Decreased Fatty Acid Oxidation and Altered Lactate Production during Exercise in Patients with Post-acute COVID-19 Syndrome, 2022, de Boer et al

[Andy]

To the Editor:

After acute infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many individuals experience a range of symptoms including dyspnea, exercise intolerance, and chest pain commonly referred to as “post–COVID-19 syndrome” or as post-acute sequelae of SARS-CoV-2 infection (PASC) (1). Exertional dyspnea and physical activity intolerance in PASC can be debilitating despite mild acute coronavirus disease (COVID-19) and normal resting pulmonary physiology and cardiac function (2). There is an urgent need to understand the pathogenesis of PASC and find effective treatments. The cardiopulmonary exercise test (CPET) is commonly used to investigate unexplained exertional dyspnea; as such, it could provide insight into mechanisms of PASC. CPET data can be used to calculate rates of β-oxidation of fatty acids (FATox) and of lactate clearance, providing insight into mitochondrial function (3). Fit individuals have better mitochondrial function and a higher rate of FATox during exercise than less fit individuals (4). Our results suggest that patients with PASC have significant impairment in fat β-oxidation and increased blood lactate accumulation during exercise, regardless of previous comorbidities.

Open access, https://www.atsjournals.org/doi/full/10.1164/rccm.202108-1903LE

 

[Hutan]

Just on the lactate question:



Figure 1B. From the left:
PASC with comorbidities
PASC without comorbidities
Metabolic syndrome
Healthy, moderately active

Measured using a catheter during CPET.

 

[Hutan]

Our data suggest abnormally low FATox and altered lactate production by skeletal muscle as a putative cause of—or contributor to—the functional limitation of patients with PASC. Normally, as glycolysis increases with exercise intensity, lactate is oxidized for fuel in mitochondria, mainly in adjacent slow-twitch muscle fibers. Like FATox, lactate clearance capacity is a useful surrogate for mitochondrial function.

In patients with PASC, even in those with normal pre–COVID-19 physical fitness and free of comorbidities, the metabolic disturbances of the skeletal muscle during exercise may be worse than those reported in moderately active individuals or in individuals with metabolic syndrome (3).

Whereas rising blood lactate levels are expected during high exercise intensity (as glycolytic flux exceeds the rate of mitochondrial pyruvate oxidation), a high blood lactate at lower exercise levels indicates mitochondrial dysfunction (7). The inappropriately high arterial lactate levels at relatively low exercise intensity (e.g., >9 mM at 150 W) in patients with PASC indicate that the transition from FATox to CHOox occurs prematurely, suggesting metabolic reprogramming and dysfunctional mitochondria.

 

[RobH]

One of the authors of this study just posted on Twitter:



2 years ago we published this study suggesting significant mitochondrial dysfunction in Long-Covid patients. The idea was so crazy that we weren't able to include "mitochondrial dysfunction" in the article title. Instead, we had to used "decreased fat oxidation and altered lactate production" as surrogates for mitochondrial function through the methodology that I developed. It as also such a wild idea that the journal didn't want to publish it as an article and instead it was just as a "correspondence" to the Editor. Link here

https://atsjournals.org/doi/10.1164/rccm.202108-1903LE?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed…

2 years later, there are dozens of very well articulated and sophisticated studies showing mitochondrial dysfunction in long-covid patients. The evidence now is quite robust. While we don't have any medication to treat mitochondrial dysfunction, exercise is the only method we know that can work. With so much evidence, it is time for hospitals and healthcare systems to invest in supervised exercise programs for long-covid patients. In my previous post, I showed a pioneer exercise intervention study led by my colleagues
@alberenguel
and
@ManoloGallango
at the
@HospitalUnivTO
in Spain where they showed that 8 weeks of supervised exercise training improved multiple parameters in Long-Covid patients.

 

[SNT Gatchaman]

The evidence now is quite robust. While we don't have any medication to treat mitochondrial dysfunction, exercise is the only method we know that can work. With so much evidence, it is time for hospitals and healthcare systems to invest in supervised exercise programs for long-covid patients

OK, but what if an abnormal response to exercise is the thing that causes or perpetuates mitochondrial dysfunction?