Endothelial dysfunction is the key of long COVID-19 symptoms: The results of TUN-EndCOV study

Abstract

Background The COVID-19 disease is a multisystem disease due to in part to the vascular endothelium injury. Lasting effects and long-term sequalae could persist after the infection and may be due to persistent endothelial dysfunction. Purpose Our study focused on the study of endothelial function measurement by digital thermal monitoring (DTM) of endothelial quality index with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long COVID-19 symptoms are due to endothelial dysfunction. Methods This is a prospective multicenter longitudinal observational cohort study. Endothelial function was evaluated with “E4-Diagnose” Polymath Tunisia based on the Endothelium Quality Index (EQI). A complete echocardiographic evaluation analysis was performed. Primary outcomes were defined as the occurrence of long COVID-19 symptoms in patients with endothelial dysfunction measured by EQI. Results A total of 798 patients were included in this study. Patients were included at an average time of 68.93 ± 43.1 days. The mean EQI was 2.02 ± 0.99 [0–5]. A total of 397 (49.7%) patients had poor or very poor EQI and 211 (26.4%) patients had very poor EQI. The median age was 49.94 ± 14.2 (18–80) years. A total of 618 patients (77.4%) had long COVID-19 symptoms. Patients with long COVID-19 symptoms had a reduced EQI (1.99 ± 0.97 vs. 2.09 ± 1.05, P = 0.24). Among long COVID-19 symptoms, fatigue was the most common symptom reported in 42.2%. Fatigue and chest pain were significantly associated to the endothelial dysfunction ( P = 0.04 and 0.001 respectively). Patients with chest pain had significantly lower EQI (1.74 ± 1.0 vs. 2.09 ± 0.9, P ≤ 10 −3 ) and LVGLS (−16.35 ± 3.0 vs. −17.16 ± 2.5, P = 0.04). Conclusion Long COVID-19 symptoms specifically chest pain and fatigue are due to persistent poor endothelial quality index. These findings allow a better care of patients with long COVID-19 symptoms.

Psychophysiologic symptom relief therapy (PSRT) for post-acute sequelae of COVID-19: a non-randomized interventional study

“…The etiology of symptoms for patients with PASC who had mild/moderate disease without evidence of organ injury by traditional clinical testing remains elusive. There have been a number of reports on the potential etiologies of PASC including capillary microclots (11), viral reservoirs in the gut (12), low cortisol levels (13), mitochondrial dysfunction (14), endothelial dysfunction (15), subtle changes on cardiac MRI (16), autoimmune reactions (6), and presence of a persistent virus/spike protein (17). In contrast to these reports, Sneller et al examined 186 adults at least 6 weeks after laboratory-confirmed COVID-19 infection and found no evidence of persistent viral infection, autoimmune reaction, or abnormal immune activation (6).…”

“…We previously proposed and tested the hypothesis that some forms of chronic pain in which a specific physiological etiology for the pain is unclear, such as chronic back pain, represent a psychophysiological process (19,20). Our scientific premise, based on initial encounters with PASC patients without organ injury and an assessment of the literature (see discussion), is that patients with mild-moderate initial COVID-19 infections without identifiable organ injury could potentially be suffering from a psychophysiologic process developed during or shortly after acute infection (15)(16)(17)(18). Our psychophysiologic intervention in back pain patients significantly reduced back pain across multiple metrics; therefore, we hypothesized that a modified version of this intervention (Psychophysiologic Symptom Relief Therapy, PSRT) would attenuate symptoms in PASC patients across multiple health symptom domains.…”