Autopsy data from 80 patients who died of the COVID-19 infection were analysed. Using macro- and microscopic studies, specific features of pathological processes in various organs were identified. The obtained experimental data, along with information from literature sources, allowed conclusions to be drawn about the mechanisms of damaging internal organs and body systems, as well as assumptions to be made about individual links in the pathogenesis of COVID-19. The thanatogenesis of the disease and the main causes of death are discussed, including acute cardiopulmonary failure, acute renal failure, pulmonary thromboembolism, shock involving multiple organ failure and sepsis. The critical importance of autopsy is emphasized, which provides valuable information on the morphological substrate for this infection closely associated with possible clinical manifestations.

Against the background of a steady increase in the number of oncological diseases, as well as the complexity of the primary morphological diagnosis of malignant neoplasms (MNT) and precancerous conditions, especially in the regions of the Russian Federation, in 2019, the creation of a number of Reference Centers (RCs) for immunohistochemical, pathomorphological, molecular genetic methods was initiated research within the framework of the federal project “Fight against oncological diseases”. In 2020, on the basis of the centralized pathoanatomical department of the Clinical Center of Sechenov University, the RC began its work. Aim. To analyze the work of the RC of Sechenov University and compare the results obtained with the tasks of the federal project.Materials and methods. The data of histological, immunohistochemical studies from the registers of receipt of biopsy (surgical) materials and the issuance of the results of intravital pathoanatomical studies (account forms 014-2 / y and 057-y / 04), as well as data from the Telemedicine system of remote consultations, were analyzed. Results. For 21 months of work, the RC consulted 1476 requests received from 70 constituent entities of the Russian Federation. More than 10 % of reference diagnoses were made in a remote format through the Telemedicine system of remote consultations at the federal and regional levels using digital pathology techniques.Conclusion. Despite the obvious need for the work of RCs, there are still a number of issues that have a signifcant impact on the quality of diagnostic processes: specialization of specifc RCs, expansion of the range of incoming clinical and morphological diagnoses. It also requires attention to regularly improve the skills of RC employees in Russian and international educational systems and to equip the RC, frst of all, with virtual resources. The experience of the RC has demonstrated the importance of a second medical expert opinion in the primary diagnosis and verifcation of the diagnosis of malignant neoplasms of various localizations for the regions of the Russian Federation, where the acute problem is the general shortage of general pathologists and expert doctors.

Background:Levilimab (LVL) is a novel anti-IL6Rmonoclonal antibody against IL6Rα. Cytokine release syndrome plays the key role in the pathogenesis of a range of life-threatening conditions including the acute respiratory distress syndrome in severely ill COVID-19 patients. Thus, the use of LVL could be considered as anti-cytokine therapy with a potency to prevent the complications and progression of respiratory failure in COVID-19.Objectives:We analyzed the changes in the serum concentrations of inflammatory markers (Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-6) in patients treated with LVL or placebo as part of a phase III multicenter randomized double-blind placebo-controlled adaptive-design CORONA clinical study aimed to evaluate the efficacy and safety of LVL in subjects with severe COVID-19 (NCT04397562).Methods:A total of 217 patients were enrolled in the study, 206 patients were randomized, and 204 patients received the investigational product (IP, LVL or placebo).Study included men and non-pregnant women aged ≥18 years, hospitalized for severe COVID-19 pneumonia, receiving standard therapy according to the national guidelines. Patients with acute respiratory failure with the need in invasive respiratory support, septic shock, multiple organ failure or life expectancy less than 24 hours could not participate in the study. The use of other monoclonal antibodies and glucocorticoids for the treatment of COVID-19 were not allowed.Subjects were stratified according to the CRP level (CRP ≤ 7 mg/L; CRP > 7 mg/L) and then randomized (1:1) into 2 groups to receive LVL 324 mg or placebo. LVL/placebo were administered as a single subcutaneous injection, investigator and patients were unaware of the received therapy.Among secondary endpoints of the study changes from baseline in ESR, CRP and IL-6 concentrations were assessed. CRP level and ESR were measured before the IP administration and on Days 3, 5, 7, 14, 21, 29 and 30. Blood samples for the measurement of IL-6 concentration were obtained before the IP administration and then every day for 2 weeks after administration.Results:We observed the pronounced decrease of ESR in LVL group compared to Placebo group. The difference was statistically significant on Days 3 and 7: the median ESR change from baseline was -3 mm/h and +3 mm/h on Day 3, -11 mm/h and -3.1 mm/h on Day 7, in LVL and Placebo groups, respectively (p=0.0319 and p=0.0110, Days 3 and 7). The statistically significant difference in the change of CRP level was detected between the groups on Day 3: -26.6±41.9 mg/L and -19.2±58.2 mg/L in LVL and Placebo groups, respectively (p=0.0241). Numerically the same dynamics of ESR and CRP was observed over entire study period.The dynamics of IL-6 serum concentrations in LVL and Placebo groups was strikingly different. After LVL administration we detected the rapid significant increase in IL-6 concentration due to IL-6 receptors inhibition. Maximum change from baseline was observed on Day 3 (+91.9±117.7 pg/mL), on Day 14 the value was +31.9±62.7 pg/mL.In the Placebo group, the IL-6 concentration increased slightly until Day 4 (+5,1±76,5 pg/mL), and then decreased significantly (-39.2±55.1 pg/mL on Day 14) due to clinical improvement in this group.Conclusion:The significant differences in the dynamics of ESR, CRP and IL-6 after LVL administration compared to placebo confirmed the pharmacodynamic effect and its potency to prevent the excessive release of inflammatory substances in severely ill COVID-19 patients.References:[1]Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X, Zhang X, Pan A, Wei H. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. doi: 10.1073/pnas.2005615117. Epub 2020 Apr 29. PMID: 32350134; PMCID: PMC7245089.Acknowledgements:We thank all contributors to the CORONA study.Disclosure of Interests:Nikita Lomakin: None declared, Bulat Bakirov: None declared, Gaziiavdibir Musaev: None declared, Denis Protsenko: None declared, Olga Moiseeva: None declared, Elena Pasechnik: None declared, Vladimir Popov: None declared, Elena Smolyarchuk: None declared, Ivan Gordeev: None declared, Michail Gilyarov: None declared, Daria Fomina: None declared, V Mazurov: None declared, Maria Morozova Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Dmitrii Bogdan Employee of: JSC BIOCAD, Anton Lutskii Employee of: JSC BIOCAD, Arina Zinkina-Orihan Employee of: JSC BIOCAD, Iulia Linkova Employee of: JSC BIOCAD, Anton Seleznev Employee of: JSC BIOCAD.

On March 11, 2020, the World Health Organization declared COVID-19 apandemic. Despite a large number of scientific publications concerning the clinical picture and trea tment methods, data on structural changes of internal organs in COVID-19 is still insufficient. This review presents and analyzes several clinical cases published by research groups in various countries. COVID-19 infection is caused by a SARS-CoV-2 virus that binds to the angiotensin-converting enzyme 2 ACE2 receptor. Interaction with this receptor is the initial stage of pathogenesis. The morphological picture is similar to pneumonia caused by SARS-CoV and MERS-CoV: at the initial stage, a picture of shock lungs develops, later it ends in fibrosis and organizing pneumonia. One of the most severe complications is acute respiratory distress syndrome, which is observed in some clinical cases reviewed. In this article, we collected cases of clinical and morphological studies of patients with COVID-19, published in international peer-reviewed medical literature to date.

Time course of intermitochondrial contacts in rat cardiomyocytes is studied in myocardial hypertrophy followed by its regression, alcoholic cardiomyopathy, acute pancreatitis, and acute diffuse purulent peritonitis. Contacts between mitochondria do not depend on the type of disease. Subacute and chronic myocardial hyperfuntion is characterized by hyperplasia of contacts involving an increase in the number and extent of mitochondrial associations resulting from these contacts during exposure to a damaging factor and a decrease in the number of contacts and mitochondrial associations after liquidation of the cause of pathological process. In a severe disease (acute diffuse purulent peritonitis) the number of contacts between mitochondria drops and associations of damaged mitochondria disintegrate, causing exhaustion of cai-diae muscle energy. The results confirm Sarkisov's recombination theory that rearrangements of elements in biological system involve alterations of the quantity and quality of its function. This helps the heart overcome the critical stage of disease and later ensure hyperplasia of mitochondria and other structures in cardiomyocytes. This phenomenon possesses the characteristics of a biological regularity and is one of the earliest compensatory adaptive reactions of injured heart.