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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Kazan medical journal</journal-id><journal-title-group><journal-title xml:lang="en">Kazan medical journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Казанский медицинский журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0368-4814</issn><issn publication-format="electronic">2587-9359</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">88704</article-id><article-id pub-id-type="doi">10.17816/KMJ2022-575</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Theoretical and clinical medicine</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Теоретическая и клиническая медицина</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Pathological manifestations of inflammatory microthrombosis in COVID-19</article-title><trans-title-group xml:lang="ru"><trans-title>Патоморфологические проявления воспалительного микротромбоза при COVID-19</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8597-811X</contrib-id><contrib-id contrib-id-type="scopus">57201333953</contrib-id><contrib-id contrib-id-type="researcherid">AAT-8662-2020</contrib-id><contrib-id contrib-id-type="spin">2802-2405</contrib-id><name-alternatives><name xml:lang="en"><surname>Khismatullin</surname><given-names>Rafael R.</given-names></name><name xml:lang="ru"><surname>Хисматуллин</surname><given-names>Рафаэль Рафикович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>аспирант, каф. биохимии, биотехнологии и фармакологии; ст. препод., каф. морфологии и общей патологии, Институт фундаментальной медицины и биологии; врач-патологоанатом, Медсанчасть</p></bio><email>rafael.khismatullin@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8911-4818</contrib-id><name-alternatives><name xml:lang="en"><surname>Ivaeva</surname><given-names>Rozalina A.</given-names></name><name xml:lang="ru"><surname>Иваева</surname><given-names>Розалина Азгатовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., pathologist, Depart. of Pathology; Depart. of Morphology and General Pathology, Institute of Fundamental Medicine and Biology; Depart. of General Pathology</p></bio><bio xml:lang="ru"><p>препод., каф. морфологии и общей патологии, Институт фундаментальной медицины и биологии; асс., каф. общей патологии; врач-патологоанатом</p></bio><email>malina.93rozali@gmail.com</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7647-2966</contrib-id><contrib-id contrib-id-type="scopus">57223175877</contrib-id><name-alternatives><name xml:lang="en"><surname>Abdullayeva</surname><given-names>Shahnoza</given-names></name><name xml:lang="ru"><surname>Абдуллаева</surname><given-names>Шахноза</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>student, Institute of Fundamental Medicine and Biology</p></bio><bio xml:lang="ru"><p>магистрант, Институт фундаментальной медицины и биологии</p></bio><email>abdullayevashahnoza1599@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3366-5933</contrib-id><contrib-id contrib-id-type="scopus">8967918500</contrib-id><contrib-id contrib-id-type="spin">8856-5689</contrib-id><name-alternatives><name xml:lang="en"><surname>Shakirova</surname><given-names>Asia Z.</given-names></name><name xml:lang="ru"><surname>Шакирова</surname><given-names>Ася Закиевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., Cand. Sci. (Med.), Assoc. Prof., Depart. of General Pathology; pathologist, Depart. of Pathology</p></bio><bio xml:lang="ru"><p>канд. мед. наук, доц., каф. общей патологии; зав. отделением, врач-патологоанатом, патологоанатомическое отделение</p></bio><email>asgm12@list.ru</email><xref ref-type="aff" rid="aff3"/><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9164-0614</contrib-id><contrib-id contrib-id-type="scopus">57192931144</contrib-id><contrib-id contrib-id-type="spin">6961-7883</contrib-id><name-alternatives><name xml:lang="en"><surname>Khuzin</surname><given-names>Felix F.</given-names></name><name xml:lang="ru"><surname>Хузин</surname><given-names>Феликс Фаридович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., Cand. Sci. (Med.), Assoc. Prof., Depart. of Morphology and General Pathology, Institute of Fundamental Medicine and Biology</p></bio><bio xml:lang="ru"><p>канд. мед. наук, доц., каф. морфологии и общей патологии, Институт фундаментальной медицины и биологии</p></bio><email>felixhusin@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4460-4140</contrib-id><contrib-id contrib-id-type="scopus">8053304900</contrib-id><contrib-id contrib-id-type="researcherid">L-1976-2015</contrib-id><contrib-id contrib-id-type="spin">6000-3551</contrib-id><name-alternatives><name xml:lang="en"><surname>Kiassov</surname><given-names>Andrei P.</given-names></name><name xml:lang="ru"><surname>Киясов</surname><given-names>Андрей Павлович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., D. Sci. (Med.), Prof., Head of Depart., Depart. of Morphology and General Pathology, Institute of Fundamental Medicine and Biology</p></bio><bio xml:lang="ru"><p>докт. мед. наук, проф., зав. каф., каф. морфологии и общей патологии, директор, Институт фундаментальной медицины и биологии</p></bio><email>kiassov@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0643-1496</contrib-id><contrib-id contrib-id-type="scopus">35565337800</contrib-id><contrib-id contrib-id-type="researcherid">E-5291-2011</contrib-id><contrib-id contrib-id-type="spin">1327-1641</contrib-id><name-alternatives><name xml:lang="en"><surname>Litvinov</surname><given-names>Rustem I.</given-names></name><name xml:lang="ru"><surname>Литвинов</surname><given-names>Рустем Игоревич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>M.D., D. Sci. (Med.), Prof., Research Laboratory “Protein-Cellular Interactions”, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russia; Senior Research Investigator, Department of Cell and Developmental Biology, School of Medicine, University of Pennsylvania, Phi­ladelphia, USA</p></bio><bio xml:lang="ru"><p>докт. мед. наук, проф., главный научный сотрудник НИЛ «Белково-клеточные взаимодействия»; проф., каф. биохимии, биотехнологии и фармакологии, Институт фундаментальной медицины и биологии, Казанский (Приволжский) федеральный университет, г. Казань, Россия; ст. исследователь, Департамент клеточной биологии Медицинского факультета, Пенсильванский университет, Филадельфия, США</p></bio><email>litvinov@pennmedicine.upenn.edu</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University</institution></aff><aff><institution xml:lang="ru">Институт фундаментальной медицины и биологии Казанского (Приволжского) федерального университета</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Republican Clinical Hospital</institution></aff><aff><institution xml:lang="ru">Республиканская клиническая больница</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Kazan State Medical University</institution></aff><aff><institution xml:lang="ru">Казанский государственный медицинский университет</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">RZD-Medicine Clinical Hospital</institution></aff><aff><institution xml:lang="ru">Клиническая больница «РЖД-Медицина»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2022-08-15" publication-format="electronic"><day>15</day><month>08</month><year>2022</year></pub-date><volume>103</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>575</fpage><lpage>586</lpage><history><date date-type="received" iso-8601-date="2021-11-19"><day>19</day><month>11</month><year>2021</year></date><date date-type="accepted" iso-8601-date="2022-06-14"><day>14</day><month>06</month><year>2022</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2022, Eco-Vector</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2022, Эко-Вектор</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="en">Eco-Vector</copyright-holder><copyright-holder xml:lang="ru">Эко-Вектор</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/" start_date="2025-08-15"/></permissions><self-uri xlink:href="https://kazanmedjournal.ru/kazanmedj/article/view/88704">https://kazanmedjournal.ru/kazanmedj/article/view/88704</self-uri><abstract xml:lang="en"><p><bold>Background.</bold> COVID-19 is a predominantly respiratory disease caused by the SARS-CoV-2 virus that has spread as a pandemic since 2020; characterized by high mortality and unexplored long-term outcomes.</p> <p><bold>Aim.</bold> To describe the morphological changes in the lungs and other organs in severe forms of COVID-19.</p> <p><bold>Material and methods.</bold> A macro- and microscopic examination of the lungs, kidneys, liver, brain and heart of 45 patients who died from complications of COVID-19 was carried out. Histological preparations were stained with hematoxylin and eosin, by the Picro-Mallory stain, as well as with fluorescent antibodies and dyes to visualize neutrophil extracellular traps.</p> <p><bold>Results.</bold> The leading pathomorphological manifestations of COVID-19 were inflammation and microthrombosis in the lungs. At the same time, diffuse alveolar damage often developed as a manifestation of acute respiratory distress syndrome in an adult. Diffuse leukocyte infiltration of the lungs was combined with the formation of neutrophil extracellular traps in the lumens of the blood vessels. Diffuse microthrombi were found in most lung tissue samples (87%), while macroscopic thrombi were much less common (16%). In single cases, the cause of death was thromboembolism of the branches of the pulmonary artery, originating from deep vein thrombi of the lower extremities or the right atrial appendage. In the tissues of the liver, heart, kidneys and brain, moderate alterative (degenerative and necrobiotic) microscopic changes were observed, as well as morphological signs of concomitant chronic diseases.</p> <p><bold>Conclusion.</bold> COVID-19 is characterized by pathogenically interrelated morphological manifestations of inflammation and primary pulmonary (micro)thrombosis in the form of accumulation of leukocytes both in blood clots and in the alveoli, while regional pulmonary immunothrombosis is associated with diffuse damage to the alveoli; in the heart, brain, liver and kidneys, predominantly dystrophic and necrobiotic changes occur, which are typical of secondary injuries and/or concomitant pathology.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Актуальность.</bold> COVID-19 — преимущественно респираторное заболевание, вызываемое вирусом SARS-CoV-2 и принявшее в 2020 г. характер пандемии; характерны высокая смертность и неизученность отдалённых последствий.</p> <p><bold>Цель.</bold> Описать морфологические изменения в лёгких и других органах при тяжёлых формах COVID-19.</p> <p><bold>Материал и методы исследования.</bold> Проведено макро- и микроскопическое исследование лёгких, почек, печени, головного мозга и сердца 45 пациентов, умерших от осложнений COVID-19. Гистологические препараты окрашивали гематоксилином и эозином, по пикро-Маллори, а также флюоресцентными антителами и красителями для визуализации нейтрофильных внеклеточных ловушек.</p> <p><bold>Результаты.</bold> Ведущими патоморфологическими проявлениями COVID-19 были воспаление и микротромбоз в лёгких. При этом часто развивалось диффузное повреждение альвеол как проявление острого синдрома респираторного расстройства (дистресса) у взрослого. Диффузная лейкоцитарная инфильтрация лёгких сочеталась с образованием в просвете сосудов нейтрофильных внеклеточных ловушек. В большинстве образцов тканей лёгких (87%) обнаружены диффузные микротромбы, в то время как макроскопические тромбы встречались значительно реже (16%). В единичных случаях причиной смерти стала тромбоэмболия ветвей лёгочной артерии, происходящая из тромбов глубоких вен нижних конечностей или ушка правого предсердия. В тканях печени, сердца, почек и головного мозга присутствовали умеренные альтеративные (дистрофические и некробиотические) изменения, а также морфологические признаки сопутствующих хронических заболеваний.</p> <p><bold>Вывод.</bold> COVID-19 характеризуется патогенетически взаимосвязанными морфологическими проявлениями воспаления и первичного (микро)тромбоза лёгких в виде аккумуляции лейкоцитов как в составе тромбов, так и в альвеолах, при этом регионарный иммунотромбоз лёгких ассоциирован с диффузным повреждением альвеол; в сердце, головном мозге, печени и почках происходят преимущественно дистрофические и некробиотические изменения, типичные для вторичных повреждений и/или сопутствующей патологии.</p></trans-abstract><kwd-group xml:lang="en"><kwd>thrombosis</kwd><kwd>COVID-19</kwd><kwd>inflammation</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>тромбоз</kwd><kwd>COVID-19</kwd><kwd>воспаление</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution xml:lang="ru">Работа выполнена за счёт средств Программы стратегического академического лидерства (Приоритет-2030) Казанского (Приволжского) федерального университета, гранта Российского научного фонда 21-75-00010 и грантов Российского фонда фундаментальных исследований 19-015-00075 и 20-015-00257</institution></institution-wrap></funding-source></award-group><funding-statement xml:lang="en">This work was supported by the Strategic Academic Leadership Program (Priority-2030) of Kazan (Volga Region) Federal University, Russian Science Foundation grant 21-75-00010 and Russian Foundation for Basic Research grants 19-015-00075 and 20-015-00257.</funding-statement><funding-statement xml:lang="ru">Работа выполнена за счёт средств Программы стратегического академического лидерства (Приоритет-2030) Казанского (Приволжского) федерального университета, гранта Российского научного фонда 21-75-00010 и грантов Российского фонда фундаментальных исследований 19-015-00075 и 20-015-00257.</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. 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