Background: patients on maintenance hemodialysis (MHD) are at high risk of adverse clinical course of COVID-19. Study objective: analysis and evaluation of heart condition and risk factors of adverse clinical course of COVID-19 in patients on MHD. Materials and methods: 85 patients were included in retrospective observational hospital-based study in Moscow City Hospital 52 from 04.15 to 06.02.2020. The endpoints were results of hospitalization: discharge or lethal outcome. Several demographic, anamnestic, clinical and instrumental indicators were analyzed. Among them: gender, age, general and cardiovascular comorbidity (Charlson index, CCI), the type of vascular dialysis access, the etiology of ESKD, dialysis vintage, body mass index (BMI), cardiovascular events (CVE) in the course of hospital stay (myocardial infarction, MI, pulmonary embolism, PE, and others), ICU admission, mechanical ventilation (MV), the results of echocardiography and lung computed tomography (CT). Odds ratio (OR) was calculated and logistic regression with step-by-step algorithm was applied to assess risk factors of adverse outcomes of COVID-19 in cohort under study. Results: The mean age was 65±13 years (59%, males). Mortality in whole cohort was 43.5% (75%, in ICU patients, and 89% in patient on MV). The concomitant diseases were hypertension (92%), ischemic heart disease (54%), recent MI (19%), chronic heart failure (55%), permanent atrial fibrillation (20%) and diabetes (45%). Mean CCI was 6.6±2.4. Obesity was observed in 33% of cases. No statistical confidence was found in CCI (6.3±2.4 points (survivors) vs 7.0±2.3 points, p>0.05), BMI (26.8±5.3 kg/m2 vs 27.1±5.8 kg/m2, p>0.05). The total number of CVE - 20 (4 vs 16, p=0.019), MI - 10%, PE - 6%. No statistically significant difference was found in LV myocardial mass index - average index 140±33 g/m2 (138±36 g/m2 vs 143±30 g/m2, p>0.05), LA volume index - median 35 (33; 40) ml/m2 - 35 (33; 40) ml/m2 vs 36 (35; 38) ml/m2, p>0.05. In 35% systolic disfunction of right ventricle was observed with no difference between groups. The average index of left ventricle ejection fraction (LVEF) was 53±9% (54±6% vs 50±10%, p=0.019). The median of pulmonary artery systolic pressure - 40 mm Hg (30; 53) (38 (30; 52) mm Hg vs 42 mm (34; 53) Hg, p>0.05). The highest OR was calculated for following parameters: MV (OR=31.95% CI 18-121, p=0.0001), CVE (OR=8.3, 95% CI=2.5-2.8, p=0.0001), CCI ≥6 (OR=4.8, CI=1.6-11.2, p=0.002) and LVEF ≤45% (OR=3-8, 95%, CI=1.3-11,3, p=0.018). Regression logistic analysis demonstrated a strong relationship of lethal outcome with MV (OR=18.0) and CVE (OR=8.5), the moderate relationship with male gender (OR=2.1) and CCI (OR=1.25). Conclusion: the predictors of adverse outcome of COVID-19 in patients on MHD are the need for MV, CVE, CCI ≥6, decline of LVEF ≤45%, male gender.

A brief review of current publications about incidence, outcomes and mechanisms of cardiovascular complications in patients with the new coronaviral disease (COVID-19) is given. The possibility of direct deleterious viral effect on the myocardium, negative consequences of cytokine storm, the role of hypoxemia complicating acute respiratory distress syndrome (ARDS), myocardial infarction 1,2 type (MI 1, 2), hypercoagulation, systolic disfunction of right ventricle due to ARDS, recurrent pulmonary embolism (PE) and cardiotoxic effects of drug therapy is discussed. Three case reports of cardiac injury in patients on maintenance hemodialysis (MHD) with COVID-19 are presented. The first case demonstrated MI 2 type due to ischemic imbalance in a patient with severe ARDS in the absence of obstructive coronary arteries lesion. The second case represented coexistent affection of heart as a result of viral myocarditis and cardiotoxic effect of Azithromycin and Plaquenil co-administration. The viral myocarditis was proven by postmortem histological and immunohistochemical tests. The third case demonstrated the diagnostic quest in a patient with recurrent dyspnea due to sequential severe ARDS, viral hemorrhagic exudative pericarditis with cardiac tamponade and PE progression. Currently three basic phenotypes of cardiac injury are distinguished: permanent elevation of myocardial damage markers, MI 1, 2 Type and viral myo/pericarditis. Of note, the course of COVID-19 in patients on MHD is more complicated in comparison with the general population. The initial vulnerability of these patients is determined not only by severe co-morbidity. Some interconfounding pathophysiological processes same to COVID-19 are critically important for the understanding of the current state of the art. The crucial role of persistent chronic inflammation, coagulopathy, pulmonary hypertension, permanent hemodynamic stress and fluctuation of volemic status should also be taken into consideration. MHD by itself is a powerful risk factor which overburdens the course of COVID-19.

Vasculitis associated with the antineutrophilic cytoplasmic antibodies (ANCA) is an autoimmune systemic severe, often life-threatening, disease characterized by necrotizing inflammation of small vessels. In 75-90% of cases of ANCA-associated vasculitis (AAV), a rapidly progressive pauci-immune necrotizing crescentic glomerulonephritis develops. Despite current treatment with high-dose glucocorticoids and either cyclophosphamide or rituximab, patients have a nine-fold increased mortality risk during the first year of disease compared with healthy subjects. This high mortality is attributed mainly to infections and vasculitis activity. Recent data suggest that the activation of the complement system, and in particular the alternative complement pathway, plays a significant role in the pathogenesis of AAV. It has been suggested that neutrophils primed by infection or pro-inflammatory cytokines release properdin, which activates an alternative complement cascade with cleavage of C5 into C5a and C5b. Anaphylatoxin C5a binds to receptors on the surface of neutrophils, enhancing their priming and activation and thus contributing to the inflammation. The randomized clinical trial showed that the selective C5a-receptor inhibitor avakopan was effective in the treatment of AAV. However, avacopan is currently not available in the everyday clinical practice. On the other hand, reports showing successful usage of monoclonal antibody against C5 eculizumab in severe AAV had been published. Here we present four cases of AAV complicated by COVID-19, for which conventional therapy with cyсlophosphamide could not be applied due to the particularly high risk of serious infectious complications, and eculizumab was used off-label by decision of the medical council and special commission. Taking this decision, we took into account data demonstrating the role of complement activation and, in particular, C5a in the pathogenesis of acute lung disease, induced by pathogenic viruses. Moreover, the successful usage of eculizumab in severe COVID-19 was reported recently. Thus, we sought to apply an approach aimed simultaneously at the pathogenetic mechanisms of both AAV and viral lung damage.

Kidney damage is common in patients with severe forms of COVID-19 and associated with poor prognosis. The causes and nature of kidney damage at COVID-19 have not yet been determined. The study aimed to investigate the incidence, causes and nature of kidney damage in patients with COVID-19. The data obtained from 220 patients, died from COVID-19 between April 20 and May 20, 2020. At the time of hospitalization, 55 (25%) patients had features of chronic kidney disease (CKD). Acute kidney injury (AKI) developed in 135 patients (61%), its frequency did not differ significantly depending on the baseline renal function (67% vs 61% in patients with CKD and with initially normal function, respectively). The only significant predictor of AKI development was the duration of mechanical ventilation (6.1 vs 1.7 days). The number of patients receiving mechanical ventilation or ECMO for 5 or more days was 43% vs 10% for AKI and normal renal function, respectively. Pathologic examination revealed preexisting renal pathology in 76 patients (43%), including 34 out of 55 (62%) patients who had a decrease in glomerular filtration rate (GFR) at the time of hospitalization, and in 40 out of 165 (24%) patients who had normal kidney function at admission (P<0.01). The most common pathological feature responsible for kidney injury in the vast majority of cases was acute tubular necrosis. In some cases, tubular damage was associated with isometric vacuolization of the tubular epithelium. Most patients had also prominent capillaries and venular congestion with erythrocyte aggregates obstructing the lumen of peritubular and glomerular capillaries. Six patients with AKI (5.2%) had morphological features of thrombotic microangiopathy, accompanied by clinical manifestations (anemia, thrombocytopenia, increased LDH). Conclusion: acute kidney injury is a common complication of severe forms of coronavirus infection. The duration of mechanical ventilation is a significant predictor of its development. Thrombotic microangiopathy may be one of the rare causes of kidney damage in COVID-19.