Leukocyte-platelet aggregates in the pathogenesis of respiratory failure in patients with COVID-19 with varying degrees of oxygen support

Introduction. Thrombo-inflammatory changes in the alveolar-capillary membrane are significant links in the pathogenesis of respiratory failure in COVID-19. This study investigates whether leukocyte-platelet aggregates contribute to its development and, if so, the mechanisms involved.

Aim. To examine the quantitative changes in leukocyteplatelet aggregates in patients with COVID-19 receiving different levels of oxygen support.

Materials and methods. The study included 134 COVID-19 patients of varying severity and 20 volunteers examined in the pre-pandemic period. The criterion for dividing the studied patients into groups was the ratio of blood oxygen saturation to its inhaled fraction, investigated by pulse oximetry. Three groups were formed depending on the value of the index: in the first (n=48), the SpO2/FiO2 index was above 450%, in the second (n=55) it ranged from 370 to 449%, and in the third (n=51) the index was up to 369%. The enumeration of blood cells, major leukocyte populations, lymphocyte subpopulations, and plateletleukocyte complexes was performed using the CytoFLEX LX flow cytometer (Beckman Coulter, USA).

Results. In the third group, there was a decrease in the number of monocytic aggregates (p<0.001) and their subfractions, as well as the number of lymphocyte rosettes (p=0.015), while the number of lymphocytes (p<0.001) and neutrophil interactions (p=0.05) increased in parallel. In the second group, there was a statistically significant decrease in the total number of monocytic aggregates (p=0.038), and in the third, the number of aggregates with classical monocytes (p=0.012).

Conclusion. The number of lymphocyte-platelet and monocyte-platelet aggregates decreased in patients with different types of oxygen support, while neutrophil-platelet aggregates increased and correlated with the SpO2/FiO2 ratio.

1. Israilova V.K., Mirsaliyev M.M., Aytkozhin G.K., Yermekbay A.A. [Respiratory support for pneumonia patients in the COVID-19 pandemic (review article)]. Vestnik Kazahskogo nacional'nogo medicinskogo universiteta = Vestnik KazNMU 2020; 4:40–44 (in Russian).

2. Makatsariya A.D., Slukhanchuk E.V., Bitsadze V.O., Khizroeva J.Kh., Tretyakova M.V., Shkoda A.S., Akinshina S.V., Makatsariya N.A., Tsibizova V.I., Gris J., Elalamy I., Ay С., Grandone E. [Thrombotic storm, hemostasis disorders and thromboinflammation in COVID-19]. Akusherstvo, ginekologiya i reproduktsiya = Obstetrics Gynecology and Reproduction. 2021; 15(5):499–514 (in Russian). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2021.247

3. Aleksandrova N.P. [Pathogenesis of respiratory failure in coronavirus disease (COVID-19)]. Integrativnaya fiziologiya = Integrative Physiology 2020; 1(4):285–293 (in Russian). https://doi.org/10.33910/2687-1270-2020-1-4-285-293

4. Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolyan A.A. [Standardized technology «Research subpopulation composition of peripheral blood lymphocytes using flow cytometry analyzers»]. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology 2014; 8(17-4):974–992 (in Russian).

5. Catoire P., Tellier E., de la Rivière C., Beauvieux M.C., Valdenaire G., Galinski M., Revel P., Combes X., Gil-Jardiné C. Assessment of the SpO2/FiO2 ratio as a tool for hypoxemia screening in the emergency department. Am. J. Emerg. Med. 2021; 44:116–120. https://doi.org/10.1016/j.ajem.2021.01.092

6. Syed F., Li W., Relich R.F., Russell P.M., Zhang S., Zimmerman M.K., Yu Q. Excessive matrix metalloproteinase1 and hyperactivation of endothelial cells occurred in COVID-19 patients and were associated with the severity of COVID19. J. Infect. Dis. 2021; 224(1): 60–69. https://doi.org/10.1093/infdis/jiab167

7. Bulanova E.L., Rabotinsky S.E., Degtyarev P.A., Sinyavkin D.O., Bulanov A.Yu. [Thrombocytopenia in the ICU before and during the pandemic of the new coronavirus infection COVID-19: a comparative retrospective cohort study]. Vestnik intensivnoy terapii im. A.I. Saltanova = Annals of Critical Care 2022; 4:66–73 (in Russian). https://doi.org/10.21320/1818-474X-2022-4-66-73