The future of intensive care: the study of the microcirculation will help to guide our therapies.

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

Coronary microcirculatory dysfunction in hypercholesterolemic patients with COVID-19: potential benefit from cholesterol-lowering treatment.

Patients with hypercholesterolemia often have coronary microvascular dysfunction (CMD). Viral infections, such as the SARS-CoV-2 infection, may also result in CMD. Three non-randomized studies have shown significant beneficial effects of statins on CMD in non-infected patients. Similarly, in SARS-CoV-2 - infected patients one beneficial mechanism of action of statins may be the amelioration of endothelial dysfunction, which is a major driver of CMD. Apart from statins, lipoprotein apheresis and PCSK9 inhibitors can also improve or even reverse CMD. The potential reversal of CMD by using effective cholesterol-lowering medications during and after COVID-19 infection, especially in hypercholesterolemic COVID-19 patients, is important.KEY MESSAGESCoronary microvascular dysfunction (CMD) is common in patients hospitalized with SARS-CoV-2 infectionThree nonrandomized studies in non-infected patients are showing the beneficial effects of statin treatment on CMDEffective cholesterol-lowering medication during and after SARS-CoV-2 infection, especially in hypercholesterolemic COVID-19 patients, is of great significance.

Post-COVID-More than chronic fatigue?

After the first COVID-19 survivors were medically treated in Germany from spring 2020 onwards, various courses of the disease emerged that, in addition to the acute infection, led to prolonged symptoms (long COVID), but also to a symptomatic course beyond 12 weeks, which is referred to as "post-COVID syndrome" (PCS). Currently, the incidence of PCS is estimated to be approximately 15% of all symptomatically infected patients, although over- or underestimations may occur due to the soft definition and lack of control groups. The etiology of PCS is currently unknown. The following pathogenetic processes are discussed in particular: an endothelial dysfunction with microcirculatory disturbances and subsequent organ damage, a residual virus or virus particles, and/or an excessive autoimmune process. Due to the large number of organs that may be affected, PCS presents as a very complex clinical picture with up to 200 described symptoms. An evidence-based causal therapy for PCS has not yet been established. The guideline-based inpatient rehabilitation measures adapted to the individual patient resources have proven to be an effective therapy and should therefore be involved in the therapeutic concept at an early stage. Post-COVID syndrome is a multicomplex disease that can have a considerable impact on the quality of life, but also on the professional performance of the affected patients. Thus, it is clearly more than just a chronic fatigue syndrome. In the interest of our patients, treating physicians should take this disease seriously, clarify the differential diagnoses, and provide sensitive therapeutic care.

NEUROPROTECTIVE AND ANTIOXIDANT POTENTIAL OF MONTELUKAST-ACETYLCYSTEINE COMBINATION THERAPY FOR BRAIN PROTECTION IN PATIENTS WITH COVID-19 INDUCED PNEUMONIA.

Direct critical attack of the coronavirus on the alveoli and the excessive release of a large number of cytokines (IL-6, IL-1, TNF-α, etc.) provides suitable conditions for the further development of acute respiratory distress syndrome (ARDS) and severe acute respiratory failure. Serious decrease in blood oxygenation often lead to the deterioration of macro- and microcirculation, irreversible brain damage and hence, persistent neurological and mental disorders despite background intensive therapy and adequate respiratory support. Therefore, the aim of our open prospective observational study was to investigate the neuroprotective and antioxidant effectiveness of montelukast-acetylcysteine combination therapy for brain protection in patients with COVID-19 viral pneumonia. A study was performed for five hundred seventy-eight (n=578) outpatients who were tested positive for novel coronavirus (SARS-CoV-2) by nasopharyngeal swap. The median age of patients was 62±17.45 years. In addition to clinical features and RT-PCR results, chest CT and chest X-ray (CXR) with high sensitivity were also very helpful for the early identification of viral pneumonia and COVID-19 disease assessment. Considering the severity of Covid-19 pneumonia and the level of arterial oxygen saturation (transcutaneous hemoglobin oxygen saturation) on room air, all patients were divided into three major groups. Group 1 (n=288) consisted of patients with a mild shift in oxygen saturation (SpO2 ≥ 95%) and well-defined pulmonary lesions (within 1-2 segments) without concomitant diseases; the second group (Group 2, n=250) included patients with clinical manifestations of moderate severity associated with a current saturation of 90-95% (SpO2) and small pulmonary lesions on chest X-ray in the presence of concomitant diseases: arterial hypertension (stage III) or CHF (FC/NYHA-2), coronary heart disease or type 2 diabetes, cancer, tuberculosis, etc. Most of the patients in third group (Group 3, n=48), during imaging studies, showed bilateral lung affection with low and peripheral distribution (with both - either ground glass opacities or multiple pulmonary nodules) and cardiomegaly. The respiratory failure of stage II-III (current oxygen saturation SpO2 75-90%), high respiratory rate (≥25 per minute), hemodynamic impairment (BP≤100/60 mm Hg. Art., heart rate ≥125/min) were the most common objective clinical findings seen in this subset of patients. Laboratory changes included leukopenia less than 4.0x109/L or leukocytosis (≥10.0X109/L). Background respiratory support with low-flow oxygen therapy and combined pharmacotherapy, where, along with montelukast and acetylcysteine, patients were prescribed a cephalosporin, a fluoroquinolone, an antifungal drug, a histamine blocker, an antiplatelet agent, a complex of B vitamins, led to a significant improvement in symptoms and laboratory parameters during the course of the disease. The mean values of the blood biomarkers (CRP - 21.46±4.43 mg/l, LDH - 410.71±40.63 U/l, procalcitonin - 1.08±0.31 ng/ml, and ferritin - 270.43±27.23 ng/ml) return to normal by the 20th day after the fever subsides. Laboratory parameters before and after treatment course showed statistically significant differences between variables (p<0.05). No patient in Group 3 received JAK inhibitors (tofacitinib and baricitinib), IL-6 (olokizumab), IL-17A (netakimab) and glucocorticosteroids, however, recovery rates were completely good. Assessment of the patient's neurological status (based on the NIHSS scores) revealed no signs of neurological changes. Thus, based on the data given, it can be concluded that the high efficacy of the acetylcysteine/montelukast combination (as neuroprotectors) in pneumonia caused by COVID-19 is due to the effect of drugs on key mechanisms of pathogenesis: reduction of oxidative stress as drugs (combination) ensuring the free radical scavenging; stimulation of glutathione synthesis; suppression of cytokine storm; reduction of bronchospasm, mucus secretion and airway edema; lowering of BBB permeability and the ability to improve cerebral microcirculatory perfusion in the presence of antiplatelet agents. In conclusion, the combination of montelukast and acetylcysteine may provide an effective, safe, multicomponent approach to the prevention of hypoxic brain injury in patients with COVID-19 pneumonia.

Epidemiology, Pathophysiology, Diagnosis, and Principles of Management of Takotsubo Cardiomyopathy: A Review.

Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is a reversible syndrome commonly found among patients presenting for acute coronary syndromes, especially women. With the COVID-19 pandemic, the incidence of takotsubo cardiomyopathy was dramatically increased. However, this clinical cardiac entity remains underdiagnosed, largely due to the interplay with acute coronary syndrome. The pathophysiology of takotsubo cardiomyopathy is miscellaneous, including coronary vasospasm, microcirculatory dysfunction, catecholamine surge, and sympathetic overdrive. Diagnosing takotsubo cardiomyopathy requires a high index of clinical suspicion and multimodality tests. To date, there are no guidelines for the management of takotsubo cardiomyopathy. Thus, available data are derived from case series, retrospective analyses, and experts' opinions. Heart failure medicines were investigated in takotsubo cardiomyopathy patients. Evidence supports the benefits of angiotensin-converting enzyme inhibitors and angiotensin receptors blockers use on mortality and recurrence rates, while results from use of beta-blockers are controversial. In complicated cases, inotropes are preferred over vasopressors, except in the presence of left ventricular outflow tract obstruction, in which medical therapy is limited to fluids administration and beta-blockers. Use of oral vitamin K antagonist can benefit patients at high thrombo-embolic risk for up to 3 months. Mechanical supports are reserved for refractory hemodynamically unstable cases. This review aims to provide an update on the epidemiology, diagnosis, and outcomes of takotsubo cardiomyopathy, and an extended discussion on the management of complicated and non-complicated cases.

The impact of platelets on pulmonary microcirculation throughout COVID-19 and its persistent activating factors.

Patients with COVID-19 often have hypoxemia, impaired lung function, and abnormal imaging manifestations in acute and convalescent stages. Alveolar inflammation, pulmonary vasculitis, and thromboembolism synergistically damage the blood-air barrier, resulting in increased pulmonary permeability and gas exchange disorders. The incidence of low platelet counts correlates with disease severity. Platelets are also involved in the impairment of pulmonary microcirculation leading to abnormal lung function at different phases of COVID-19. Activated platelets lose the ability to protect the integrity of blood vessel walls, increasing the permeability of pulmonary microvasculature. High levels of platelet activation markers are observed in both mild and severe cases, short and long term. Therefore, the risk of thrombotic events may always be present. Vascular endothelial injury, immune cells, inflammatory mediators, and hypoxia participate in the high reactivity and aggregation of platelets in various ways. Microvesicles, phosphatidylserine (PS), platelets, and coagulation factors are closely related. The release of various cell-derived microvesicles can be detected in COVID-19 patients. In addition to providing a phospholipid surface for the synthesis of intrinsic factor Xase complex and prothrombinase complex, exposed PS also promotes the decryption of tissue factor (TF) which then promotes coagulant activity by complexing with factor VIIa to activate factor X. The treatment of COVID-19 hypercoagulability and thrombosis still focuses on early intervention. Antiplatelet therapy plays a role in relieving the disease, inhibiting the formation of the hypercoagulable state, reducing thrombotic events and mortality, and improving sequelae. PS can be another potential target for the inhibition of hypercoagulable states.

Hyperviscosity syndromes; hemorheology for physicians and the use of microfluidic devices.

PURPOSE OF REVIEW: Hyperviscosity syndromes can lead to significant morbidity and mortality. Existing methods to measure microcirculatory rheology are not readily available and limited in relevance and accuracy at this level. In this review, we review selected hyperviscosity syndromes and the advancement of their knowledge using microfluidic platforms. RECENT FINDINGS: Viscosity changes drastically at the microvascular level as the physical properties of the cells themselves become the major determinants of resistance to blood flow. Current, outdated viscosity measurements only quantify whole blood or serum. Changes in blood composition, cell number, or the physical properties themselves lead to increased blood viscosity. Given the significant morbidity and mortality from hyperviscosity syndromes, new biophysical tools are needed and being developed to study microvascular biophysical and hemodynamic conditions at this microvascular level to help predict those at risk and guide therapeutic treatment. SUMMARY: The use of 'lab-on-a-chip' technology continues to rise to relevance with point of care, personalized testing and medicine as customizable microfluidic platforms enable independent control of many in vivo factors and are a powerful tool to study microcirculatory hemorheology.

Microvascular Thrombosis as a Critical Factor in Severe COVID-19.

Platelet-endothelial interactions have a critical role in microcirculatory function, which maintains tissue homeostasis. The subtle equilibrium between platelets and the vessel wall is disturbed by the coronavirus disease 2019 (COVID-19), which affects all three components of Virchow's triad (endothelial injury, stasis and a hypercoagulable state). Endotheliitis, vasculitis, glycocalyx degradation, alterations in blood flow and viscosity, neutrophil extracellular trap formation and microparticle shedding are only few pathomechanisms contributing to endothelial damage and microthrombosis resulting in capillary plugging and tissue ischemia. In the following opinion paper, we discuss major pathological processes leading to microvascular endothelial activation and thrombosis formation as a possible major adverse factor driving the deterioration of patient disease course in severe COVID-19.

New developments in translational microcirculatory research.

Microvascular disease plays a critical role in systemic end-organ dysfunction, and treatment of microvascular pathologies may greatly reduce cardiovascular morbidity and mortality. The Call for Papers collection: New Developments in Translational Microcirculatory Research highlights key advances in our understanding of the role of microvessels in the development of chronic diseases as well as therapeutic strategies to enhance microvascular function. This Mini Review provides a concise summary of these advances and draws from other relevant research to provide the most up-to-date information on the influence of cutaneous, cerebrovascular, coronary, and peripheral microcirculation on the pathophysiology of obesity, hypertension, cardiovascular aging, peripheral artery disease, and cognitive impairment. In addition to these disease- and location-dependent research articles, this Call for Papers includes state-of-the-art reviews on coronary endothelial function and assessment of microvascular health in different organ systems, with an additional focus on establishing rigor and new advances in clinical trial design. These articles, combined with original research evaluating cellular, exosomal, pharmaceutical, exercise, heat, and dietary interventional therapies, establish the groundwork for translating microcirculatory research from bench to bedside. Although numerous studies in this collection are focused on human microcirculation, most used robust preclinical models to probe mechanisms of pathophysiology and interventional benefits. Future work focused on translating these findings to humans are necessary for finding clinical strategies to prevent and treat microvascular dysfunction.

Selective CB2 Receptor Agonist, HU-308, Reduces Systemic Inflammation in Endotoxin Model of Pneumonia-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB2) has been shown to reduce cytokine release in various in vivo and in vitro studies. Herein, we investigated the effect of HU-308, a specific CB2 agonist, on systemic and pulmonary inflammation in a model of pneumonia-induced ALI. C57Bl/6 mice received intranasal endotoxin or saline, followed by intravenous HU-308, dexamethasone, or vehicle. ALI was scored by histology and plasma levels of select inflammatory mediators were assessed by Luminex assay. Intravital microscopy (IVM) was performed to assess leukocyte adhesion and capillary perfusion in intestinal and pulmonary microcirculation. HU-308 and dexamethasone attenuated LPS-induced cytokine release and intestinal microcirculatory impairment. HU-308 modestly reduced ALI score, while dexamethasone abolished it. These results suggest administration of HU-308 can reduce systemic inflammation without suppressing pulmonary immune response in pneumonia-induced ALI and systemic inflammation.

Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect?

Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue, cognitive dysfunction, muscle weakness and orthostatic intolerance (OI). These symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS). OI is highly prevalent in ME/CFS and develops early during or after acute COVID-19 infection. The causes for OI are unknown and autonomic dysfunction is hypothetically assumed to be the primary cause, presumably as a consequence of neuroinflammation. Here, we propose an alternative, primary vascular mechanism as the underlying cause of OI in Long COVID. We assume that the capacitance vessel system, which plays a key role in physiologic orthostatic regulation, becomes dysfunctional due to a disturbance of the microvessels and the vasa vasorum, which supply large parts of the wall of those large vessels. We assume that the known microcirculatory disturbance found after COVID-19 infection, resulting from endothelial dysfunction, microthrombus formation and rheological disturbances of blood cells (altered deformability), also affects the vasa vasorum to impair the function of the capacitance vessels. In an attempt to compensate for the vascular deficit, sympathetic activity overshoots to further worsen OI, resulting in a vicious circle that maintains OI. The resulting orthostatic stress, in turn, plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.

Post-COVID-19 Syndrome: Retinal Microcirculation as a Potential Marker for Chronic Fatigue.

Post-COVID-19 syndrome (PCS) is characterized by persisting sequelae after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). PCS can affect patients with all COVID-19 disease severities. As previous studies have revealed impaired blood flow as a provoking factor triggering PCS, it was the aim of the present study to investigate the potential association between self-reported chronic fatigue and retinal microcirculation in patients with PCS, potentially indicating an objective biomarker. A prospective study was performed, including 201 subjects: 173 patients with PCS and 28 controls. Retinal microcirculation was visualized by OCT angiography (OCT-A) and quantified using the Erlangen-Angio-Tool as macula and peripapillary vessel density (VD). Chronic fatigue (CF) was assessed according to the variables of Bell's score, age and gender. VDs in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) were analyzed, considering the repetitions (12 times). Seropositivity for autoantibodies targeting G protein-coupled receptors (GPCR-AAbs) was determined by an established cardiomyocyte bioassay. Taking account of the repetitions, a mixed model was performed to detect possible differences in the least square means between the different groups included in the analysis. An age effect in relation to VD was observed between patients and controls (p < 0.0001). Gender analysis showed that women with PCS showed lower VD levels in the SVP compared to male patients (p = 0.0015). The PCS patients showed significantly lower VDs in the ICP as compared to the controls (p = 0.0001 (CI: 0.32; 1)). Moreover, considering PCS patients, the mixed model revealed a significant difference between those with chronic fatigue (CF) and those without CF with respect to VDs in the SVP (p = 0.0033 (CI: -4.5; -0.92)). The model included variables of age, gender and Bell's score, representing a subjective marker for CF. Consequently, retinal microcirculation might serve as an objective biomarker in subjectively reported chronic fatigue in patients with PCS.

Microcirculatory alterations in critically ill COVID-19 patients analyzed using artificial intelligence.

BACKGROUND: The sublingual microcirculation presumably exhibits disease-specific changes in function and morphology. Algorithm-based quantification of functional microcirculatory hemodynamic variables in handheld vital microscopy (HVM) has recently allowed identification of hemodynamic alterations in the microcirculation associated with COVID-19. In the present study we hypothesized that supervised deep machine learning could be used to identify previously unknown microcirculatory alterations, and combination with algorithmically quantified functional variables increases the model's performance to differentiate critically ill COVID-19 patients from healthy volunteers. METHODS: Four international, multi-central cohorts of critically ill COVID-19 patients and healthy volunteers (n = 59/n = 40) were used for neuronal network training and internal validation, alongside quantification of functional microcirculatory hemodynamic variables. Independent verification of the models was performed in a second cohort (n = 25/n = 33). RESULTS: Six thousand ninety-two image sequences in 157 individuals were included. Bootstrapped internal validation yielded AUROC(CI) for detection of COVID-19 status of 0.75 (0.69-0.79), 0.74 (0.69-0.79) and 0.84 (0.80-0.89) for the algorithm-based, deep learning-based and combined models. Individual model performance in external validation was 0.73 (0.71-0.76) and 0.61 (0.58-0.63). Combined neuronal network and algorithm-based identification yielded the highest externally validated AUROC of 0.75 (0.73-0.78) (P < 0.0001 versus internal validation and individual models). CONCLUSIONS: We successfully trained a deep learning-based model to differentiate critically ill COVID-19 patients from heathy volunteers in sublingual HVM image sequences. Internally validated, deep learning was superior to the algorithmic approach. However, combining the deep learning method with an algorithm-based approach to quantify the functional state of the microcirculation markedly increased the sensitivity and specificity as compared to either approach alone, and enabled successful external validation of the identification of the presence of microcirculatory alterations associated with COVID-19 status.

Acute Limb Ischemia due to Arterial Thrombosis in a Patient with COVID-19 Pneumonia: A Case Report.

The COVID-19 pandemic has caused more than 4 million deaths worldwide to date. During the course of the COVID-19 pandemic, thrombotic complications due to hypercoagulable state have emerged as an important issue. Acute limb ischemia is one of emergency cases in vascular disease caused by a sudden decrease in arterial limbs perfusion. Here, we report a 53-year-old male patient with severe COVID-19 and a history of uncontrolled type 2 diabetes mellitus (T2DM) who developed extensive arterial thrombosis and limb ischemia despite being on therapeutic-dose anticoagulation, requiring surgical intervention. Right and left leg open thrombectomy was performed at day 7 after admission due to the excruciating pain and the worsening of the limb conditions. The patient was transferred to intensive care unit in emergency room because of the unstable hemodynamic and passed away a few hours after the surgery. For critically ill patients with COVID-19, special attention should be paid to abnormal coagulation dysfunction and microcirculatory disorders.

Chronic Fatigue Associated with Post-COVID Syndrome versus Transient Fatigue Caused by High-Intensity Exercise: Are They Comparable in Terms of Vascular Effects?

Purpose: The pathophysiology of chronic fatigue associated with post-COVID syndrome is not well recognized. It is assumed that this condition is partly due to vascular dysfunction developed during an acute phase of infection. There is great demand for a diagnostic tool that is able to clinically assess post-COVID syndrome and monitor the rehabilitation process. Patients and Methods: The Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for the analysis of basal microcirculatory oscillations and reactive hyperemia induced by transient ischemia. The FMSF was used to measure vascular circulation in 45 patients with post-COVID syndrome. The results were compared with those for a group of 26 amateur runners before and after high-intensity exercise as well as for a control group of 32 healthy age-matched individuals. Results: Based on the observed changes in the NOI (Normoxia Oscillatory Index) and RHR (Reactive Hyperemia Response) parameters measured with the FMSF technique, it was found that chronic fatigue associated with post-COVID syndrome is comparable with transient fatigue caused by high-intensity exercise in terms of vascular effects, which are associated with vascular stress in the macrocirculation and microcirculation. Acute and chronic fatigue symptomatology shared similarly altered changes in the NOI and RHR parameters and both can be linked to calcium homeostasis modification. Conclusion: The NOI and RHR parameters measured with the FMSF technique can be used for non-invasive clinical assessment of post-COVID syndrome as well as for monitoring the rehabilitation process.

COVID-19 and Therapeutic Apheresis.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is an unprecedented challenge for the global community. The pathogenesis of COVID-19, its complications and long term sequelae (so called Long/Post-COVID) include, in addition to the direct virus-induced tissues injury, multiple secondary processes, such as autoimmune response, impairment of microcirculation, and hyperinflammation. Similar pathological processes, but in the settings of neurological, cardiovascular, rheumatological, nephrological, and dermatological diseases can be successfully treated by powerful methods of Therapeutic Apheresis (TA). We describe here the rationale and the initial attempts of TA treatment in severe cases of acute COVID-19. We next review the evidence for the role of autoimmunity, microcirculatory changes and inflammation in pathogenesis of Long/Post COVID and the rationale for targeting those pathogenic processes by different methods of TA. Finally, we discuss the impact of COVID-19 pandemic on patients, who undergo regular TA treatments due to their underlying chronic conditions, with the specific focus on the patients with inherited lipid diseases being treated at the Dresden University Apheresis Center.

[Severe pseudomembranous colitis in patients with previous coronavirus infection]. / Psevdomembranoznyi kolit na fone perenesennoi koronavirusnoi infektsii.

OBJECTIVE: To analyze treatment outcomes in patients with severe pseudomembranous colitis and previous coronavirus infection. MATERIAL AND METHODS: We retrospectively analyzed treatment outcomes, clinical, laboratory and histological data in convalescents of COVID-19 who admitted to the department of coloproctology for moderate-to-severe pseudomembranous colitis confirmed by endoscopic examination between 2020 and 2021. RESULTS: There were 13 patients with moderate pseudomembranous colitis and 6 ones with severe pseudomembranous colitis. Mean period after recovery from coronavirus infection was 19 days. Endoscopy revealed whitish-yellow or gray raised plaques on colonic mucosa in all cases. Four patients with signs of peritonitis underwent emergency surgery. Three patients had perforation of caecum; one patient had perforation of sigmoid colon and widespread peritonitis. Two patients underwent urgent surgery for progressive toxic megacolon and ineffective therapy. Subtotal colectomy and ileostomy were performed in all cases. Histological examination revealed necrosis of not only superficial layer of colon mucosa typical for clostridial colitis, but also the entire thickness of mucosa, as well as submucosal and partially muscular layers in some cases. Mucosal crypt atrophy, fibrinoid effusion in muscular layer, diffuse polymorphonuclear cell infiltration and necrosis of muscular and submucosal nerve plexuses, as well as necrosis of vascular walls with deposition of hyaline-like structures characterize microcirculatory ischemic processes in the colon wall. CONCLUSION: Severe pseudomembranous colitis associated with COVID-19 may not be associated with clostridial infection. Further analysis of possible ischemic etiology and pathogenesis of gastrointestinal lesions in COVID-19 is needed for preventive and therapeutic measures.