{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T03:22:13Z","timestamp":1774408933536,"version":"3.50.1"},"reference-count":81,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Health Ministry","award":["NET-2016\u201302363853"],"award-info":[{"award-number":["NET-2016\u201302363853"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A complete understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) physiopathology and related histopathologic lesions is necessary to improve treatment and outcome of coronavirus disease 2019 (COVID-19) patients. Many studies have focused on autopsy findings in COVID-19-related deaths to try and define any possible specific pattern. Histopathologic alterations are principally found within lungs and blood vessels, and these abnormalities also seem to have the highest clinical impact. Nevertheless, many of the morphological data collected so far are non-specific, fickle, and possibly associated with other co-existing factors. The aim of this minireview is to describe the main histopathological features related to COVID-19 and the mechanism known as \u201ccytokine storm\u201d.<\/jats:p>","DOI":"10.3390\/ijms22020974","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T11:39:55Z","timestamp":1611056395000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The Immunopathological and Histological Landscape of COVID-19-Mediated Lung Injury"],"prefix":"10.3390","volume":"22","author":[{"given":"Giovanni","family":"Zarrilli","sequence":"first","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Angerilli","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Businello","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Sbaraglia","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Traverso","sequence":"additional","affiliation":[{"name":"Istituto Oncologico Veneto, IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8954-5888","authenticated-orcid":false,"given":"Francesco","family":"Fortarezza","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9528-4883","authenticated-orcid":false,"given":"Monica","family":"De Gaspari","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0195-9753","authenticated-orcid":false,"given":"Cristina","family":"Basso","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorella","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Dei Tos","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-5482","authenticated-orcid":false,"given":"Matteo","family":"Fassan","sequence":"additional","affiliation":[{"name":"Department of Medicine (DIMED), Surgical Pathology &amp; Cytopathology Unit, University of Padua, 35121 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bogoch, I.I., Watts, A., Thomas-Bachli, A., Huber, C., Kraemer, M.U.G., and Khan, K. (2020). Pneumonia of unknown aetiology in Wuhan, China: Potential for international spread via commercial air travel. J. Travel Med., 27.","DOI":"10.1093\/jtm\/taaa008"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/tmi.13383","article-title":"The COVID-19 epidemic","volume":"25","author":"Velavan","year":"2020","journal-title":"Trop. Med. Int. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1146\/annurev-virology-110615-042301","article-title":"Structure, Function, and Evolution of Coronavirus Spike Proteins","volume":"3","author":"Li","year":"2016","journal-title":"Annu Rev. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41422-020-0327-4","article-title":"COVID-19: Towards understanding of pathogenesis","volume":"30","author":"Cao","year":"2020","journal-title":"Cell Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/s41591-020-0968-3","article-title":"Extrapulmonary manifestations of COVID-19","volume":"26","author":"Gupta","year":"2020","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s00428-020-02861-1","article-title":"Feasibility of postmortem examination in the era of COVID-19 pandemic: The experience of a Northeast Italy University Hospital","volume":"477","author":"Basso","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"153097","DOI":"10.1016\/j.prp.2020.153097","article-title":"Pathologic features of COVID-19: A concise review","volume":"216","author":"Tabary","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1093\/infdis\/jiaa578","article-title":"Postmortem Findings in Italian Patients With COVID-19: A Descriptive Full Autopsy Study of Cases With and Without Comorbidities","volume":"222","author":"Falasca","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.chest.2020.03.060","article-title":"A Call to Action: The Need for Autopsies to Determine the Full Extent of Organ Involvement Associated With COVID-19","volume":"158","author":"Barth","year":"2020","journal-title":"Chest"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1038\/s41379-020-00661-1","article-title":"COVID-19 pulmonary pathology: A multi-institutional autopsy cohort from Italy and New York City","volume":"33","author":"Borczuk","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13000-020-01017-8","article-title":"Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)\u2014anatomic pathology perspective on current knowledge","volume":"15","author":"Mohanty","year":"2020","journal-title":"Diagn. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M20-2003","article-title":"Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study","volume":"173","author":"Wichmann","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhou, B., Zhao, W., Feng, R., Zhang, X., Li, X., Zhou, Y., Peng, L., Li, Y., Zhang, J., and Luo, J. (2020). The pathological autopsy of coronavirus disease 2019 (COVID-2019) in China: A review. Pathog. Dis., 78.","DOI":"10.1093\/femspd\/ftaa026"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1093\/ajcp\/aqaa062","article-title":"COVID-19 Autopsies, Oklahoma, USA","volume":"153","author":"Barton","year":"2020","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2157","DOI":"10.3201\/eid2609.201353","article-title":"Clinicopathologic and Immunohistochemical Findings from Autopsy of Patient with COVID-19, Japan","volume":"26","author":"Adachi","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S2213-2600(20)30243-5","article-title":"Pulmonary and cardiac pathology in African American patients with COVID-19: An autopsy series from New Orleans","volume":"8","author":"Fox","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"107233","DOI":"10.1016\/j.carpath.2020.107233","article-title":"The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): Report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities","volume":"48","author":"Buja","year":"2020","journal-title":"Cardiovasc. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1136\/jclinpath-2020-206710","article-title":"COVID-19 autopsy in people who died in community settings: The first series","volume":"73","author":"Youd","year":"2020","journal-title":"J. Clin. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/his.14134","article-title":"Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction","volume":"77","author":"Menter","year":"2020","journal-title":"Histopathology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1007\/s00414-020-02317-w","article-title":"Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany","volume":"134","author":"Edler","year":"2020","journal-title":"Int. J. Legal Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/S0140-6736(20)31305-2","article-title":"Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: A case series","volume":"396","author":"Bradley","year":"2020","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Deshmukh, V., Motwani, R., Kumar, A., Kumari, C., and Raza, K. (2020). Histopathological observations in COVID-19: A systematic review. J. Clin Pathol.","DOI":"10.1136\/jclinpath-2020-206995"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/s41379-020-0536-x","article-title":"Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies","volume":"33","author":"Tian","year":"2020","journal-title":"Mod. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Elsoukkary, S.S., Mostyka, M., Dillard, A., Berman, D.R., Ma, L.X., Chadburn, A., Yantiss, R.K., Jessurun, J., Seshan, S.V., and Borczuk, A.C. (2020). Autopsy Findings in 32 Patients with COVID-19: A Single-Institution Experience. Pathobiology, 1\u201313.","DOI":"10.1159\/000511325"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e245","DOI":"10.1016\/S2666-5247(20)30115-4","article-title":"Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: A post-mortem study","volume":"1","author":"Hanley","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/PAF.0000000000000567","article-title":"COVID-19: Postmortem Diagnostic and Biosafety Considerations","volume":"41","author":"Lacy","year":"2020","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106239","DOI":"10.1016\/j.rmed.2020.106239","article-title":"Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians","volume":"176","author":"Batah","year":"2020","journal-title":"Respir. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1001\/jama.2020.8907","article-title":"Postmortem Examination of Patients with COVID-19","volume":"323","author":"Schaller","year":"2020","journal-title":"JAMA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1093\/ajcp\/aqaa156","article-title":"Forty Postmortem Examinations in COVID-19 Patients","volume":"154","author":"Sun","year":"2020","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"153222","DOI":"10.1016\/j.prp.2020.153222","article-title":"COVID-2019\u2014A comprehensive pathology insight","volume":"216","author":"Shanmugam","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1007\/s00134-020-06057-8","article-title":"Time to consider histologic pattern of lung injury to treat critically ill patients with COVID-19 infection","volume":"46","author":"Copin","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_34","first-page":"1","article-title":"Pneumolysis and \u201cSilent Hypoxemia\u201d in COVID-19","volume":"9","year":"2020","journal-title":"Ind. J. Clin. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.euf.2020.05.009","article-title":"Pathological Findings in the Testes of COVID-19 Patients: Clinical Implications","volume":"6","author":"Yang","year":"2020","journal-title":"Eur. Urol. Focus"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial cell infection and endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1681\/ASN.2020050744","article-title":"Postmortem Kidney Pathology Findings in Patients with COVID-19","volume":"31","author":"Santoriello","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1681\/ASN.2020060802","article-title":"Kidney Biopsy Findings in Patients with COVID-19","volume":"31","author":"Kudose","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.kint.2020.04.003","article-title":"Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China","volume":"98","author":"Su","year":"2020","journal-title":"Kidney Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1093\/eurheartj\/ehaa664","article-title":"Pathological features of COVID-19-associated myocardial injury: A multicentre cardiovascular pathology study","volume":"41","author":"Basso","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-020-02166-2","article-title":"Neuropathology of COVID-19: A spectrum of vascular and acute disseminated encephalomyelitis (ADEM)-like pathology","volume":"140","author":"Reichard","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMc2019373","article-title":"Neuropathological Features of Covid-19","volume":"383","author":"Solomon","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1053\/j.gastro.2020.02.055","article-title":"Evidence for Gastrointestinal Infection of SARS-CoV-2","volume":"158","author":"Xiao","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"473","DOI":"10.15403\/jgld-2747","article-title":"SARS-CoV-2 and hepatitis","volume":"29","author":"Trevenzoli","year":"2020","journal-title":"J. Gastrointestin. Liver Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1016\/j.jaad.2020.04.094","article-title":"Cutaneous manifestations in COVID-19: Lessons learned from current evidence","volume":"83","author":"Suchonwanit","year":"2020","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1111\/jdv.16682","article-title":"A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: Lights and shadows on the relationship with COVID-19 infection","volume":"34","author":"Diociaiuti","year":"2020","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"adv00124","DOI":"10.2340\/00015555-3490","article-title":"Cutaneous Clinico-Pathological Findings in three COVID-19-Positive Patients Observed in the Metropolitan Area of Milan, Italy","volume":"100","author":"Gianotti","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cytogfr.2020.05.003","article-title":"The cytokine storm in COVID-19: An overview of the involvement of the chemokine\/chemokine-receptor system","volume":"53","author":"Coperchini","year":"2020","journal-title":"Cytokine Growth Fact. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.3389\/fimmu.2020.01708","article-title":"Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies","volume":"11","author":"Tang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"155151","DOI":"10.1016\/j.cyto.2020.155151","article-title":"COVID-19 cytokine storm: The anger of inflammation","volume":"133","author":"Mahmudpour","year":"2020","journal-title":"Cytokine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.3389\/fimmu.2020.01446","article-title":"The COVID-19 Cytokine Storm; What We Know So Far","volume":"11","author":"Ragab","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1001\/jamainternmed.2020.3313","article-title":"Is a \u201cCytokine Storm\u201d Relevant to COVID-19?","volume":"180","author":"Sinha","year":"2020","journal-title":"JAMA Intern. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and immunological features of severe and moderate coronavirus disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_55","first-page":"203","article-title":"Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia","volume":"43","author":"Chen","year":"2020","journal-title":"Zhonghua Jie He He Hu Xi Za Zhi"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/imm.13223","article-title":"Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou, China","volume":"160","author":"Tan","year":"2020","journal-title":"Immunology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e13429","DOI":"10.1111\/eci.13429","article-title":"Deciphering the COVID-19 cytokine storm: Systematic review and meta-analysis","volume":"51","author":"Mulchandani","year":"2021","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.immuni.2020.04.003","article-title":"COVID-19: A New Virus, but a Familiar Receptor and Cytokine Release Syndrome","volume":"52","author":"Hirano","year":"2020","journal-title":"Immunity"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Hu, B., Huang, S., and Yin, L. (2020). The cytokine storm and COVID-19. J. Med. Virol.","DOI":"10.1002\/jmv.26232"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Pelaia, C., Tinello, C., Vatrella, A., De Sarro, G., and Pelaia, G. (2020). Lung under attack by COVID-19-induced cytokine storm: Pathogenic mechanisms and therapeutic implications. Ther. Adv. Respir. Dis., 14.","DOI":"10.1177\/1753466620933508"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"345","DOI":"10.5858\/arpa.2015-0519-RA","article-title":"Acute Lung Injury: A Clinical and Molecular Review","volume":"140","author":"Butt","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","article-title":"Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology","volume":"39","author":"Channappanavar","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/nsr\/nwaa041","article-title":"Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients","volume":"7","author":"Zhou","year":"2020","journal-title":"Nat. Sci. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1164\/rccm.200407-857OC","article-title":"Characterization of cytokine\/chemokine profiles of severe acute respiratory syndrome","volume":"171","author":"Jiang","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.3389\/fimmu.2020.01626","article-title":"Overview: Systemic Inflammatory Response Derived from Lung Injury Caused by SARS-CoV-2 Infection Explains Severe Outcomes in COVID-19","volume":"11","author":"Polidoro","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1111\/jth.14975","article-title":"Coagulopathy in COVID-19","volume":"18","author":"Iba","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7527953","DOI":"10.1155\/2020\/7527953","article-title":"Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment","volume":"2020","author":"Cicco","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"110102","DOI":"10.1016\/j.mehy.2020.110102","article-title":"SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression","volume":"143","author":"Cecchini","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s41232-020-00146-3","article-title":"How COVID-19 induces cytokine storm with high mortality","volume":"40","author":"Hojyo","year":"2020","journal-title":"Inflamm. Regen."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Hariharan, A., Hakeem, A.R., Radhakrishnan, S., Reddy, M.S., and Rela, M. (2020). The Role and Therapeutic Potential of NF-kappa-B Pathway in Severe COVID-19 Patients. Inflammopharmacology.","DOI":"10.1007\/s10787-020-00773-9"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1146\/annurev-biophys-083012-130338","article-title":"Molecular basis of NF-\u03baB signaling","volume":"42","author":"Napetschnig","year":"2013","journal-title":"Annu. Rev. Biophys."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fimmu.2011.00022","article-title":"A four-step model for the IL-6 amplifier, a regulator of chronic inflammations in tissue-specific MHC class II-associated autoimmune diseases","volume":"2","author":"Murakami","year":"2011","journal-title":"Front. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.4049\/jimmunol.1103613","article-title":"IL-6 amplifier, NF-\u03baB-triggered positive feedback for IL-6 signaling, in grafts is involved in allogeneic rejection responses","volume":"189","author":"Lee","year":"2012","journal-title":"J. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1093\/intimm\/dxs158","article-title":"IL-6 amplifier activation in epithelial regions of bronchi after allogeneic lung transplantation","volume":"25","author":"Lee","year":"2013","journal-title":"Int. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ingraham, N.E., Barakat, A.G., Reilkoff, R., Bezdicek, T., Schacker, T., Chipman, J.G., Tignanelli, C.J., and Puskarich, M.A. (2020). Understanding the renin-angiotensin-aldosterone-SARS-CoV axis: A comprehensive review. Eur. Respir. J., 56.","DOI":"10.1183\/13993003.00912-2020"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"L1025","DOI":"10.1152\/ajplung.00119.2020","article-title":"COVID-19: Is the ACE2 just a foe?","volume":"318","author":"Jakovac","year":"2020","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Malapelle, U., Pisapia, P., Iaccarino, A., Barberis, M., Bellevicine, C., Brunnstr\u00f6m, H., De Biase, D., De Maglio, G., Lindquist, K.E., and Fassan, M. (2020). Predictive molecular pathology in the time of coronavirus disease (COVID-19) in Europe. J. Clin. Pathol., In Press.","DOI":"10.1136\/jclinpath-2020-206957"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:13:02Z","timestamp":1760159582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,19]]},"references-count":81,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22020974"],"URL":"https:\/\/doi.org\/10.3390\/ijms22020974","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,19]]}}}