{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:36:37Z","timestamp":1760229397605,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2022-301"],"award-info":[{"award-number":["075-15-2022-301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>In spite of intensive studies of different aspects of a new coronavirus infection, many issues still remain unclear. In a screening analysis of histopathology in l200 lethal cases, authors succeeded in performing a wide spectrum of immune histochemical reactions (CD2, CD 3, CD 4, CD 5, CD 7, CD 8, CD14, CD 20, CD 31, CD 34, CD 56, CD 57, CD 68, CD 163, collagen 1,3, spike protein SARS-CoV-2, caspase-3, MLCM; ACE2 receptor, occludin, and claudin-1 and -3) and electron microscopy. The results of the histological and IHC studies of deceased people with varying degrees of severity of coronavirus infection confirmed the ability of these pathogens to cause cytoproliferative changes, primarily in epithelial and endothelial cells. Lesions of various organs are possible, while the reasons for significant differences in organotropy remain unclear. Severe respiratory failure in COVID-19 in humans is associated with a very peculiar viral pneumonia. In the pathogenesis of COVID-19, the most important role is played by lesions of the microcirculatory bed, the genesis of which requires further study, but direct viral damage is most likely. Endothelial damage can be associated with both thrombosis in vessels of various calibers, leading to characteristic complications, and the development of DIC syndrome with maximal kidney damage. Such lesions can be the basis of clinically diagnosed septic shock, while usually there are no morphological data in favor of classical sepsis caused by bacteria or fungi. A massive infiltration of the lung tissue and other organs, mainly by T lymphocytes, including those with suppressor properties, makes it necessary to conduct a differential diagnosis between the morphological manifestation of the protective cellular immune response and direct viral lesions but does not exclude the hypothesis of an immunopathological component of pathogenesis. In many of the deceased, even in the absence of clear clinical symptoms, a variety of extrapulmonary lesions were also detected. The mechanism of their development probably has a complex nature: direct lesions associated with the generalization of viral infection and vascular disorders associated with endothelial damage and having an autoimmune nature. Many aspects of the pathogenesis of coronavirus infection require further comprehensive study.<\/jats:p>","DOI":"10.3390\/pathophysiology29020021","type":"journal-article","created":{"date-parts":[[2022,6,12]],"date-time":"2022-06-12T23:55:24Z","timestamp":1655078124000},"page":"281-297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SARS-CoV-2-Induced Pathology\u2014Relevance to COVID-19 Pathophysiology"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7361-1927","authenticated-orcid":false,"given":"Vsevolod A.","family":"Zinserling","sequence":"first","affiliation":[{"name":"Department of Pathology, Institute of Experimental Medicine Almazov Research Center, Saint-Petersburg 197341, Russia"},{"name":"Center of Infectious Pathology, S.P. Botkin Infectious Hospital, Saint-Petersburg 195067, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4069-0678","authenticated-orcid":false,"given":"Natalia Yu","family":"Semenova","sequence":"additional","affiliation":[{"name":"Department of Pathology, Institute of Experimental Medicine Almazov Research Center, Saint-Petersburg 197341, Russia"},{"name":"Center of Infectious Pathology, S.P. Botkin Infectious Hospital, Saint-Petersburg 195067, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia E.","family":"Bikmurzina","sequence":"additional","affiliation":[{"name":"Department of Physiology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia M.","family":"Kruglova","sequence":"additional","affiliation":[{"name":"Department of Physiology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana V.","family":"Rybalchenko","sequence":"additional","affiliation":[{"name":"Department of Physiology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2867-044X","authenticated-orcid":false,"given":"Alexander G.","family":"Markov","sequence":"additional","affiliation":[{"name":"Department of Physiology, Saint-Petersburg State University, Saint-Petersburg 199034, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ziebuhr, J. (2016). Coronaviruses, Springer. [1st ed.].","DOI":"10.1007\/978-3-662-48678-8_58"},{"key":"ref_2","unstructured":"Dave, C. (2008). SARS- and Other Coronaviruses, Springer."},{"key":"ref_3","unstructured":"Rahul, V. (2020). MERS Coronavirus: Methods and Protocols, Springer."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1053\/j.semdp.2019.04.006","article-title":"Emerging respiratory infections: The infectious disease pathology of SARS, MERS, pandemic influenza, and Legionella","volume":"36","author":"Bradley","year":"2019","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jmii.2020.03.022","article-title":"Genotype and phenotype of COVID-19: Their roles in pathogenesis","volume":"54","author":"Mousavizadeh","year":"2021","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s00428-020-02903-8","article-title":"Post-mortem viral dynamics and tropism in COVID-19 patients in correlation with organ damage","volume":"478","author":"Skok","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1007\/s00134-020-06028-z","article-title":"Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China","volume":"46","author":"Ruan","year":"2020","journal-title":"Intensiv. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108426","DOI":"10.1016\/j.clim.2020.108426","article-title":"On the molecular determinants of the SARS-CoV-2 attack","volume":"215","author":"Kanduc","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"152072","DOI":"10.1016\/j.scitotenv.2021.152072","article-title":"CD147-spike protein interaction in CXVID-19: Get the ball rolling with a novel receptor and therapeutic target","volume":"808","author":"Behl","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/PAS.0000000000001563","article-title":"Comparison of RNA In Situ Hybridization and Immunohistochemistry Techniques for the Detection and Localization of SARS-CoV-2 in Human Tissues","volume":"45","author":"Massoth","year":"2021","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/PAI.0000000000000992","article-title":"A Standardization Protocol for the In Situ Detection of SARS-CoV2 RNA and Proteins","volume":"30","author":"Nuovo","year":"2021","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1002\/alr.22593","article-title":"Potential pathogenesis of ageusia and anosmia in COVID-19 patients","volume":"10","author":"Vaira","year":"2020","journal-title":"Int. Forum. Allergy Rhinol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Chertow, D., Stein, S., Ramelli, S., Grazioli, A., Chung, J., Singh, M., Yinda, C.K., Winkler, C., and Ylaya, J.D.K. (2021). SARS-CoV-2 infection and persistence throughout the human body and brain. Biol. Sci., Preprint.","DOI":"10.21203\/rs.3.rs-1139035\/v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1136\/jclinpath-2020-206522","article-title":"Autopsy in suspected COVID-19 cases","volume":"73","author":"Hanley","year":"2020","journal-title":"J. Clin. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0250708","DOI":"10.1371\/journal.pone.0250708","article-title":"Disturbanxes of immune responce Pathological findings in organs and tissues of patients with COVID-19: A systematic review","volume":"16","author":"Peiris","year":"2021","journal-title":"PLoS ONE"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102597","DOI":"10.1016\/j.autrev.2020.102597","article-title":"Covid-19 and autoimmunity","volume":"19","author":"Ehrenfeld","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"350","DOI":"10.7326\/M20-2566","article-title":"Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results from a Prospective, Single-Center, Clinicopathologic Case Series","volume":"173","author":"Lax","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ajpath.2020.08.009","article-title":"Immunopathology of Hyperinflammation in COVID-19","volume":"191","author":"Gustine","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/imm.13457","article-title":"The relationship between peripheral immune response and disease severity in SARS-CoV-2-infected subjects: A cross-sectional study","volume":"165","author":"Walter","year":"2022","journal-title":"Immunology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhang, J., Yang, Y., Ma, H., Li, Z., Zhang, J., Cheng, J., Zhang, X., Zhao, Y., and Xia, Z. (2020). The potential role of IL-6 in monitoring severe case of coronavirus disease 2019. medRxiv.","DOI":"10.1101\/2020.03.01.20029769"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s13054-019-2395-8","article-title":"The effect of corticosteroids on mortality of patients with influenza pneumonia: A systematic review and meta-analysis","volume":"23","author":"Ni","year":"2019","journal-title":"Crit. Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s41586-022-04421-w","article-title":"The cGAS\u2013STING pathway drives type I IFN immunopathology in COVID-19","volume":"603","author":"Gulen","year":"2022","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00428-020-02886-6","article-title":"Pulmonary pathology and COVID-19: Lessons from autopsy. The experience of European Pulmonary Pathologists","volume":"477","author":"Calabrese","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1055\/a-1191-8094","article-title":"Inflammatory Cell Infiltration of Adrenals in COVID-19","volume":"52","author":"Zinserling","year":"2020","journal-title":"Horm. Metab. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1354\/vp.42-3-321","article-title":"Morphologic Features and Development of Granulomatous Vasculitis in Feline Infectious Peritonitis","volume":"42","author":"Kipar","year":"2005","journal-title":"Vet. Pathol."}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/29\/2\/21\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:45Z","timestamp":1760138865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/29\/2\/21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["pathophysiology29020021"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology29020021","relation":{},"ISSN":["1873-149X"],"issn-type":[{"type":"electronic","value":"1873-149X"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}