Persistent capillary rarefication in long COVID syndrome.

BACKGROUND: Recent studies have highlighted Coronavirus disease 2019 (COVID-19) as a multisystemic vascular disease. Up to 60% of the patients suffer from long-term sequelae and persistent symptoms even 6 months after the initial infection. METHODS: This prospective, observational study included 58 participants, 27 of whom were long COVID patients with persistent symptoms > 12 weeks after recovery from PCR-confirmed SARS-CoV-2 infection. Fifteen healthy volunteers and a historical cohort of critically ill COVID-19 patients (n = 16) served as controls. All participants underwent sublingual videomicroscopy using sidestream dark field imaging. A newly developed version of Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell velocity (VRBC) and the microvascular health score (MVHS™) in sublingual microvessels with diameters 4-25 µm. MEASUREMENTS AND MAIN RESULTS: Although dimensions of the glycocalyx were comparable to those of healthy controls, a µm-precise analysis showed a significant decrease of vascular density, that exclusively affected very small capillaries (D5: - 45.16%; D6: - 35.60%; D7: - 22.79%). Plotting VRBC of capillaries and feed vessels showed that the number of capillaries perfused in long COVID patients was comparable to that of critically ill COVID-19 patients and did not respond adequately to local variations of tissue metabolic demand. MVHS was markedly reduced in the long COVID cohort (healthy 3.87 vs. long COVID 2.72 points; p = 0.002). CONCLUSIONS: Our current data strongly suggest that COVID-19 leaves a persistent capillary rarefication even 18 months after infection. Whether, to what extent, and when the observed damage might be reversible remains unclear.

Sustained Impairment in Cardiopulmonary Exercise Capacity Testing in Patients after COVID-19: A Single Center Experience.

Background: Following COVID-19, patients often present with ongoing symptoms comparable to chronic fatigue and subjective deterioration of exercise capacity (EC), which has been recently described as postacute COVID-19 syndrome. Objective: To objectify the reduced EC after COVID-19 and to evaluate for pathologic limitations. Methods: Thirty patients with subjective limitation of EC performed cardiopulmonary exercise testing (CPET). If objectively limited in EC or deteriorated in oxygen pulse, we offered cardiac stress magnetic resonance imaging (MRI) and a follow-up CPET. Results: Eighteen male and 12 female patients were included. Limited relative EC was detected in 11/30 (36.7%) patients. Limitation correlated with reduced body weight-indexed peak oxygen (O2) uptake (peakV̇O2/kg) (mean 74.7 (±7.1) % vs. 103.6 (±14.9) %, p < 0.001). Reduced peakV̇O2/kg was found in 18/30 (60.0%) patients with limited EC. Patients with reduced EC widely presented an impaired maximum O2 pulse (75.7% (±5.6) vs. 106.8% (±13.9), p < 0.001). Abnormal gas exchange was absent in all limited EC patients. Moreover, no patient showed signs of reduced pulmonary perfusion. Using cardiac MRI, diminished biventricular ejection fraction was ruled out in 16 patients as a possible cause for reduced O2 pulse. Despite noncontrolled training exercises, follow-up CPET did not reveal any exercise improvements. Conclusions: Deterioration of EC was not associated with ventilatory or pulmonary vascular limitation. Exercise limitation was related to both reduced O2 pulse and peakV̇O2/kg, which, however, did not correlate with the initial severity of COVID-19. We hypothesize that impaired microcirculation or limited peripheral O2 utilization might be causative for prolonged deterioration of EC following acute COVID-19 infection.