Altered tissue oxygenation in patients with post COVID-19 syndrome

Abstract

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 (-0.064 %/s) compared to CVD patients (-0.08 %/s) and healthy subjects (-0.145 %/s) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 0.84 %/s compared to CVD patients (1.04 %/s) and healthy controls (CG: 2.07 %/s) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors. Analyses of complications during acute infection, persistence of PCS symptoms (time after acute infection), or PCS severity (number of lead symptoms) as confounding factors did not reveal a significant effect.

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.

Keywords: COVID-19; Cardiovascular disease; Endothelial dysfunction; Microcirculation; Near-infrared spectroscopy.

Fig. 1

(A/B) Tissue oxygenation is altered in patients with Post COVID-19 Syndrome. (A) Changes of tissue oxygenation determined by near infrared spectroscopy (NIRS) before, during, and after standardized arterial occlusion. Inserts (A1) and (A2) show statistical comparison of linear regression slopes between patients with Post COVID-19 Syndrome (PCS), cardiovascular disease patients (CVD) and healthy controls during ischemia (3 min) and reperfusion. Respective linear regression slopes during ischemia are given as 1/slope for visualization indicating significantly slower oxygen consumption in PCS patients. (B) Comparison of tissue oxygenation before and after ischemia and reperfusion by tissue saturation index (TSI) between PCS and CVD patients and healthy controls. Individual data is presented with group mean and standard deviation. (C/D) Analyses of the effect of comorbidities on altered tissue oxygenation in PCS patients. (C) PCS patients were grouped by presence of arterial hypertension (HPT). Inserts (C1) and (C2) show statistical comparison of linear regression slopes between PCS patients (+) with (n = 18) and without (−) HPT (n = 12), and CVD patients during ischemia. Respective linear regression slopes during ischemia indicated significantly slower oxygen consumption in PCS patients with HPT compared to PCS patients without HPT and CVD patients. (D) PCS patients were grouped by BMI (≤/> median BMI = 31.0 kg ∗ m⁻²). Inserts (D1) and (D2) show statistical comparison of linear regression slopes between PCS patients with higher BMI compared to PCS patients with lower BMI and CVD patients during ischemia. Respective linear regression slopes during ischemia indicated significantly slower oxygen consumption in PCS patients with HPT compared to PCS patients without HPT and CVD patients. Data is presented as group mean values with 95 % confidence interval. Tissue saturation index was calculated as O₂Hb/(O₂Hb + HHb) × 100. P-values were calculated by comparison of linear regression slopes (in A, C, D) or one-way ANOVA corrected for multiple comparison (in B). ↓ start of ischemic phase (3 min), ↑ end of occlusion. ^#p < 0.05 for three-group comparison; *p = 0.01, ***p < 0.0001 for two-group comparison; ns, not significant.