Capillary Leukocytes, Microaggregates, and the Response to Hypoxemia in the Microcirculation of Coronavirus Disease 2019 Patients

• Published in: Critical care medicine Vol. 49; no. 4; pp. 661 - 670
• Main Authors: Favaron, Emanuele, Ince, Can, Hilty, Matthias P., Ergin, Bülent, van der Zee, Philip, Uz, Zühre, Wendel Garcia, Pedro D., Hofmaenner, Daniel A., Acevedo, Claudio T., van Boven, Wim Jan, Akin, Sakir, Gommers, Diederik, Endeman, Henrik
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins 01-04-2021
• Subjects: Capillaries; Clinical Investigations; COVID-19 - mortality; Erythrocytes; Female; Humans; Hypoxia - etiology; Leukocytes; Male; Microcirculation - physiology; Middle Aged
• ISSN: 0090-3493; 1530-0293
• DOI: 10.1097/CCM.0000000000004862

In this study, we hypothesized that coronavirus disease 2019 patients exhibit sublingual microcirculatory alterations caused by inflammation, coagulopathy, and hypoxemia.
Multicenter case-controlled study.
Two ICUs in The Netherlands and one in Switzerland.
Thirty-four critically ill coronavirus disease 2019 patients were compared with 33 healthy volunteers.
None.
The microcirculatory parameters quantified included total vessel density (mm × mm-2), functional capillary density (mm × mm-2), proportion of perfused vessels (%), capillary hematocrit (%), the ratio of capillary hematocrit to systemic hematocrit, and capillary RBC velocity (μm × s-1). The number of leukocytes in capillary-postcapillary venule units per 4-second image sequence (4 s-1) and capillary RBC microaggregates (4 s-1) was measured. In comparison with healthy volunteers, the microcirculation of coronavirus disease 2019 patients showed increases in total vessel density (22.8 ± sd 5.1 vs 19.9 ± 3.3; p < 0.0001) and functional capillary density (22.2 ± 4.8 vs 18.8 ± 3.1; p < 0.002), proportion of perfused vessel (97.6 ± 2.1 vs 94.6 ± 6.5; p < 0.01), RBC velocity (362 ± 48 vs 306 ± 53; p < 0.0001), capillary hematocrit (5.3 ± 1.3 vs 4.7 ± 0.8; p < 0.01), and capillary-hematocrit-to-systemic-hematocrit ratio (0.18 ± 0.0 vs 0.11 ± 0.0; p < 0.0001). These effects were present in coronavirus disease 2019 patients with Sequential Organ Failure Assessment scores less than 10 but not in patients with Sequential Organ Failure Assessment scores greater than or equal to 10. The numbers of leukocytes (17.6 ± 6.7 vs 5.2 ± 2.3; p < 0.0001) and RBC microaggregates (0.90 ± 1.12 vs 0.06 ± 0.24; p < 0.0001) was higher in the microcirculation of the coronavirus disease 2019 patients. Receiver-operating-characteristics analysis of the microcirculatory parameters identified the number of microcirculatory leukocytes and the capillary-hematocrit-to-systemic-hematocrit ratio as the most sensitive parameters distinguishing coronavirus disease 2019 patients from healthy volunteers.
The response of the microcirculation to coronavirus disease 2019-induced hypoxemia seems to be to increase its oxygen-extraction capacity by increasing RBC availability. Inflammation and hypercoagulation are apparent in the microcirculation by increased numbers of leukocytes and RBC microaggregates.