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
Authors: Mesquida Jaume , Caballer A. , Cortese L. , Vila C. , Karadeniz U. , Pagliazzi M. , Zanoletti M. , Pacheco A. Pérez , Castro P. , García-de-Acilu M. , Mesquita R. C. , Busch D. R. , Durduran T. ,   the HEMOCOVID-19 Consortium, Durduran Turgut , Pagliazzi Marco , Cortese Lorenzo , Zanoletti Marta , Karadeniz Umut , Mesquida Jaume , Caballer Alba , Nogales Sara , Espinal Cristina , Gruartmoner Guillem , Terán Puri Pérez , Vilà Clara , Picazo Lucía , Ferrer Ricard , De Acilu Marina García , Chiscano Luis , Mera Abraham , Castro Pedro , Téllez Adrián , Fernández Sara , Matas Ana , Fuentes Fernando , Serra Isabel , Romero David , Font Francesc , Myers Tim , Busch David R. , Dave Siddharth , Cheruku Sreekanth , Choi Christopher , Lahsaei Peiman , Olson DaiWai , Pacheco Argelia Pérez , Quispe Siccha Rosa María , Liceaga Eduardo , De Oca Hernández Félix Jerandy Monte , Besen Bruno Adler Maccagnan Pinheiro , Taniguchi Leandro Utino , Mendes Pedro Vitale , Mesquita Rickson Coelho , Soto Andrés Fabián Quiroga , Aventurato Italo Karmann , de Oliveira Laís Bacchin , Delazari Lilian Elisabete Bernardes , dos Santos Lígia , Ratti Roceto , Falcão Antonio Luis Eiras , Marin-Corral Judith , Serrano-Loyola Raúl , Carbajal-Robles Verónica , Santillan-Aguayo Enrique , Parada-Guzmán Melvin , Menezes-Forti Rodrigo , Bacchin Luis , Lívio-Emidio Gabriela 
Published: November 2021

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.