Altered Tissue Oxygenation in Patients with Post COVID-19 Syndrome 2023 Schäfer et al

Andy

Retired committee member
For published version see
Altered tissue oxygenation in patients with post COVID-19 syndrome (2023, Microvascular Research)
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Pre-Print
https://www.researchgate.net/public...ation_in_Patients_with_Post_COVID-19_Syndrome

Background: Post COVID-19 syndrome (PCS) is a complex condition with partly substantial impact on patients’ social and professional life and overall life quality. Currently, the underlying cause(s) of PCS are unknown. Since PCS-specific symptoms could be associated with systemic alterations in tissue oxygen supply, we aimed to investigate changes in tissue oxygenation in patients with PCS.

Methods: A case-control study including 30 PCS patients (66.6 % males, 48.6 ± 11.2 years, mean time after (first) acute infection: 324 days), 16 cardiologic patients (CVD) (65.5 % males, 56.7 ± 6.3 years) and 11 young healthy controls (55 % males, 28.5 ± 7.4 years) was conducted. Near infrared spectroscopy (NIRS) was used to assess changes in tissue oxygenation during an arterial occlusion protocol on the non-dominant forearm (brachioradialis, 760/850 nm, 5 Hz). The protocol included 10-min rest, a 2-min baseline measurement followed by a 3-min ischemic period (upper-arm cuff, 50 mmHg above resting systolic blood pressure) and a 3-min reoxygenation period. PCS patients were grouped by presence of arterial hypertension and elevated BMI to assess the impact of risk factors.

Results: No differences in mean tissue oxygenation in the pre-occlusion phase existed between groups (p ≥ 0.566). During ischemia, comparisons of linear regressions slopes revealed slower oxygen desaturation for PCS patients (-3.8 %/min) compared to CVD patients (-4.8 %/min) and healthy subjects (-8.7 %/min) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 50.2 %/min compared to CVD patients (62.4 %/min) and healthy controls (CG: 124.2 %/min) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors.

Conclusions: This study provides evidence that the rate of tissue oxygen consumption is persistently altered in PCS and that PCS patients show an even slower decline in tissue oxygenation during occlusion than CVD patients. Our observations may at least partly explain PCS-specific symptoms such as physical impairment and fatigue.
 
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There isn't detail on PCS diagnostic criteria - just that there are persistent symptoms for more than 12 weeks. The PCS group have high levels of fatigue though (table 1).
Patients with an indication for medical rehabilitation based on a PCS diagnosis were consecutively recruited. Patients with a CVD diagnosis and no signs or symptoms of PCS were used as control group based on comparable reductions in exercise capacity (i.e. ∼70 % of age- and sex-adjusted reference).
Young healthy controls were included for comparison to unimpaired tissue oxygenation.

Mean time after (first) acute infection was 324 days (range: 75–774 days).

It looks as though efforts were made to reduce confounding factors e.g. measurement done in the morning, attention was given to the temperature of the room, caffeine and nicotine intake, and more.

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It's definitely interesting, but the control groups are small, there is no healthy post-infection control group of a similar age, and there is quite a complicated picture of Covid complications and medication use among the PCS and cardiac participants.

This study provides evidence that the rate of tissue oxygen consumption is altered in PCS patients. Using a standardized arterial occlusion protocol and continuous assessment of oxygenated hemoglobin by NIRS revealed, that PCS patients show an even slower decline in tissue oxygenation during ischemia at rest, compared to CVD patients. Our data suggest a persistently impaired systemic tissue oxygen consumption beyond an acute COVID-19 infection which may contribute to the described PCS symptoms, predominantly the severely reduced cardiovascular fitness and muscular weakness.

The paper suggests that the finding (both the slow decline in oxygenation after occlusion and the slow increase upon release) might be due to a reduced concentration of micro vessels and/or an issue with mitochondria.

I assume this sort of investigation would be easy to replicate. I hope the study is replicated.
Shame about the assumptions the researchers make about appropriate treatment:
Additionally, there is the need to identify appropriate interventions including exercise-based medical rehabilitation tailored to stimulate improved microcirculation and mitochondrial function.
 
Impaired oxygen consumption in tissues and in general may be based on two main and potentially synergistic physiological alterations. First, tissue concentration of microvessels may be reduced in PCS leading to a reduction in gas exchange. Second, a reduction in mitochondrial number or function could lead to a lower oxygen pressure gradient following recent findings that mitochondria represent an “oxygen sink” and that uncoupling of the mitochondrial respiratory chain leads to alterations in O2 gradients within the cellular microenvironment.

Ref is Mitochondria and oxygen homeostasis (2022, The FEBS Journal). Senior author is Paul Hwang (looking at WASF3 and HIF-1, endoplasmic reticulum stress, unfolded protein response etc). See this comment.
 
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