Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum and soft tissue emphysema as complication in patients with COVID-19, series of cases.

Spontaneous pneumomediastinum, pneumothorax, pneumoperitoneum, and soft tissue emphysema have been recently described in several sources as possible complications in patients with severe COVID-19 and lung damage. This clinical case is dedicated to demonstrarte the development of these lesions in 3 male patients with comorbid conditions. The putative pathophysiological mechanism of these complications is air leakage due to extensive diffuse alveolar damage followed by rupture of the alveoli. All presented patients had a favorable outcome of the disease without lethal cases, their laboratory data and clinical dynamics were described. It should be noted that such conditions are not rare complications of COVID-19, and are observed mainly in male patients with severe form of the disease and the presence of comorbid conditions. Such complications are associated with long hospitalization and a severe prognosis. In some cases, with a mild course of the disease and positive dynamics in a decrease of the percentage of pulmonary lesions, the outcome is favorable, not requiring additional invasive interventions.Copyright © 2022 Medical Visualization. All rights reserved.

Multifactorial Effects of Covid-19: A Review of Published Autopsy Reports

Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.

Evaluation of Efficacy of the Amino Acid-Peptide Complex Administered Intragastrically to Golden Hamsters Experimentally Infected with Sars-Cov-2

The development of coronavirus infection outbreak into a pandemic, coupled with the lack of effective COVID-19 therapies, is a challenge for the entire pharmaceutical industry. This study aimed to assess the treatment and preventive efficacy of the amino acid-peptide complex (APC) in male Syrian hamsters infected with SARSCoV-2 (intranasal administration of 26 mul of the virus culture, titer of 4 x 104 TCD50/ml). In a modeled COVID-19 case, APC administered for treatment and preventive purposes reduced lung damage. Compared to the positive control group, test group had the lung weight factor 15.2% smaller (trend), which indicates a less pronounced edema. Microscopic examination revealed no alveolar edema, atypical hypertrophied forms of type II alveolocytes, pulmonary parenchyma fibrinization. The macrophage reaction intensified, which is probably a result of the APC-induced activation of regenerative processes in the lung tissues. Spleens of the animals that received APC for therapeutic and preventive purposes were less engorged and had fewer hemorrhages. The decrease of body weight of the test animals that received APC for treatment and prevention was insignificant (p < 0.05), which indicates a less severe course of COVID-19. Administered following a purely therapeutic protocol, APC proved ineffective against SARS-CoV-2 post-infection. Thus, APC-based drug used as a therapeutic and preventive agent reduces pulmonary edema and makes morphological signs of lung tissue damage less pronounced in male Syrian hamsters infected with SARS-CoV-2.Copyright © Extreme Medicine.All right reserved.

Lung pathology

The series of autopsies reported since the beginning of the pandemic have highlighted several patterns of lung damage, both isolated and combined. The factors influencing the occurrence of these different tissue responses to viral aggression by SARS-CoV-2 have not yet been determined. In asymptomatic patients or patients with respiratory symptoms who were not ventilated, lymphocyte pneumonia associated with type II pneumocyte atypical hyperplasia and a few hyaline membranes or focal lesions of acute fibrinous pneumonia have been observed. In critically ill patients, the most frequent pattern is diffuse alveolar damage with interstitial lymphoid infiltration, type II pneumocyte atypia and, very often, capillary or arteriolar microthromboses and/or endothelitis. The precise description of these lesions, which is becoming more and more consensual, makes it possible to understand the favourable effects of corticosteroid therapy in seriously ill patients and the evolution under ventilation towards fibrosis.Copyright © ERS 2021.

Description of the clinical picture of COVID-19 in patients with fatal outcome

In the Chelyabinsk region in 2020, 33 473 cases of a new coronavirus infection (COVID-19) were detected, of which 493 were fatal. The peak incidence of COVID-19 was recorded in November-December 2020. Purpose of research: description of the course of the infectious process of COVID-19 in patients with a fatal outcome. Material and methods. A retrospective analysis of case histories of patients with COVID-19 who had a lethal outcome was carried out using the method of continuous sampling from November 2020 to April 2021 on the basis of the Regional Infectious Diseases Center of the Regional Clinical Hospital No. 3 of the Chelyabinsk Region. Diagnosis was based on a comprehensive assessment of the anamnesis, clinical, laboratory and instrumental data in accordance with the Interim Guidelines "Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19)" version 9 dated 10/26/2020. Verification of the etiological diagnosis was carried out by PCR with reverse transcription to detect SARS-CoV-2 RNA in the nasopharyngeal secretion. The autopsy material was studied in the Pathoanatomical Department No. 9 of the Chelyabinsk Regional Pathological Bureau. Results and discussion. The average age of patients with a fatal outcome was 70 years, more often they were people with blood groups I and II, not vaccinated against COVID-19, pneumococcal infection and influenza;no gender differences were found. For patients with a fatal outcome from COVID-19, the presence of concomitant pathology is most characteristic: arterial hypertension (58%), atherosclerosis (45%), type 2 diabetes mellitus (41.5%), malignant neoplasms (17%). Among the "lethal patients", 50% had lung lesions at admission CT 2 and 25% had changes in the lungs consistent with CT 1;there was also a violation of cognitive functions in 21% of individuals. When comparing the analysis of studies of autopsy material and the clinical picture of patients, it was found that the morphological substrate of COVID-19 is both diffuse alveolar damage and simultaneous damage to the vascular bed, which is accompanied by damage to various organs and systems of the patient's body.Copyright © Eco-Vector, 2022.

Hospital in Crisis: The Story of Mass Communication Efforts during the Covid-19 Pandemic

Purpose of study The COVID-19 pandemic led to an unprecedented rapid transmission of healthcare information. This information was critical to enact frequently changing patient care protocols and to inform staff about redistribution of hospital resources at New York University Langone Hospital- Long Island. In this investigation, we analyze our hospital clinicians' methods of mass communication to front-line health care workers, with particular interest in assessing how communication was informed by real-time clinical findings. At the height of the pandemic (March 25th- April 15th), a mass broadcast email disseminated daily from the Director of Pulmonary and Critical Care was effective in informing treatment protocols that were clinically observed to improve patient outcomes. We analyzed over thirty broadcast emails and identified three major categories of information that were routinely addressed and/or updated: (i) reallocation of resources, (ii) clinical protocol changes, (iii) recommended lab tests for monitoring patient clinical course. We also interviewed key hospital clinicians and administrators on their experience working during the height of the pandemic. We found treatment protocols in these emails included information regarding the use of steroids and monoclonal antibody therapy, ventilators, and patient repositioning. In addition, the hospital's first autopsy results on COVID related deaths gave further insight into the disease process and manner of death for many patients (diffuse alveolar damage and evidence of hypercoagulability). So, too, did clinical findings around this time support what was seen grossly on autopsy-patients with more severe disease often presented with serial d-dimer levels >6x the normal limit. The information through these different conduits was synthesized and subsequently communicated in the aforementioned mass emails as an anticoagulation treatment protocol. Through continuous input of data, this protocol was updated and adjusted over the course of three weeks. We found that real-time communication amongst hospital staff regarding patient treatment protocols was a dynamic process that required synthesis of lab values, autopsy findings, and observed response to treatments. Successful treatment of patients depended on continuous review and communication of this information. Methods used The COVID-19 pandemic led to an unprecedented rapid transmission of healthcare information. This information was critical to enact frequently changing patient care protocols and to inform staff about redistribution of hospital resources at New York University Langone Hospital-- Long Island. In this investigation, we analyze our hospital clinicians' methods of mass communication to front-line health care workers, with particular interest in assessing how communication was informed by real-time clinical findings. At the height of the pandemic (March 25th- April 15th), a mass broadcast email disseminated daily from the Director of Pulmonary and Critical Care was effective in informing treatment protocols that were clinically observed to improve patient outcomes. Summary of results We analyzed over thirty broadcast emails and identified three major categories of information that were routinely addressed and/or updated: (i) reallocation of resources, (ii) clinical protocol changes, (iii) recommended lab tests for monitoring patient clinical course. We also interviewed key hospital clinicians and administrators on their experience working during the height of the pandemic. We found treatment protocols in these emails included information regarding the use of steroids and monoclonal antibody therapy, ventilators, and patient repositioning. In addition, the hospital's first autopsy results on COVID related deaths gave further insight into the disease process and manner of death for many patients (diffuse alveolar damage and evidence of hypercoagulability). So, too, did clinical findings around this time support what was seen grossly on autopsy- patients with more severe disease often presented with seri l d-dimer levels >6x the normal limit. The information through these different conduits was synthesized and subsequently communicated in the aforementioned mass emails as an anticoagulation treatment protocol. Through continuous input of data, this protocol was updated and adjusted over the course of three weeks. Conclusions We found that real-time communication amongst hospital staff regarding patient treatment protocols was a dynamic process that required synthesis of lab values, autopsy findings, and observed response to treatments. Successful treatment of patients depended on continuous review and communication of this information.

Histomorphological Spectrum of Lung Lesions at Autopsy-A Tertiary Care Centre Experience

Background and aims: A wide variety of pathological conditions involve the lungs. In autopsy, the lungs are examined for disease, injury and other findings suggesting cause of death or related changes.Aims & Objectives: The present study aimed to study the histomorphological spectrum of lung lesions at autopsy and to assess the frequency of different types of lesions;and to associate histomorphological changes with cause of death.Material and Methods: It was a one-year observational study conducted in the Department of Pathology, Govt. Medical College, Jammu. Lung tissue pieces from all medicolegal autopsies received were fixed, examined grossly, processed;paraffin embedded sections obtained were stained with Hematoxylin and Eosin stain and examined under microscope. Findings were recorded and tabulated. Result(s): Out of 264 cases, males were predominantly affected (84%);median age was 38 years. The various changes observed were congestion (68%), edema (45.4%), pneumonia (5%), granulomatous inflammation (3%), diffuse alveolar damage (1.5%), haemorrhage (14.4%), interstitial changes (60%), malaria (0.4%) and malignancy (0.4%). Natural deaths were the commonest cause (75, 28%) followed by asphyxial deaths (65, 24.6%). Conclusion(s): Histopathological examination of lung autopsies highlights many incidental findings, establishes underlying cause of death, serves as a learning tool and also holds scope for detection of newer diseases.Copyright © 2023 JK Science.

Pathology of Major Organs in Autopsy Specimens of Covid Positive Patients

Background: Pathological Autopsy has been the mainstay of understanding the concepts of diseases. Histopathological changes due to Covid 19 infection in various organs are not well documented, especially in the heart. Objective: Describe the histomorphology in major organs - heart, lung and brain in autopsy specimens of COVID positive patients. Determination of a possible pathophysiological outcome as cause of death. Materials and methods: Descriptive Cross-sectional Autopsy Study conducted in the Departments of Pathology and Forensic Medicine, Government Medical College, Manjeri over a one-year period. All RTPCR proven COVID positive deaths, irrespective of any other known / medicolegal cause of death were included in the study. Results: Eleven autopsy cases were studied in the 1-year period. Diffuse alveolar damage of Lung was observed in 2 of the eleven patients. 4 of the eleven patients had histologic findings consistent with Ischemic Heart Disease. The rest of the patients (5 in number) were 50 years and below and had no evidence of coronary artery disease. These cases had Myocarditis with myofiber loss in random sections. The youngest case in this series was 16 years of age. Conclusions: Cardiovascular disease appeared to be the major finding related to death in majority of COVID patients;this included Myocardial infarction as well as Myocarditis. COVID induced inflammatory changes in the heart appear to play a major role in its pathogenesis. [ FROM AUTHOR] Copyright of Journal of Cardiovascular Disease Research (Journal of Cardiovascular Disease Research) is the property of Journal of Cardiovascular Disease Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Rituximab in the Treatment of Idiopathic Inflammatory Myopathies with Interstitial Lung Disease, Long-Term Follow-Up

Background. Interstitial lung disease (ILD) is the common internal organ manifestation of idiopathic inflammatory myopathies (IIM) that can severely affect the course and prognosis of the disease. Rituximab (RTX) has been used to treat IIM, including variants with ILD. Objectives. To describe the course of disease in IIM patients with ILD, treated with RTX in long-term follow-up. Methods. Our prospective study included 35 pts with IIM fulfilling Bohan and Peter criteria and having ILD. The mean age was 51.8+/-11.9 years, female-26 pts (74%);24 (68.5%) with antisynthetase syndrome, 5 (14.3%) dermatomyositis (DM), 5 (14.3%) with a-Pm/Scl overlap myositis and 1 (2,9%) with a-SRP necrotizing myopathy were included. 25 (71,4% ) patients had nonspecific interstitial pneumonia, 9 (25,7%) organizing pneumonia (OP) and 1 (2,9%) OP, transformed to diffuse alveolar damage. All pts had the standard examination including manual muscle testing (MMT), creatinkinase (CK) anti-Jo-1 antibodies (anti-Jo-1) assay;forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) evaluation as well as high-resolution computed tomography (HRCT) scanning of the chest were performed at baseline, and 36 and more months. The median disease duration was 3.2 [0.16-18] years, 21 (60%) of pts were positive for a-Jo-1 antibody. All pts received prednisolone at a mean dose of 24.3+/-13 mg/day, immunosupressants at inclusion received 25 (71%) pts: cyclophosphamide 18 , mycophenolate mofetil 6 and comdination 1;Rituximab (RTX) was administered in case of severe course of disease and intolerance or inadequate response to GC and other immunosuppressive drugs. Results. The mean follow-up period after the first infusion of RTX was 47.2+/-11.9 months. Pts received 1-11 courses of RTX . The cumulative mean dose of RTX was 4.6 +/-2.5g. MMT 8 increased from 135.8+/-13.5 to 148.75+/-3.5 (p=0.000001). CK level decreased DELTACK - 762 u/l(median 340;25th% 9;75th% 821). anti-Jo-1 decreased from 173.4+/-37 to 96.5+/-79 u/ml (p=0.00002), FVC increased from 82+/-22.6 to 96,9+/-22% (p=0.00011). DLCO increased from 51.4+/-15.2 to 60+/-77.8% (p=0.0001). The mean prednisone dose was reduced from 24.3+/-13 to 5.7+/-2.4 mg/day. 3 pts died: ILD progression was the cause of death in 1 case, 1 bacterial pneumonia and COVID19 pneumonia. Conclusions. The results of this study confirm the positive effect of RTX in IIM patients with ILD (increase of muscle strength and improve lung function, decrease in anti-Jo-1 levels) and also its good steroid-sparing effect. RTX could be considered as an effective drug for the complex therapy of IIM patients with ILD when standard therapy is ineffective or impossible.

Morphological prediction of lethal outcomes in the evaluation of lung tissue structural changes in patients on respiratory support with СOVID-19: Ukrainian experience.

The impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on lung tissue in patients on respiratory support is of significant scientific interest in predicting mortality. This study aimed to analyze post-mortem histological changes in the lung tissue of COVID-19 patients on respiratory support using vital radiology semiotics. A total of 41 autopsies were performed on patients who died of SARS-CoV-2 and had confirmed COVID-19 by polymerase chain reaction (PCR) and radiological evidence of lung tissue consolidation and ground glass opacity. The results showed that the duration of COVID-19 in patients on respiratory support was significantly associated with the development of all stages of diffuse alveolar damage, acute fibrous organizing pneumonia, pulmonary capillary congestion, fibrin thrombi, perivascular inflammation, alveolar hemorrhage, proliferating interstitial fibroblasts, and pulmonary embolism. The prediction model for lethal outcomes based on the duration of total respiratory support had a sensitivity of 68.3% and a specificity of 87.5%. In conclusion, for COVID-19 patients on long-term respiratory support with radiological signs of ground glass opacity and lung consolidation, post-mortem morphological features included various stages of diffuse alveolar lung damage, pulmonary capillary congestion, fibrin clots, and perivascular inflammation.

Developing advanced cell culture models to study COVID19-associated pulmonary fibrosis

Patients with severe COVID-19-associated pneumonia are at risk to develop pulmonary fibrosis. To study the underlying mechanisms, we aim to develop advanced cell culture models that reliably reflect COVID-19-related profibrotic microenvironment. To identify key cellular players, we performed pilot immunohistochemistry analysis on lung tissue from COVID-19 patients with fibrosis collected during autopsy. Results revealed diffuse alveolar damage with macrophage infiltration, and myofibroblast accumulation with enriched collagen deposition surrounding the damaged alveoli. To mimic SARS-CoV-2 infection in alveoli, we infected human primary type II alveolar epithelial cells (AEC2) and found enhanced signaling of profibrotic cytokine transforming growth factor beta (TGFbeta) in some donors. To recreate the early fibrotic niche, an alveolar-macrophage-fibroblast (AMF) tri-culture model was established. After infecting AEC2 with SARS-CoV-2 in this AMF model, gene expression analysis provided evidence for fibroblast-to-myofibroblast transition. Furthermore, we found that overexpression of SARS-CoV-2 papain-like protease (PLpro) can promote TGFbeta signaling in HEK293T and A549 cells. After infecting AEC2 with SARS-CoV-2 PLpro lentivirus in the AMF model, we found signs of epithelial-to-mesenchymal transition and fibroblast-to myofibroblast transition. In future studies, we will use a detailed analysis of COVID-19-associated lung fibrosis with other types of lung fibrosis, to further refine COVID-19-related fibrosis models, including lung-on-chip models.

Phenotypes of post covid interstitial lung disease, clinical, radiological, and pathological correlations

Introduction: The clinical-radiologic-pathologic features of post-COVID interstitial lung disease (ILD) remain to be explored. Method(s): In a prospective multicenter Italian study (PCOILS), subsequent patients seen at 4-18 months after the acute infection underwent transbronchial lung cryobiopsy and BAL if they showed a significant ILD (progressive and/or symptomatic and/or with pulmonary function impairment). Result(s): 19 patients enrolled;characteristics are summarized in Fig.2. We identified 3 post-COVID phenotypes: 1) prominent vascular changes;2) post-COVID fibrosis;3) persistent COVID. Fig. 1. Phenotype 1 was detected only in 2 cases with similar characteristics as showed in Fig. 1 Phenotype 2 was detected in 7 patients all with HRCT NSIP/OP features. Histology showed fibrotic or mixed NSIP, fibrotic OP, fibrotic DAD and bronchiolar damage. Phenotype 3 was detected only in the case reported in Fig.1.The remaining 9 patients were reclassified as known ILDs and treated according to current guidelines. Conclusion(s): We identified 3 phenotypes of postcovid damage with heterogeneous pictures and leading to differenttreatment choices.

Dynamics and Heterogeneity of the Lung Immunopathology in Severe COVID-19

Background: The key impact of SARS-CoV-2 is its ability to cause a life-threatening infection in the lung. Aim(s): Using spatially resolved multiplex imaging the present study decodes the immunopathological complexity of severe COVID-19. Method(s): Autopsy lung tissue from 18 COVID-19 patients was used to map immune and structural cells in acute/exudative, intermediate and advanced diffuse alveolar damage (DAD) through multiplex immunohistochemistry and spatial statistical analyses. Cytokine profiling, viral, bacteria and fungi detection and transcriptome analyses were also performed. Result(s): All cases displayed concomitant patterns of DAD. The spatially resolved multiplex data revealed intricate patchworks of mm -size microenvironments representing distinct immunological niches. In-depth analysis of DAD areas revealed that the temporal/spatial DAD progression is associated with expansion of adaptive immune cells, macrophages, CD8 T cells, fibroblasts, angiogenesis and lymphangiogenesis. Viral load correlated positively with acute DAD and negatively with disease/hospital length. Cytokines correlated mainly with macrophages and CD8 T cells. Pro-coagulation and acute repair markers were enriched in acute DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Conclusion(s): Our unraveling of the spatio-temporal immunopathology in COVID-19 cases exposes the heterogeneous dynamics of acute viral infection and subsequent responses that occur side-by-side in the lungs. This complex disease feature has important implications for disease management and development of novel immunemodulatory treatments.

Differentially expressed genes in Diffuse Alveolar Damage (DAD) patterns of COVID-19

Severe COVID-19 induces DAD, a condition with temporal-spatial heterogeneity. We determined the differentially expressed genes (DEGs) in the histological patterns of DAD. Twelve fatal COVID-19 cases were classified in acute DAD (n=5) and intermediate/advanced (IA) DAD (n=7). Autopsy lung RNA was extracted from COVID-19 and 4 control cases. RNA sequencing was performed on the Illumina NovaSeq 6000. Enrichment analysis was performed with clusterProfiler using Genome-wide annotation for Human R package. GO terms and KEGG pathways were considered enriched if adjusted p<=0.05. Principal component analysis showed that IA-DAD samples were grouped, while acute DAD samples were scattered. The differential expression analysis between these two groups and the control cases revealed: 261 DEGs in the acute DAD (143 Up- and 53 Down-regulated), 244 DEGs in the IA- DAD tissues (67 Up- and 116 Down-regulated), and 61 DEGs were shared between them (45 Up- and 16 Downregulated). Patients with acute DAD had up-regulated genes related to oxidative phosphorylation, blood coagulation, megakaryocytes differentiation/regulation, and platelet degranulation/activation. Patients with IA-DAD had DEGs related to immunoglobulins and extracellular matrix. The shared up-regulated DEGs between both patterns are involved in innate and adaptive immune responses. We selected 3 DEGs in each DAD pattern for validation by realtime PCR. There were no differences in acute DAD DEGs, but DEGs overexpressed in intermediate DAD (COL3A1, IGLV3-19, IGHV1-58) were significantly higher. Genes related to thrombotic events occur at the acute stage of DAD, whereas immunoglobulin production and remodeling occur at later stages of DAD.

Immunohistochemical profile of cell cycle control, proliferation and differentiation proteins of the pulmonary atypical alveolar epithelium with COVID-19-induced diffuse alveolar damage as compared to pulmonary [lepidic-growth] adenocarcinoma.

We aim aim to compare immunophenotypic charac-teritics of atypical epithelium (AE) with COVID-19-induced diffuse alveolar damage (DAD) and pulmonary lepidic-growth adenocarcinoma, accounting for cell cycle control, proliferation and differentiation]. Methods. We examined pulmonary tissue specimens from twenty-four fatal cases of CO VID-19-induced acute respiratory damage syndrome confirmed by autopsy (Group 1) and four cases of pulmonary lepidic-growth adenocarcinoma (Group 2). Perpendicular dimensions of 10 nuclei were measured on the H&E slides, means of their sums of products (SPNM) were calculated. We have used p53, Ki67, pi6, p63 antibodies for immunohistochemical staining in each case. We evaluate colour intensity, rate of stained cells of AE and the product of these parameters. We evaluated separately Nuclear and cyto-plasmic staining (couple) and only cytoplasmic staining (cyt) for pi6 expression. We measured proliferative index only at KI-67 stained slides. U-test and Spearman rank correlation test were used for statistical analysis. Results. Expression of p63 was higher in group 1 (p=0.001), while pi6 was more frequently expressed in group 2 (p=0.002). We have found no statistically significant differences (p>0.1) in the p53 and Ki67 expression. Group 1 showed There was negative correlation between the number of days from onset of symptoms and the following variables: Ki67 (r=M).587, p=0.003);SPNM (r 0.406, p=0.049). Conclusion. The present study has shown heterogeneity in levels of cell cycle control expression, proliferation and differentiation of atypical epithelium in the pulmonary lep-idic-growth adenocarcinoma and CO VID-19-induced diffuse alveolar damage.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

PATHOMORPHOLOGICAL FEATURES OF ACUTE RESPIRATORY DISTRESS SYNDROME IN COMPETING LUNG DISEASES: COVID-19 AND SARCOIDOSIS

The COVID-19 pandemic is a worldwide problem. The clinical spectrum of SARS-CoV-2 infection varies from asymptomatic or paucity-symptomatic forms to conditions such as pneumonia, acute respiratory distress syndrome and multiple organ failure. Objective was to describe a clinical case of SARS-CoV-2 infection in the patient with sarcoidosis and cardiovascular pathology developing acute respiratory syndrome and lung edema. Material and methods. There were analyzed accompanying medical documentation (outpatient chart, medical history), clinical and morphological histology data (description of macro- and micro-preparations) using hematoxylin and eosin staining. Results. Lung histological examination revealed signs of diffuse alveolar damage such as hyaline membranes lining and following the contours of the alveolar walls. Areas of necrosis and desquamation of the alveolar epithelium in the form of scattered cells or layers, areas of hemorrhages and hemosiderophages are detected in the alveolar walls. In the lumen of the alveoli, a sloughed epithelium with a hemorrhagic component, few multinucleated cells, macrophages, protein masses, and accumulated edematous fluid were determined. Pulmonary vessels are moderately full-blooded, surrounded by perivascular infiltrates. Signs of lung sarcoidosis were revealed. Histological examination found epithelioid cell granulomas consisting of mononuclear phagocytes and lymphocytes, without signs of necrosis. Granulomas with a proliferative component and hemorrhage sites were determined. Giant cells with cytoplasmic inclusions were detected — asteroid corpuscles and Schauman corpuscles. Non-caseous granulomas consisting of clusters of epithelioid histiocytes and giant Langhans cells surrounded by lymphocytes were detected in the lymph nodes of the lung roots. Hamazaki–Wesenberg corpuscles inside giant cells were found in the zones of peripheral sinuses of lymph nodes. In the lumen of the bronchi, there was found fully exfoliated epithelium, mucus. Granulomas are mainly observed subendothelially on the mucous membrane, without caseous necrosis. Histological examination of the cardiovascular system revealed fragmentation of some cardiomyocytes, cardiomyocyte focal hypertrophy along with moderate interstitial edema, erythrocyte sludge. Zones of small focal sclerosis were determined. The vessels of the microcirculatory bed are anemic, with hypertrophy of the walls in small arteries and arterioles. Virological examination of the sectional material in the lungs revealed SARS-CoV-2 RNA. Conclusion. Based on the data of medical documentation and the results of a post-mortem examination, it follows that the cause of death of the patient R.A., 50 years old, was a new coronavirus infection COVID-19 that resulted in bilateral total viral pneumonia. Сo-morbidity with competing diseases such as lung sarcoidosis and cardiovascular diseases aggravated the disease course, led to the development of early ARDS and affected the lethal outcome. © 2022 Saint Petersburg Pasteur Institute. All rights reserved.

Insights into the lung microenvironment after severe COVID-19

The SARS-CoV-2 is the betacoronavirus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Severe COVID-19 affects approximately 10-15% of patients and results in prolonged morbidity and mortality. Little is known about the immunophenotypic changes of the lung parenchyma driven by the viral infection in patients who die of severe COVID-19. Ultrasound-guided lung biopsies (LB) were collected (IRB approval#1561/21) within few hours from death in 15 severe COVID-19 patients between November 2020 and January 2021, in two patients who underwent lung transplantation after COVID-19 and in one patient who had surgery for bacterial superinfection during COVID-19 disease. All samples underwent histologic and immunohistochemistry evaluation and molecular profiling using the nCounter Host Response and Coronavirus Panel plus. As controls, lungs from end-stage usual interstitial pneumonia (UIP;n=9) and from lobectomy for lung cancer (Norm;n=5) were used. Eleven lungs (61%) were positive for SARS-CoV-2 RNA. Signs of diffuse alveolar damage (DAD) were observed in 6 patients (30%). COVID-19 lungs showed a marked macrophage infiltration with M2 polarization compared with controls. Globally, COVID-19 lungs showed distinct molecular profiles from UIP or Norm lungs. Specifically, a marked upregulation of interferon-genes that was directly correlated with SARS-CoV-2 genes was seen in COVID-19 lungs. COVID-19-specific genes signatures (Log2FC >1.5;adj p<0.05) obtained using VENN diagram showed impairment of the STAT3-pathway accompanied by the upregulation of the NFkB signaling. Results herein provide new insights into lung alterations induced by severe COVID-19 and suggest novel potential targets for therapeutic intervention.

Histopathologic changes in lung tissue after Covid-19 pneumonia

Current knowledge of histopathological changes in Covid-19 pneumonia is mainly based on autopsy findings. There are few data on dynamics of lung lesions in vivo after acute phase of disease. The aim of this study was to determine histopathologic changes during the long/post-Covid stage in patients who had suffered from moderate to severe Covid-19 pneumonia. Bronchoscopy with transbronchial lung biopsy was performed in patients with HRCT lesions involving >40% of lung parenchyma, at least 4 weeks after discharge. Additional criteria were restrictive pattern in lung function tests and signed informed consent. Histopathologic analyses were performed using H&E, MSB, MOVAT, TTF1, CD34 and CD68 staining. Research was approved by the Hospital Ethical Committee. Among 26 patients that met inclusion criteria, adequate biopsy samples were obtained from 24. The mean time from the onset of disease to biopsy was 13 weeks. We found 4 histopathologic patterns: diffuse alveolar damage-DAD with vascular abnormalities, nonspecific interstitial inflammation, organizing pneumonia and interstitial fibrosis in 11, 9, 2 and 2 patients, respectively. Vascular abnormalities included capillary thrombi, dilated venules and dissection of small pulmonary arteries. Given the duration of disease, DAD and vascular abnormalities were detected up to the 12 week from the onset of symptoms. All patients biopsied after 12th weeks had some degree of tissue inflammation without vascular changes. Our findings show rather slow recovery of lung tissue after Covid-19 pneumonia. Long lasting DAD with vascular abnormalities may explain prolonged dyspnea and exercise intolerance and should be taken into consideration when planning further rehabilitation.

A study on the morbid histopathological changes in COVID-19 patients with or without comorbidities using minimally invasive tissue sampling

Introduction: COVID-19 causes morbid pathological changes in different organs including lungs, kidney, liver,etc especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without - not much is known about the differences at histopathological level. Aim(s): It was to compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised(Gr 1), malignancy(Gr 2) or had cardiometabolic conditions (hypertension, diabetes or coronary artery disease)(Gr 3). Method(s): Post-mortem tissue sampling (MITS) was done from the lungs, kidney, heart, and liver using biopsy gun within two hours of death. Routine (H & E stain) and special stains (AFB, SM, PAS) were done besides immunohistochemistry. Result(s): A total of 100 patients underwent MITS and data of 92 were included (immunocompromised: 27, maligancy:18, cardiometabolic conditions:71). Within lung histopathology, capillary congestion was more in those with malignancy while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia etc was equally distributed. Within liver, architecture distortion was significantly different in immunocompromised while steatosis, portal inflammation, Kupffer cell hypertrophy, confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological differences in heart was discerned. Conclusion(s): Certain histopathological features are markedly different in different groups (Gr 1,2 and3)of COVID-19 patients with fatal outcome.