Comparison of the muscle oxygenation during submaximal and maximal exercise tests in patients post-[COVID-19]... 2024 Başak Kavalcı Kol et al

[Andy]

Full title: Comparison of the muscle oxygenation during submaximal and maximal exercise tests in patients post-coronavirus disease 2019 syndrome with pulmonary involvement

ABSTRACT

Introduction
Pulmonary involvement is prevalent in patients with coronavirus disease 2019 (COVID-19). Arterial hypoxemia may reduce oxygen transferred to the skeletal muscles, possibly leading to impaired exercise capacity. Oxygen uptake may vary depending on the increased oxygen demand of the muscles during submaximal and maximal exercise.

Objective
This study aimed to compare muscle oxygenation during submaximal and maximal exercise tests in patients with post-COVID-19 syndrome with pulmonary involvement.

Methods
Thirty-nine patients were included. Pulmonary function (spirometry), peripheral muscle strength (dynamometer), quadriceps femoris (QF) muscle oxygenation (Moxy® device), and submaximal exercise capacity (six-minute walk test (6-MWT)) were tested on the first day, maximal exercise capacity (cardiopulmonary exercise test (CPET)) was tested on the second day. Physical activity level was evaluated using an activity monitor worn for five consecutive days. Cardiopulmonary responses and muscle oxygenation were compared during 6-MWT and CPET.

Results
Patients’ minimum and recovery muscle oxygen saturation were significantly decreased; maximum total hemoglobin increased, heart rate, blood pressure, breathing frequency, dyspnea, fatigue, and leg fatigue at the end-of-test and recovery increased in CPET compared to 6-MWT (p < .050). Peak oxygen consumption (VO2peak) was 18.15 ± 4.75 ml/min/kg, VO2peak; percent predicted < 80% was measured in 51.28% patients. Six-MWT distance and QF muscle strength were less than 80% predicted in 58.9% and 76.9% patients, respectively.

Conclusions
In patients with post-COVID-19 syndrome with pulmonary involvement, muscle deoxygenation of QF is greater during maximal exercise than during submaximal exercise. Specifically, patients with lung impairment should be evaluated for deoxygenation and should be taken into consideration during pulmonary rehabilitation.

Paywall, https://www.tandfonline.com/doi/full/10.1080/09593985.2024.2327534

 

[Hutan]

Thanks to a member for access.

A Turkish team

Thirty-nine patients with post-COVID-19 syndrome with pulmonary involvement (Centers for Disease Control and Prevention, 2023) were recruited for the study. Pulmonary involvement of the patients was determined by a pulmonologist according to CT (Lizzi et al., 2022). Patients who had at least 12 weeks after diagnosis and had long-term symptoms were included in the study.

So, the question I have is how relevant is this to ME/CFS type illness. In the introduction the authors seem to be suggesting that the long-term (ME/CFS-type) symptoms are associated with ground glass opacities in the lungs.

Long-term symptoms include fatigue, dyspnea, impaired exercise capacity, and lung function; however, the symptoms are not lim- ited to only these (Nalbandian et al., 2021; Raman et al., 2021). All these symptoms are associated with wide- spread ground glass opacities on computed chest tomo- graphy scans and radiography (Kang, Li, and Zhou, 2020; Toussie et al., 2020). It is essential to understand the physiological mechanisms underlying persistent dyspnea, fatigue, and impaired exercise capacity after COVID-19 infection to develop appropriate rehabilitation interven- tions to improve these symptoms.

The 6-MWT was performed to evaluate the patients’ muscle oxygenation and cardiorespiratory responses during the submaximal exercise test, and CPET was performed to evaluate the responses during the maximal exercise test. The evaluations of the patients were com- pleted in two days. Muscle oxygenation during the 6-MWT and CPET on two different days were mea- sured and compared. The patients were evaluated by different, experienced specialist physiotherapists on the first and second days. On the first day, demographic and clinical characteristics, post-COVID-19 functional sta- tus scale (PCFS), QF muscle strength, and 6-MWT were investigated, and on the second day, CPET was per- formed. Activity monitor to measure physical activity was worn on each patient for five consecutive days end of the second day.

Uses a measure of functional status limitations:

The functional status of individuals was graded using the PCFS whose validity (r = 0.534, p < .001) and relia- bility (intraclass correlation coefficient (ICC): 0.734– 0.880) have been established (Çalık Kütükcü et al., 2021; Klok et al., 2020). The PCFS test and retest scores have a Cronbach’s alpha value of 0.821, indicating that this scale is reliable (r = 0.707, p < .001) (Çalık Kütükcü et al., 2021). According to the functional status limita- tion of the PCFS scale: grade 0 (no), grade 1 (negligible), grade 2 (slight), grade 3 (moderate), grade 4 (severe), and grade 5 (death) (Sacristán-Galisteo et al., 2022).

Nice to see the use of an activity monitor after the CPET. Also some effort to cut out some of the noise in CPET results:

Participants were asked to avoid physical activities for 24 hours before CPET and to avoid alcohol, caffeine, and other stimu- lants and food for at least 8 hours before the evaluations.

Muscle oxygen saturation was measured using a near-infra red spectroscopy system

Quadriceps femoris muscle oxygen and THb level were measured before the CPET and the 6-MWTs at rest, during, and after the test in first- minute recovery.

 

[Hutan]

The majority of our patients had mild (38.5%) and moderate (48.7%) functional limitations, according to PCFS.

Mean number of steps/day = 5679 SD 3332

Desaturation was observed in 22 (56.4%) patients during 6-MWT and 16 (41%) patients during CPET.

This study found that post-COVID-19 patients with pulmonary involvement had lower skeletal muscle oxy- gen saturation at the microcirculatory level than sub- maximal during maximal exercise testing, which may contribute to exercise intolerance.

(sic)

In addition, total hemoglobin was found to be higher during CPET compared to 6-MWT. This may be related to an increase in the amount of total hemoglobin due to a proportional increase in blood flow velocity in the upstream and downstream vessel blood (Laughlin et al., 2012) to increase oxygen delivery to the muscles during maximal exercise.

(Sorry, I've run out of steam)

 

[SNT Gatchaman]

Muscle oxygen saturation was measured using a near-infra red spectroscopy system

This is the Moxy system which is a commercial wearable NIRS device being used for athlete training (it's not cheap). Here is a relevant recent paper which could stay linked in this thread —

Comparing the reliability of muscle oxygen saturation with common performance and physiological markers across cycling exercise intensity
Yogev, Assaf; Arnold, Jem; Nelson, Hannah; Clarke, David C.; Guenette, Jordan A.; Sporer, Ben C.; Koehle, Michael S.

Wearable near-infrared spectroscopy (NIRS) measurements of muscle oxygen saturation (SmO2) demonstrated good test-retest reliability at rest. We hypothesized SmO2 measured with the Moxy monitor at the vastus lateralis (VL) would demonstrate good reliability across intensities. For relative reliability, SmO2 will be lower than volume of oxygen consumption (VO2) and heart rate (HR), higher than concentration of blood lactate accumulation ([BLa]) and rating of perceived exertion (RPE).

We aimed to estimate the reliability of SmO2 and common physiological measures across exercise intensities, as well as to quantify within-participant agreement between sessions. Twenty-one trained cyclists completed two trials of an incremental multi-stage cycling test with five-minute constant workload steps starting at 1.0 watt per kg bodyweight (W∙kg-1) and increasing by 0.5 W∙kg-1 per step, separated by one-minute passive recovery intervals until maximal task tolerance. SmO2, HR, VO2, [BLa], and RPE were recorded for each stage. Continuous measures were averaged over the final 60 seconds of each stage. Relative reliability at the lowest, median, and highest work stages was quantified as intraclass correlation coefficient (ICC). Absolute reliability and within-subject agreement were quantified as standard error of the measurement (SEM) and minimum detectable change (MDC).

Comparisons between trials showed no significant differences within each exercise intensity for all outcome variables. ICC for SmO2 was 0.81-0.90 across exercise intensity. ICC for HR, VO2, [BLa], and RPE were 0.87-0.92, 0.73-0.97, 0.44-0.74, 0.29-0.70, respectively. SEM (95% CI) for SmO2 was 5 (3 - 7), 6 (4 - 9), and 7 (5 - 10) %, and MDC was 12, 16, and 18%. Our results demonstrate good-to-excellent test-retest reliability for SmO2 across intensity during an incremental multi-stage cycling test. VO2 and HR had excellent reliability, higher than SmO2. [BLa] and RPE had lower reliability than SmO2.

Muscle oxygen saturation measured by wearable NIRS was found to have similar reliability to VO2 and HR, and higher than [BLa] and RPE across exercise intensity, suggesting that it is appropriate for everyday use as a non-invasive method of monitoring internal load alongside other metrics.

Link | PDF (Frontiers in Sports and Active Living) [Open Access]

 

[SNT Gatchaman]

I think this team started off with patients with clear evidence of lung injury (mild-moderate changes on CT with the majority less than 50% involved lungs), a minority having required ventilation acutely. As Hutan says, not directly comparable to our typical ME-phenotype LC situation. They confirmed abnormal lung function, as you might expect. However the findings may indicate problems distinct from (or at least not directly related to) the lung injury. I wonder if the findings could be correlated with other recent Long Covid muscle findings.

To our knowledge, this is the first study to compare muscle oxygen saturation and total hemoglobin in skeletal muscle during submaximal and maximal exercise.

I'll re-order some of the sentence structure in their following quotes to make it easier to follow.

This study found [...] lower skeletal muscle oxygen saturation at the microcirculatory level during maximal exercise testing compared with submaximal exercise testing [...] which may contribute to exercise intolerance.

muscle oxygen saturation recovery was better at submaximal exercise intensities.

Decreased muscle oxygen saturation may be due to [..] two different physiological changes. First, capillary flow disturbances after COVID-19 infection limit oxygen transport in the lungs and tissues and can, therefore, cause hypoxemia and tissue hypoxia

So they suggest the lungs might be causing a problem via simple hypoxaemia

Second, the decrease in mitochondria function in the muscles may impair muscle oxygen transport and reduce muscle oxygenation.

So here, they're suggesting there may be a separate problem in the muscles and their mitochondria (which relates to Wüst et al)

Muscle oxygenation decreased during both the maximal and submaximal exercise tests; however, the difference in maximum to minimum muscle oxygenation during the test was more significant in the maximal exercise.

HR recovery response was better after the maximal exercise than the submaximal test, while the muscle saturation recovery response was worse. This situation may show that cardiac system responses are good and peripheral oxygen extraction responses are poor in recovery after exercise in patients with post-COVID-19 syndrome.

To our knowledge, available evidence suggests that cardiac output is maintained. Still, peripheral oxygen extraction is decreased in survivors of COVID-19, suggesting an impairment in oxidative metabolism resulting from this disease.

Problems with peripheral oxygen extraction have been highlighted by Systrom et al (which they indeed reference in the passage above).

Decreased muscle oxygen saturation may be associated with pulmonary and peripheral muscle impairment. In particular, in post-COVID-19 syndrome patients with pulmonary involvement, measuring peripheral oxygen saturation with a pulse oximeter does not accurately detect hypoxia. Therefore, muscle deoxygenation and the effects of a variety of exercise training on the muscle oxygen responses of the patients should be evaluated during exercise.

 

[SNT Gatchaman]

I would like to see the Moxy system applied to acutely mild/asymptomatic patients, like the Wüst cohort. However, more than just evaluating response to exercise as in this paper, I'm interested to see what happens with variations day-to-day. I wonder whether on bad days where my leg muscles feel "lactic" and fatigued there might also be a measurable difference in SmO2, perhaps part of PEM. So I'm tempted to see if I can get my hands on a Moxy device and do a little pilot trial with me and @Kiwipom vs our respective healthy age/sex-matched friends.

 

[Hutan]

Sounds very good @SNT Gatchaman. That loss of power that happens sometimes really does feel like inadequate oxygen, it's just like what happens at high altitude.

I see you found the paper in this thread - another one of those studies done decades ago.
Impaired oxygen delivery to muscle in chronic fatigue syndrome, 1999, McCully and Natelson

I've added the tag 'study idea' - might make it easier next time someone asks 'what should be studied?'