DETECTION AND QUANTIFICATION OF MICROCIRCULATORY DYSFUNCTION IN SEVERE COVID-19 NOT REQUIRING MECHANICAL VENTILATION: A THREE-ARM COHORT STUDY.

Abstract: Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non-COVID-19 intensive care unit (ICU)-matched controls. A validation cohort included healthy, comorbidity-free patients. The primary outcome compared tissue oxygen resaturation slope (rStO 2 ) in COVID-19 patients and non-COVID ICU controls. rStO 2 was measured post a 3-min vaso-occlusive test during post-occlusive reactive hyperemia (PORH). Additionally, microvascular reactivity was assessed using perfusion index (PI) during PORH and laser speckle contrast imaging post iontophoresis with acetylcholine (ACH), sodium nitroprusside (SNP), and sublingual microcirculation. Results: Overall, 75 patients (25 per cohort) were included. COVID-19 patients exhibited greater severity than ICU controls, as indicated by their SOFA scores (4.0 [3.0; 4.0] vs. 1.0 [0; 1.0], P < 0.001) and PaO 2 /FiO 2 ratios (113 [82; 150] vs. 443 [348; 533], P < 0.001). No significant difference was observed in rStO 2 between the groups. COVID-19 patients showed longer time in reaching peak PI ( P = 0.025), reduced vasodilation with ACH and SNP ( P = 0.010 and P = 0.018, respectively), and increased microvascular density ( P = 0.019) compared to non-COVID-19 ICU controls. Conclusion: We observed evidence of MD in COVID-19 patients through various microcirculatory parameters. This study's reproducible multimodal approach facilitates acute MD detection across multiple clinical applications. Limitations included the observational design, limited statistical power, single-time microvascular measurements, varying illness severity among groups, and possible influences of treatments and vaccinations on MD. Trial registration : Clinical-Trials.gov (NCT04773899).