Impaired peripheral oxygen delivery during submaximal exercise in adults with long Covid, 2026, Callum Thomas et al

[Mij]

Abstract

Long COVID (LC) is a multisystem condition that is linked to distinct pathologies including viral persistence, immunological dysfunction, endothelial damage, and mitochondrial dysfunction.

To date, limited research has assessed peripheral tissue hypoxia to better understand LC symptom exacerbation. Forty-six people with LC and 10 controls (CON) completed two submaximal cardiopulmonary exercise tests (CPETs), separated by 24-h. Near-infrared spectroscopy (NIRS)-derived signals from the left gastrocnemius muscle were continuously monitored before, during, and after 2-day incremental CPET.

CPET outcomes demonstrated impaired physical function on day 2 compared with day 1 for the LC cohort at rest and VT1. LC tissue saturation index (TSI%) remained elevated above rest for a shorter duration of exercise compared to CON on day 1 (2nd minute vs. 5th minute).

On day 2, this response worsened for LC (Rest vs. 1st exercise minute: 63 ± 5% vs. 65 ± 5%; p < 0.05); meanwhile, CON exhibited sustained TSI% elevation throughout exercise above rest (Rest vs. 12th exercise minute: 62 ± 5% vs. 67 ± 4%; p < 0.05). LC TSI% remained elevated above rest for a shorter duration of exercise compared to CON, worsening for LC on day 2. LC showed rapid normalization of TSI%, suggesting impaired muscle oxygenation and recovery during repeated exercise.
Study

 

[Murph]

Looks like something to me.

 

[Eleanor]

but limitations:

The variability in probe placement and unaccounted differences in adipose tissue thickness prevented valid between-group comparisons of TSI% in this study. Increased adipose tissue can distort NIRS signals, leading to an overestimation of TSI%. This occurs because the signal becomes more reflective of the adipose tissue, which typically has a higher TSI% compared to skeletal muscle due to its lower metabolic rate (Niemeijer et al., 2017). However, probe placement location between days was kept identical using an anatomical marker pen on day 1, which allowed for reliable comparisons between day for the same participant.

Additionally, the use of continuous-wave NIRS and the selection of the gastrocnemius muscle rather than the vastus lateralis employed in previous studies introduce further considerations regarding signal quality and interpretation. This study did not include biomarker analyses or additional assessment techniques to confirm endothelial damage or mitochondrial dysfunction, both of which have been hypothesized to impair oxygen delivery and contribute to abnormal energy metabolism and PESE/PEM.

Age matching was not applied to recruitment in this study, with the LC group significantly older than the CON group. It is possible that the worsened ventilatory responses observed for LC during incremental CPET may have been impacted by this factor (e.g., V̇E/V̇CO2 slope increases with age; Phillips et al., 2020), and this uncertainty could be resolved by recruiting similarly aged CON groups in future work.

 

[Utsikt]

No PEM:

Eligibility for the LC cohort was established via telephone screening and required a confirmed COVID-19 history, a clinical LC diagnosis consistent with the WHO definition (WHO, 2022), and the absence of moderate–severe PEM, assessed using the DePaul Symptom Questionnaire (DSQ; Cotler et al., 2018). Moderate–severe PEM was defined as reporting a 3 or 4 for symptom frequency and severity on the DSQ. Control participants were free from confounding comorbidities (e.g., chronic obstructive pulmonary disease, coronary artery disease, diabetes, etc.).

No age matching:

Age matching was not applied to recruitment in this study, with the LC group significantly older than the CON group. It is possible that the worsened ventilatory responses observed for LC during incremental CPET may have been impacted by this factor (e.g., V̇E/V̇CO2slope increases with age; Phillips et al., 2020), and this uncertainty could be resolved by recruiting similarly aged CON groups in future work.

It would be interesting to compare this data to the data of pwME/CFS with clear PEM. If the changes are the same, it might mean that they are less related to PEM.

 

[Mij]

From the author of this paper July 2025: Callum Thomas

Submaximal 2-day cardiopulmonary exercise testing to assess exercise capacity and post-exertional symptom exacerbation in people with long Covid



"A new peer-reviewed publication from our
research team has been released online which suggests problems with oxygen transport, usage or both may contribute to Long COVID symptoms".

"Using some carefully controlled, low level cycle exercise we showed a scientific reason for why those with Long COVID may struggle to exercise, with some data indicating issues with energy production as early as the first minute of the test and a worsening effect 24-hours later".

"We did not include those who were at a moderate-high risk for PEM but did find a way for those with low risk PEM to carefully participate, with only one adverse event reported."

 

[Eleanor]

No PEM:

[...]absence of moderate–severe PEM, assessed using the DePaul Symptom Questionnaire (DSQ; Cotler et al., 2018). Moderate–severe PEM was defined as reporting a 3 or 4 for symptom frequency and severity on the DSQ.

although, how reliable is the DSQ in measuring severity of PEM (and their choice of cutoff)?

 

[Utsikt]

although, how reliable is the DSQ in measuring severity of PEM (and their choice of cutoff)?

My impression is that it produces far more false positives than false negatives. But I don’t think we have good data on it.