Microcirculation disorders caused by thrombosis are the most important factor determining the pathogenesis of organ damage in severe COVID-19 including the absence of obvious macrohemodynamic instability. However, there are very few publications demonstrating the results of intravital visualization of changes in the microcirculation system in this disease.The objective: to assess the state of microcirculation in patients with viral pneumonia associated with COVID-19 using nail bed microscopy.Subjects and methods. Eleven patients with COVID-19 were examined; they were admitted to the intensive care unit due to progressing acute respiratory failure. Vital microscopy of the microcirculatory bloodstream in the fingers’ nail bed was performed by admission and over time. When assessing microcirculation, the presence of aggregates in the lumen of capillaries and avascular zones, and the linear velocity of blood flow were taken into account. The results were summarized taking with the outcome consideration (6 people recovered, 5 died). Results. Microcirculation disorders were objectively confirmed in all patients. In 100% of cases, microaggregates were detected in the capillary lumen. The values of the mean linear velocity of capillary blood flow turned out to be extremely variable. However, the values of the maximum linear velocities of capillary blood flow in the patients who subsequently died were significantly lower versus survivors (190 μm/sec (135.5; 237) and 387 μm/sec (329.3; 407.5), p = 0.018). The irregularity of blood flow in the visualized field was revealed: when the value of the maximum linear velocity in some capillaries was less than 180 µm/sec, in others, disturbances in the form of pendulum-like movement were already noted. Further slowing down of the blood flow velocity led to the development of stasis and the formation of avascular zones.Conclusion. Impaired microcirculation (decreased blood flow rate in the capillaries, the presence of microaggregates and a lower number of perfused capillaries in the form of avascular zones) develops in all patients with severe COVID-19.

Impaired microcirculation due  to endothelial dysfunction in COVID-19  is considered  to be  the most important link in the pathogenesis of this disease. However, due  to  the  complexity of its  instrumental  assessment  in critically ill patients,  the data available  in  the  literature on specific manifestations of endothelial dysfunction are very contradictory.The objective:  to determine  the most characteristic capillaroscopic signs of microvascular disorders and  to assess  the  state of microcirculation regulation in patients with severe COVID-19.Subjects  and Methods. When admitted  to  the  intensive  care unit,  60 patients with  COVID-19  and  12  patients with chronic cardiovascular pathology without COVID-19 (Comparison Group) were examined. All patients underwent microscopy of the microcirculatory bed of finger nail bed; the following parameters were assessed: diameters of the venous, arterial and transitional parts of capillaries, height of capillary loops, density of capillaries per  1 mm of the  length of the perivascular zone,  the average  linear velocity of capillary blood  flow (LVCBF), and  thickness of the perivascular zone. The presence of avascular zones,  the number of capillaries in the visualized field with circulating aggregates in the lumen, and the shape of capillaries were taken into account.  In addition, an occlusion test using laser Doppler flowmetry was performed  in 32 patients with COVID-19. The maximum post-occlusive increase in blood flow at the moment of cuff deflation was assessed, as well as changes in the mean value of post-occlusive blood flow relative to the baseline within 3 minutes after cuff deflation.Results.  In 53 (88.3%) patients with COVID-19, abnormalities corresponding to chronic microcirculatory changes in the form of predominance of pathological capillary forms were detected. Microaggregates in the lumen of capillaries and decreased linear velocity of blood flow were revealed in 100% of cases. When comparing groups of patients with different outcomes, statistically significant differences were revealed between the LVCBF parameters (in the survivors -  354.35 ± 44.78 pm/sec, in the deceased - 278.4 ± 26.59 pm/sec), as well as between the values of the perivascular zones thickness  (95.35  ±  15.96 microns versus  159.93 ±  19.90 microns). The results of the post-occlusion  test revealed  a significant difference between the groups in terms of the maximum post-occlusion gain (39.42 ± 3.85 BPU in the group with a favorable outcome, 27.69 ± 3.19 BPU in the group with an unfavorable outcome, 47.23 ±  1.78 BPU in the control group). In both groups, there was no increase in this parameter relative to the initial blood flow. At the same time, in the control group, the average index of post-occlusive blood flow was higher than the initial level.Conclusions. Acute microcirculation disorders with decreased linear velocity of capillary blood flow, circulation of aggregates, increased thickness of the perivascular zone were detected in all patients with severe COVID-19 but especially in those with unfavorable outcomes. Vascular tone regulation disorders were manifested by the absence of reactive hyperemia in response to acute ischemia, as well as a decrease in maximal flow-induced increase. These changes fit into the concept of endothelial dysfunction. Signs of chronic microcirculation disorders in most patients increase the risk of severe COVID-19.

It is believed that microcirculation dysfunction in sepsis primarily caused by damage of the endothelium by infectious agents and pro-inflammatory cytokines. Mechanisms of impaired microcirculation in the severe course of COVID-19 and sepsis likely to be similar. However, there are few reports studied microcirculation disorders in patients with COVID-19, and their results are sometimes contradictory. Objective. To assess the microcirculation of patients with severe Covid-19 and the development of bacterial sepsis using nail bed microscopy and laser Doppler flowmetry. Materials and methods. 16 intensive care unit COVID-19 patients subsequently diagnosed with bacterial sepsis were examined. Patients underwent vital capillaroscopy and an occlusive test using laser Doppler flowmetry. The average rate of capillary blood flow, the size of the perivascular zone, the density of capillaries, the presence of intravascular aggregates, the increase in the amplitude of the maximum post-occlusive blood flow and the average value of postocclusive blood flow relative to the initial one were valuated. Additionally, the level of serum proadrenomedullin was evaluated. Studies were performed on the day of admission and in dynamics. Results. By the capillaroscopy analysis, microcirculation disorders were detected in the form of a decrease in the linear speed of capillary blood flow (<400 μm/s), an extention of the perivascular zone (>100 μm), the circulation of microaggregates; the absence of postocclusive hyperemia was determined by an occlusive test. Secondary bacterial infection led to an even greater aggravation of microcirculation disorders: an increase of the perivascular zone, the progression of intravascular aggregation resulting in microthrombosis with a decrease of the density of the capillary network (according to capillaroscopy), as well as a sharp decrease of amplitude maximal increment of blood flow of post-осclusive circulation at the time of an occlusive sample. We also revealed a trend of negative correlation between the level of serum proadrenomedullin and the maximum increase in blood flow during the occlusive test. Conclusion. The secondary bacterial infection in patients with COVID-19 leads to a significant aggravation of microcirculation disorders with the development of perfusion deficiency and interstitial edema. The increased plasma proadrenomedullin level supports the concept of the significant role of endothelial dysfunction in the pathogenesis of severe COVID-10 and bacterial sepsis.