Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units

Abstract

Background COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients. Methods This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio). Results Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies. Conclusion Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477. Retrospectively registered 30 December 2020.

Combining L-Arginine with vitamin C improves long-COVID symptoms: The LINCOLN Survey

“…While initial studies on COVID-19 primarily focused on the pulmonary manifestations of the disease 19 , 20 , 21 , 22 , 23 , 24 , other organs including heart, brain, kidney, and the pancreas, were shown to be affected by COVID-19 25 , 26 , 27 . In the Spring of 2020, we were among the first groups to indicate a link between COVID-19 and endothelial dysfunction 28 , 29 , and our view has been later confirmed by other investigators, associating the systemic manifestations of the disease to a direct or indirect involvement of the endothelium 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 . Indeed, endothelial cells express all co-factors necessary for the internalization of SARS-CoV-2 in host cells, including angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), cathepsins B and D, neuropilin-1, transferrin receptor, and others, thereby representing a natural target of SARS-CoV-2 28 , 39 , 40 , 41 , 42 , 43 , 44 , 45 .…”

Exosomal miR-145 and miR-885 Regulate Thrombosis in COVID-19

“…We found that COVID-19 serum (collected on hospital admission) induces endothelial damage including cell apoptosis and alterations of a specialized endothelial feature like angiogenic capacity. This is in line with numerous reports from we and others supporting endothelial involvement in COVID-19 clinical manifestations (Gu et al, 2020;Libby and Luscher, 2020;Perea Polak et al, 2020;Teuwen et al, 2020;Fiorentino et al, 2021;Mesquida et al, 2021;Mone et al, 2021;Qin et al, 2021;Schmaier et al, 2021;Yin et al, 2021;Kelliher et al, 2022;Mone et al, 2022;Otifi and Adiga, 2022;Robles et al, 2022).…”

Association of vasopressors with mortality in critically ill patients with COVID-19: A systematic review and meta-analysis

“…However, microcirculatory flow decreases proportionally to the increasing inflammation, hypercoagulation, and thrombosis, resulting in multi-organ failure at later stages [65,68-70]. In the study by Mesquida et al, patients showed alterations in systemic microcirculatory status, and the degree of these alterations correlated with the severity of the respiratory disease [24]. The relationship between MAP and organ blood flow may be different in critically ill patients with COVID-19 and improving only macrocirculation might be inadequate to maintain tissue perfusion.…”

“…The studies originated from multiple countries, with 13 of coming from institutions located in the USA [20,21,23,[32][33][34][35]38,42,43,45,48,51]. Nineteen studies included only patients admitted in the ICU [20,22,24,25,27,[30][31][32][35][36][37][38][39][43][44][45][46][47]52], five studies included patients admitted in a COVID-19-dedicated HDU [28,29,33,34,42], eight studies included patients who were admitted in both HDU and ICU [21,23,26,40,41,48,49,51], and one study included Emergency Department patients who were later admitted either in the HDU of ICU [50]. Thirty studies included data about patients who received vs. patients who did not receive vasopressors…”