Management of the activity of the Moscow pathology and anatomical service in the context of a pandemic of a new coronavirus infection in 2020–2022

The management of the activity of the pathology and anatomical service (PAS) of the Moscow Healthcare Department (DZM) in the context of the COVID-19 pandemic and the provision of timely and accurate pathological diagnostics, as well as the receipt of reliable statistics on mortality rate, made it possible to provide timely management decisions to combat the pandemic. Purpose. To present the successful experience of managing the activities of the Moscow Pathoanatomic Service of DZM in the conditions of a pandemic of a new coronavirus infection. Methods. The paper analyzes and summarizes the features of the activity of PAS of DZM in the conditions of the COVID-19 pandemic, presents the main activities carried out to ensure timely and accurate diagnostics in anatomical pathology, and obtaining reliable statistical data on mortality, demonstrates the most important management decisions for organizing work aimed at combating the pandemic. Analytical, organizational, and statistical research methods are used in the work. Results. In order to improve the organization of the work of PAS of DZM in the context of the COVID-19 pandemic and ensure timely and accurate pathological diagnostics, and obtaining reliable statistics on mortality from it, a number of important activities were carried out including reprofilation of the PAS and reorganization of the work of PAS of DZM, reorganization and optimization of the work of the organizational and methodological department for pathological anatomy (OMO PA) of the Research Institute for Healthcare Organization and Medical Management of Moscow Healthcare Department, carrying out activities to establish interaction between the chief specialist in pathological anatomy and OMO PA with the DZM, the Rosstat and the egistry Office in Multiple functional Centres, connection of all Departments of Pathology by the new laboratory information system «LABFORS», development of continuing medical education. Limitations. Limited time period for description;there is no comparison with other subjects;conditions of the COVID-19 epidemic. Conclusions. Thus, the PAS of DZM, under the guidance of the chief specialist in pathological anatomy of DZM and OMO PA, showed its efficiency and effectiveness in the context of a pandemic of a new coronavirus infection, successfully implemented new technologies and organizational principles, improved the organization of its work, developed both post-mortem and intravital diagnostics of diseases in anatomical pathology. © 2022 Izdatel'stvo Meditsina. All rights reserved.

[Features of the cell composition of inflammatory infiltrate in different phases of diffuse alveolar lung damage with COVID-19]. / Osobennosti kletochnogo sostava vospalitel'nogo infil'trata v raznye fazy diffuznogo al'veolyarnogo povrezhdeniya legkikh pri COVID-19.

BACKGROUND: Acute respiratory distress syndrome (ARDS) with COVID-19 has a worse prognosis than ARDS with other diseases. Mortality from ARDS with COVID-19 is 26.0 - 61.5%, and due to other causes - 35.3-37.2%. OBJECTIVE: To find of the correlation between polymorphonuclear leukocytes (PMNs), lymphocytes, and macrophages in the cellular composition of the inflammatory infiltrate at different stages and phases of diffuse alveolar damage (DAD) with COVID-19, analyzing the autopsy material. MATERIAL AND METHODS: The lung tissue of 25 patients who died from ARDS with COVID-19 without a secondary bacterial or mycotic infection, another thanatologically significant pathology of the lungs, was studied. To study the cellular composition of the inflammatory infiltrate and the dynamics of its changes a double immunohistochemical analysis of the expression of antibodies to CD15, CD3, and CD68 was used. RESULTS: The inflammatory infiltrate and intraalveolar exudate in the exudative phase of DAD was represented by 56.8% of PMNs (CD15-positive cells; hereinafter - the average value of the percentage of positive cells to the total number of cells of the inflammatory infiltrate), 6.9% - lymphocytes (CD3-positive cells) and 19.5% macrophages (CD68-positive cells). In the early stage of the proliferative phase: 14.1% PMNs, 38.7% lymphocytes and 13.5% macrophages. In the late stage of the proliferative phase: 11.3% PMNs, 14.5% lymphocytes and 39.3% macrophages. CONCLUSIONS: In the exudative phase of DAD a statistically significant predominance of PMN was revealed, which could determine the main volume of lung damage and the severity of ARDS with COVID-19. In the early stage of the proliferative phase of DAD, a statistically significant change in the composition of the inflammatory infiltrate was revealed to compare with the exudative phase: a significant decrease in the content of PMNs relative to the total number of cells in the inflammatory infiltrate; an increase in the number of lymphocytes, which is probably associated with the start of organization and repair processes. In the late stage of the proliferative phase of DAD, compared with its early stage, was revealed a statistically significant increase in the number of macrophages in ratio.

Long term pathological changes in lungs after COVID-19

World literature is paying increasing attention to the long-term course of COVID-19 and symptoms that appear after the acute coronavirus infection. The symptoms, functional state of the lungs, and the X-ray changes are assessed. Nevertheless, post-COVID lung histology has not been described yet. The aim of this article is to study the long-term pathological changes in the lungs after acute COVID-19. Methods. We analyzed autopsy lung material from 19 deceased who had COVID-19. The average age of the deceased was 68.82 ± 14.6 years. All patients were found to have IgG to SARS-CoV-2. The median time to death following viral interstitial pneumonia was 72 days. Results. The causes of death and thrombotic complications (infarctions of various organs and venous thrombosis) were analyzed. Histological examination revealed thrombosis of small pulmonary arteries and capillaries of interalveolar septa, microinfarctions, hemorrhages, foci of organizing pneumonia, and nonspecific interstitial pneumonia. Conclusion. The first assessment of histological changes in human lungs showed that the most common post-COVID pathologic changes are microcirculation disorders combined with small areas of acute lung damage. The obtained data are essential for understanding the pathogenesis of post-COVID syndrome, necessitate diagnostic of microvasculature disorders using laboratory tests, scintigraphy, and CT imaging, as well as search for the therapeutic strategies. © 2021 Vestnik Tomskogo Gosudarstvennogo Universiteta, Matematika i Mekhanika. All rights reserved.

Consensus position of endocrinologists and pathologists on coding causes of death in patients with diabetes mellitus (expert opinion)

Coding of the causes of death of patients with diabetes mellitus (DM) in the Russian Federation is one of the long-discussed problems, due to the comorbidity of diabetes and cardiovascular diseases (CVD) and a number of contradictions in the key regulatory documents regulating the statistics of mortality in this category of patients, which acquires particular relevance in the context of the coronavirus pandemic, due to its negative impact on the outcomes of the course of COVID-19 and mortality risks. In pursuance of the decisions of the Minutes of the meeting of the working group under the project committee of the National Project «Health» on identifying patterns in the formation of mortality rates of the population dated January 20, 2021 No. 1, chaired by Deputy Prime Minister of the Russian Federation T.A. Golikova, experts of two directions - endocrinology and pathological anatomy, prepared a Draft of agreed recommendations on the Rules for coding the causes of death of patients with diabetes, causing the greatest problems in terms of the use of ICD-10 when choosing the initial cause of death, including in the case of death from CVD and COVID-19.

Pathological Features in 100 Deceased Patients With COVID-19 in Correlation With Clinical and Laboratory Data.

Background: Autopsies on COVID-19 deceased patients have many limitations due to necessary epidemiologic and preventative measures. The ongoing pandemic has caused a significant strain on healthcare systems and is being extensively studied around the world. Clinical data does not always corelate with post-mortem findings. The goal of our study was to find pathognomonic factors associated with COVID-19 mortality in 100 post-mortem full body autopsies. Materials and Methods: Following necessary safety protocol, we performed 100 autopsies on patients who were diagnosed with COVID-19 related death. The macroscopic and microscopic pathologies were evaluated along with clinical and laboratory findings. Results: Extensive coagulopathic changes are seen throughout the bodies of diseased patients. Diffuse alveolar damage is pathognomonic of COVID-19 viral pneumonia, and is the leading cause of lethal outcome in younger patients. Extrapulmonary pathology is predominantly seen in the liver and spleen. Intravascular thrombosis is often widespread and signs of septic shock are often present. Conclusion: The described pathological manifestations of COVID-19 in deceased patients are an insight into the main mechanisms of SARS-CoV-2 associated lethal outcome. The disease bears no obvious bias in severity, but seems to be more severe in some patients, hinting at genetic or epigenetic factors at play.

A targeted study of pulmonary pathology and chest computed tomography (ct) findings in COVID-19

Introduction. In the context of the COVID-19 pandemic, one of the most important diagnostic methods is highresolution computed tomography of the lungs (HRCT), which is highly sensitive for diagnostics of viral pneumonia. Because of a variety of radiological changes in the lungs at different periods of the disease, it became necessary to compare the changes detected by HRCT with morphological features of the disease. The aim of the research is to compare the HRCT patterns and histological changes in the lungs in the deceased with COVID-19. Material and methods. We analyzed 45 pieces from 14 deceased with COVID-19 (7 men/7 women), with an average age of 77.1 ± 12.9 (49-90 years), which underwent HRCT no more than 5 days before death. On the fixed whole lungs, tissue sites were selected, according to the target localization selected by HRCT with 3- D reconstruction. The leading HRCT patterns such as 'ground glass' opacities, “crazy paving”, consolidation, and symptoms typical for organizing pneumonia were the points of interest. We performed routine hematoxylineosin stains for histopathologic evaluation. Results. “Ground glass” opacities in the majority of cases (57.1%) corresponded to an acute phase of diffuse alveolar damage (DAD) (intraalveolar edema, hyaline membranes, cellularity, interstitial infiltration). Mosaic histological changes with alternation of filled alveoli (intraalveolar edema, clusters of red blood cells, macrophages, lymphocytes, fibrin) and aerated alveoli were detected in the areas of “crazy paving” zones. Areas of consolidation were histologically represented by extensive intraalveolar hemorrhages and/or hemorrhagic infarcts in 45.5% of cases. Perilobular consolidation, subpleural cords, symptoms of “halo” and “reverse halo”, which we considered as part of the symptom complex of organizing pneumonia in 43% of cases morphologically corresponded to organizing pneumonia (the proliferative phase of DAD) and to distelectases. Conclusion. Herein, we established the correspondence of DAD histology phases with/ or without pulmonary intravascular coagulopathy to the main HRCT-patterns of viral pneumonia. The results obtained can be used to determine therapeutic tactics at different phases of viral pneumonia in COVID- 19.

Lung lesions in 4 pregnant women with severe covid-19-autopsy case

Currently, there are only scarce data on pulmonary COVID-19 lesions in pregnant women in the literature although the disease hasn't spared any country. This study aimed to provide insight into this issue. We carried out a retrospective analysis of the clinical data, autopsy, and microscopic findings in 4 pregnant women with severe COVID-19. Patients were admitted 4-5 days after COVID-19 onset with fever, dry cough, and reduced saturation. Positive SARSCoV2 nasopharyngeal swab PCRs were obtained. Chest CT revealed bilateral 'ground glass' pneumonia, CT 3-4. The women were diagnosed with severe COVID-19 requiring ALV and ECMO. They underwent emergent C-section with subsequent therapy. Patient 1, 37 y.o., 28-29 gestation weeks (GW), had comorbid conditions-obesity and arterial hypertension, died on the 11th bed-day (BD) due to pulmonary embolism. Patient 2, 31 y.o., 27 GW, developed bacterial pneumonia and acute pansinusitis with multiple organ failure resulting in death on 15th BD. Patient 3, 22 y.o., 35 GW, had ventilatorassociated pneumonia, lymphopenia, thrombocytopenia, anemia, and phlebothrombosis as COVID-19 complications. Later, she developed sepsis, which resulted in a lethal outcome (on 26th BD). Patient 4, 38 y.o., 32 GW, was diagnosed with pneumothorax on the 10th BD requiring pleural cavity drainage. The disease was complicated by bacterial pneumonia leading to respiratory failure and death (on the 30th BD). At autopsy, all four women had 'shock lungs' and diffuse alveolar damage at microscopy. Microscopic evaluation of the 1st patient's lung specimens revealed hyaline membranes corresponding to exudative DAD phase combined with proliferative DAD signs. In the 2nd case, we observed a pronounced cytopathic effect resulting in 'ugly' multinucleated cell formation, and multiple hemosiderophages in the alveolar lumens, as well as alveolar and bronchial metaplasia, confirmed by positive CK5-6 IHC staining. Third patient lung specimens demonstrated organizing viral pneumonia (with interalveolar granulation tissue, numerous interalveolar siderophages, indicating an alveolar-hemorrhagic syndrome) combined with massive bacterial pneumonia. Organizing viral pneumonia with mature interalveolar granulation tissue and sarcoid-like granulomas was diagnosed in 4 patient. Clinical and morphological analysis demonstrated that COVID-19 pneumonia features are similar for pregnant and non-pregnant patients of the same age group. The proliferative DAD phase was detected in three of 4 cases. However, of special interest is the first case, in which a combination of DAD phases was determined. At the same time, no severe obstetric complications were identified, which we associate with the timely diagnosis and prevention measures.

Acute kidney injury in COVID-19: clinical and morphological comparisons based on autopsy data

Severe Acute Respiratory Syndrome (SARS-CoV-2) has spread rapidly throughout the world, causing high morbidity and mortality. Analysis of clinical and autopsy data may allow to understand this disease. The results of pulmonary and renal autopsies in 37 deceased patients from COVID-19 are presented. Materials and methods. An autopsy was performed in Moscow in 37 deceased patients aged from 28 to 94 years. The microscopic features of the lungs and kidneys were examined using hematoxylin and eosin staining. Results. Important findings include diffuse alveolar injury, pulmonary thrombosis and microangiopathy, as well as acute kidney injury in all cases, varying in severity. Conclusions. We report the presence of acute kidney injury in all cases, which requires correction of renal function in patients with SARS-CoV-2, with control of serum creatinine levels, urine volume, proteinuria and hematuria. Тяжелый острый респираторный синдром (SARS-CoV-2) быстро распространился по всему миру, вызвав высокую заболеваемость и смертность. Анализ клинических данных и данных аутопсии может помочь нам разобраться в данной болезни. Мы представляем результаты легочной и почечной аутопсии у 37 умерших от COVID-19 пациентов. Материалы и методы. В Москве произведена аутопсия 37 умершим пациентам в возрасте от 28 до 94 лет. Были исследованы микроскопические особенности легких и почек с помощью окрашивания гематоксилином и эозином. Результаты. Важные результаты включают диффузное альвеолярное повреждение, тромбоз и микроангиопатию в легких, а также острое повреждение почек во всех случаях различной степени тяжести. Выводы. Мы сообщаем о наличии острого повреждения почек во всех исследуемых случаях, что требует коррекции функции почек у больных SARS-CоV-2 с контролем уровня креатинина в плазме крови, объема мочи, наличия протеинурии и гематурии.

Analysis of the first fatal outcome cases of a new coronavirus infection covid-19 in medical organizations of the state healthcare system of Moscow

COVID-19 posed a new challenge to the global medical science, and not all traditional approaches used earlier, for example, in the treatment of SARS and other viral infections, were acceptable. On March 20, 2020, the first fatal outcome from a new coro-navirus infection was registered in Moscow. By the time the article was published (6 weeks later) more than 1000 deaths were reg-istered. Taking into account the fact that there is still a growth in the number of patients and, consequently, deaths, the analysis of lethal outcomes of the first (in chronological order of patients) seems to be extremely relevant. As information about a new coro-navirus infection accumulates, our actions and recommendations on its treatment will change. Most drugs to treat the new coro-navirus infection are still under clinical trials. A vaccine has not been developed, and data on the use of plasma, convalescents, hydroxychloroquine and a number of other drugs are insufficient to provide recommendations that meet the principles of evidence-based medicine. We believe that the analysis of the first 157 fatal cases of a new coronavirus infection is only the first step in the for-mation of carefully verified treatment recommendations. © 2020, Media Sphera Publishing Group. All rights reserved.

[Acute kidney injury in COVID-19: clinical and morphological comparisons based on autopsy data]

Severe Acute Respiratory Syndrome (SARS-CoV-2) has spread rapidly throughout the world, causing high morbidity and mortality. Analysis of clinical and autopsy data may allow to understand this disease. The results of pulmonary and renal autopsies in 37 deceased patients from COVID-19 are presented. MATERIALS AND METHODS: An autopsy was performed in Moscow in 37 deceased patients aged from 28 to 94 years. The microscopic features of the lungs and kidneys were examined using hematoxylin and eosin staining. RESULTS: Important findings include diffuse alveolar injury, pulmonary thrombosis and microangiopathy, as well as acute kidney injury in all cases, varying in severity. CONCLUSIONS: We report the presence of acute kidney injury in all cases, which requires correction of renal function in patients with SARS-CoV-2, with control of serum creatinine levels, urine volume, proteinuria and hematuria.

Features of pathological anatomy of lungs at COVID-19

The research aim is to study the morphological features of COVID-19 in the lungs of patients who died in Moscow from March 20 to June 6, 2020. Methods. Autopsy material of the lungs from 123 deceased (54 women, 69 men) with COVID-19 coronavirus infection (confirmed by PCR) was analyzed, the median age was 71 (30 - 94) years, and the duration of the disease was 14 (3 - 65) days. In all cases, the patient's medical records and autopsy reports were analyzed. Macro- and microscopic changes in the lungs were evaluated in all the observations. Results. The pathology of the lungs in COVID-19 corresponds to various phases of diffuse alveolar damage (DAD). The exudative phase of DAD was detected in 54 (43.9%), the proliferative phase - in 21 (14.63%), and their combination - in 51 (41.46%) of the deceased. Histological features of different phases of DAD are described. Conclusion. An analysis of autopsy material revealed a mismatch between the duration of the course of the disease and the phase of diffuse alveolar damage. A significant portion of the dead found a combination of exudative and proliferative phases of the disease. Histological signs that indirectly indicate a violation of the coagulation system during COVID-19 are described. © 2020 Medical Education. All rights reserved.

Prediction of lethal outcomes in COVID-19 cases based on the results chest computed tomography

The objective: to predict lethal outcomes in patients with COVID-19 based on the result of chest computed tomography (chest CT) using a semi-quantitative visual scale of the pulmonary parenchyma lesion. Subjects and methods. Inclusion criteria: patients who underwent chest CT from March 2 to May 1, 2020, inclusively, upon referral of a general practitioner due to suspected community-acquired pneumonia caused by COVID-19. Chest CT was performed in 48 medical organizations providing primary medical care to the adult population in Moscow. Exclusion criteria: patients whose chest CT was not assessed by CT 0-4 score;patients who were not confirmed as COVID-19 positive. In the Russian Federation, CT 0-4 score is recommended to be used for assessment of the extent of lung parenchyma lesion in cases with suspected COVID-19. Data on fatal outcomes were received on May 4, 2020 inclusive. Results: data of 13,003 patients from the Unified Radiological Information Service were retrospectively included in the study according to inclusion and exclusion criteria. The test aimed to detect a trend of directional changes in the proportion of deceased patients among various categories using CT 0-4 score demonstrated a statistically significant result (p < 0.0001). The chance of a lethal outcome increases directionally from CT-0 to CT-4. The test for deviations from the linear trend also provided p < 0.0001, i.e. when moving to higher scores (CT-3 and CT-4), there was an accelerated increase in the risk of death. Analysis of overall survival using the Cox regression model showed that the assessed factors (age and CT 0-4 score) were statistically significantly associated with the time to death from COVID-19 (p < 0.05). The risk of death increased with age, on average, 8.6% for every 5 years (95% CI 0.8-17.0%). When transferring from one category of CT to the next one, the risk increased by 38% on the average (95% CI 17.1-62.6%). There was no statistically significant association of gender factor with overall survival (p = 0.408). The visual score of CT 0-4 recommended for use in the Russian Federation to assess lung parenchyma lesions according to chest CT data, is a predictor of a lethal outcome in patients with COVID-19. CT 0-4 score is convenient for practical use. Цель исследования: прогнозирование летальных исходов у больных COVID-19 по данным компьютерной томографии органов грудной клетки (КТ ОГК) с помощью полуколичественной визуальной шкалы степени поражения легочной паренхимы. Материалы и методы. Критерии включения: пациенты, которым с 2 марта по 1 мая 2020 г. включительно проведена КТ ОГК по направлению врача-терапевта с подозрением на внебольничную пневмонию, вызванную COVID-19. Эти исследования были выполнены в 48 медицинских организациях, оказывающих первичную медицинскую помощь взрослому населению в Москве. Критерии исключения: пациенты, у которых КТ ОГК не оценена по категориям шкалы «КТ 0-4»;пациенты, у которых COVID-19 не подтвердился. Шкала «КТ 0-4» рекомендована к применению в РФ для оценки объема поражения паренхимы легкого при подозрении на COVID-19. Данные о летальных исходах были получены на 4 мая 2020 г. включительно. Результаты: ретроспективно из Единого радиологического информационного сервиса на основании критериев включения и исключения для исследования отобраны данные 13 003 пациентов. Тест на наличие тенденции направленного изменения доли умерших пациентов среди различных категорий по шкале «КТ 0-4» дал статистически значимый результат (p < 0,0001). Вероятность летального исхода направленно увеличивается от «КТ-0» до «КТ-4». Тест на отклонения тренда от линейности также дал p < 0,0001, то есть при переходе к более высоким категориям («КТ-3» и «КТ-4») происходит ускорение прироста риска летального исхода. Анализ по общей выживаемости с помощью регрессионной модели Кокса показал, что оцениваемые факторы (возраст и категория по шкале «КТ 0-4») были статистически значимо ассоциированы со временем до наступления смерти от COVID-19 (p < 0,05). Риск смерти увеличивался с возрастом в среднем на 8,6% на каждые 5 лет (95%-ный ДИ 0,8-17,0%). При переходе из одной категории КТ в следующую риск увеличивался в среднем на 38% (95%-ный ДИ 17,1- 62,6%). Статистически значимой ассоциации фактора пола с общей выживаемостью не выявлено (p = 0,408). Визуальная шкала «КТ 0-4», рекомендованная в РФ для оценки поражения паренхимы легкого по данным КТ, является предиктором смерти у пациентов с COVID-19. Шкала «КТ 0-4» удобна для практического применения.