke Grau

Long COVID is associated with persistent fatigue, exercise intolerance, and microcirculatory dysfunction. Altered red blood cell (RBC) rheology, including impaired deformability and increased aggregation, may contribute to these symptoms, yet the effects of exercise interventions remain unclear.

This longitudinal pilot study tested whether an individualized, symptom-responsive exercise program improves RBC rheology in Long COVID. A total of 170 (110 f/60 m) participants entered a five-phase training protocol; 15 completed all phases and formed a predefined finisher subgroup. RBC aggregation and deformability, hematological parameters, and coagulation- and iron-related markers were assessed across phases; RBC morphology was additionally analyzed in finishers at baseline and completion.

In the total cohort, aggregation indices decreased across training phases, accompanied by prolonged aggregation half-time, while hematological, coagulation, and iron markers remained largely unchanged. The deformability changes were not uniform in the full cohort; however, finishers showed a deformability shift after completion. Importantly, morphologically abnormal RBC decreased in finishers, and these changes correlated with deformability, suggesting that improved rheology is linked to reduced RBC abnormalities.

Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits.

Web | DOI | PDF | International Journal of Molecular Sciences | Open Access

 

[SNT Gatchaman]

In the context of Long COVID, exercise intolerance commonly manifests as an early onset of fatigue during physical activity, a reduced exercise capacity, and an exacerbation of symptoms after exertion, often described as post-exertional malaise (PEM).

This study investigated whether a software-guided, symptom-responsive personalized exercise intervention (TRIBAL) program modulates red blood cell (RBC) rheology in individuals with Long COVID.

“Finishers” are understood to be the participants who successfully completed the intervention program described below by the end of the observation period.

Total: 170 (110 F/60 M)
Finishers: 15 (6 F/9 M)

Attrition across training phases resulted in a small finisher subgroup; however, this was not driven by selection bias but rather reflected individual disease trajectories and symptom tolerance, underscoring the pronounced heterogeneity of Long COVID.

Finishers exhibited significantly lower aggregation index values and longer aggregation half-times at initial compared with the total cohort, alongside lower fibrinogen and D-dimer concentrations.

Finishers also exhibited a more favorable functional status at the baseline, as reflected by lower post-COVID-19 functional status scale (PCFS) scores compared with the total cohort, while post-COVID syndrome score (PCS) values were numerically but not statistically lower. Together, these findings are consistent with the evidence indicating that individuals with preserved functional capacity tend to display more favorable baseline rheological and coagulation profiles, which may support sustained participation in exercise-based interventions [38].

Importantly, finishers exhibited distinct baseline rheological and coagulation profiles and showed significant adaptations in RBC deformability and morphology during the intervention.

RBC deformability followed a different pattern. While no significant change was observed in the total cohort, finishers showed a significant reduction in deformability from initial assessment to post-phase 5, indicating a shift in RBC mechanical properties.

While the exploratory single-arm design and the lack of a control group limit causal inference, the study aimed to assess changes in impaired red blood cell rheology during individualized exercise-based rehabilitation under real-world conditions.

 

[Felis Catus]

Creating exercising programmes which can be completed by 15 ill people out of 170 is utterly appalling.
How many of them unharmed?

However, given the small finisher subgroup and the heterogeneity of Long COVID, the results should be interpreted with caution and require confirmation in larger controlled studies. If confirmed, personalized, software-guided exercise approaches such as the TRIBAL program may represent a scalable and accessible component of comprehensive rehabilitation strategies for Long COVID.

(my bold)

A candidate for funding from the National Decade Against Post-infectious Diseases.

God help us.

 

[SNT Gatchaman]

However, this study may be telling us something very useful about why exercise therapy doesn't work in the majority. It's probably worth looking closely at what the data on RBC deformability is showing. It's something that was identified very early on (1980s) and has come up in a number of ME and LC studies.

 

[wabi-sabi]

How many of them unharmed?

Potentially all, especially since they seemed to be the less sick ones to begin with. 15 finishers out of 170 starters is such a tiny number, it seems reasonable to me that this is the percentage of people post covid who can benefit from exercise. If they published their conclusion as less than 10% of long COVID patients benefit from exercise, I think I'd be interested in reading that paper.

What happened to the RBCs of the finishers? And why? can we make it happen to our RBCs? I can't understand the paper right now.

 

[Trish]

I've only read the abstract.

Is there a problem here of correlation being interpreted as causation the wrong way around? Maybe the finishers RBC's were on an improving trajectory anyway for reasons unrelated to exercise, and whatever that other reason was enabled them to complete the exercise program too.

 

[rvallee]

I think this is a secondary analysis from this trial: https://www.s4me.info/threads/indiv...nts-with-long-covid-2024-kieffer-et-al.47282/. Or something like it. It's in a reference for the description of the training program, where it says it's explained in this other paper. It's hard to say because I can't find the numbers of participants at end points in that other paper.

From the description of the program, I have no idea what is supposed to be personalized here other than participants could reduce or increase their effort:

The participants were asked to train at least twice weekly. Each exercise session consisted of 30 min. The first part always consisted of 15 min, and the second part followed a short break and covered the remaining 10–15 min. Each session was performed in groups of up to three people, with every participant receiving an individualized training regimen.

In the first part, the participants were asked to train on the M3i Total Body Trainer (Keiser GmbH, Coburg, Germany).

The Total Body Trainer (TBT) combines an indoor bike with a cross trainer, which allows both the upper and lower extremities to be simultaneously trained.

Moderately affected participants started with a medium resistance (e.g., gear 11, where 60 RPM corresponds to about 60 watts), while the more severely affected participants started with a low resistance (e.g., gear 5, where 60 RPM corresponds to about 30 watts).

The progression of the intensity during the study period was based on three criteria: (1) if the participants easily met the time target (15 min) and increased the speed to 60 RPM and beyond within the respective resistance/gear, (2) if the reports of previous sessions did not include the worsening of symptoms, and (3) when the participants reported that they could tolerate a higher intensity.

After a short break, in the second part (the remaining 10–15 min), the participants were instructed to perform breathing exercises or low-intensity strengthening, stretching, or mobility exercises mainly using their body weight or low-resistance devices (e.g., TotalGym RS Encompass PowerTower (TotalGym Europe B.V, Hoofddorp, The Netherlands), rubber bands, foam rolls, kettlebells, or elastic balls) depending on their capacity and (e.g., orthopedic) demands.

This is personalized in the same sense as pants are personalized, because they vary in size, fabric, color and so on. I guess, but this is just regular exercise. The whole thing where they try to infuse special awe into basic exercise is never not cringe. So much marketingspeech. There is simply no plausible reason to expect that any different form of generic exercise should make any difference in outcome, regardless of whether warm mud is involved.

 

[rvallee]

Prospectively, larger controlled studies are needed to confirm these results and to evaluate whether exercise-induced rheological improvements translate into functional and symptomatic benefits.

It started with 170 participants. How many do they want to qualify as larger? And how many would that require when they have a checks notes 9% completion rate?

There is zero reason to attribute those changes as being the result of the exercise program. In fact the relationship is more likely to be inverse. What is there to confirm, then? RBC deformability is something that has propped up a few times, but this is just mixing unrelated things in a desperate attempt to make exercise trials relevant.