{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:40:13Z","timestamp":1760060413794,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>This narrative review explains the history of anaphylactic or hypersensitivity reactions, their connection to the cardiovascular system, and Kounis syndrome, which is linked to hypersensitivity. Additional subjects discussed include immunoglobulin E and serum tryptase, common pathways of allergic and nonallergic cardiovascular events, current perspectives on Kounis syndrome, allergic myocardial infarction, allergic angina, and the impact of COVID-19 and its vaccination on Kounis syndrome. Kounis syndrome is a distinct kind of acute vascular disease that affects the coronary, cerebral, mesenteric, peripheral, and venous systems. Kounis syndrome is currently used to describe coronary symptoms linked to disorders involving mast cell activation and inflammatory cell interactions, such as those involving T-lymphocytes and macrophages, which further induce allergic, hypersensitive, anaphylactic, or anaphylactic insults. Platelet activating factor, histamine, neutral proteases like tryptase and chymase, arachidonic acid products, and a range of cytokines and chemokines released during the activation process are among the inflammatory mediators that cause it. Proinflammatory cytokines are primarily produced by mast cells in COVID-19 infections. Mast cell-derived proteases and eosinophil-associated mediators are also more prevalent in the lung tissues and sera of COVID-19 patients. As a modern global threat to civilization, COVID-19 is linked to chemical patterns that can activate mast cells; therefore, allergic stimuli are usually the reason. Virus-associated molecular patterns can activate mast cells, but allergic triggers are typically the cause. By activating SARS-CoV-2 and other toll-like receptors, a variety of proinflammatory mediators, including IL-6 and IL-1\u03b2, are released, potentially contributing to the pathology of COVID-19.<\/jats:p>","DOI":"10.3390\/jcdd12090325","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T07:30:29Z","timestamp":1756107029000},"page":"325","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Acute Carditis, Rheumatic Carditis, and Morphologic Cardiac Reactions to Allergic Angina, Allergic Myocardial Infarction, and Kounis Syndrome: A Multidisciplinary and Multisystem Disease"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-6710","authenticated-orcid":false,"given":"Nicholas G.","family":"Kounis","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University Hospital of Patras, 26500 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-1859","authenticated-orcid":false,"given":"Alexandros","family":"Stefanidis","sequence":"additional","affiliation":[{"name":"First Cardiology Department, General Hospital of Nikea, Agios Panteleimon Piraeus, 3 D Mantouvalou Street, 18454 Piraeus, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-7523","authenticated-orcid":false,"given":"Ming-Yow","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, 18 No. 291, Zhongzheng Rd., Zhonghe District, New Taipei City 23561, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 110301, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-7654","authenticated-orcid":false,"given":"U\u011fur","family":"\u00d6zkan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Medicine, Trakya University, 22030 Edirne, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-266X","authenticated-orcid":false,"given":"Cesare","family":"de Gregorio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina Medical School, 98122 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0043-9051","authenticated-orcid":false,"given":"Alexandr","family":"Ceasovschih","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Second Internal Medicine Department, \u201cSf. Spiridon\u201d Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1610-0156","authenticated-orcid":false,"given":"Virginia","family":"Mplani","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Patras University Hospital, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-6954","authenticated-orcid":false,"given":"Christos","family":"Gogos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Mamatseio, General Hospital of Kozani, 50100 Kozani, Greece"},{"name":"First University Cardiology Department, AHEPA General Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-3681","authenticated-orcid":false,"given":"Stelios F.","family":"Assimakopoulos","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5449-0911","authenticated-orcid":false,"given":"Christodoulos","family":"Chatzigrigoriadis","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5514-7083","authenticated-orcid":false,"given":"Panagiotis","family":"Plotas","sequence":"additional","affiliation":[{"name":"Department of Speech Therapy, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Periklis","family":"Dousdampanis","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Saint Andrews State General Hospital, 26221 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2544-1044","authenticated-orcid":false,"given":"Sophia N.","family":"Kouni","sequence":"additional","affiliation":[{"name":"Speech Therapy Practice, Queen Olgas Square, 26221 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-0765","authenticated-orcid":false,"given":"Grigorios","family":"Tsigkas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University Hospital of Patras, 26500 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Patsouras","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University Hospital of Patras, 26500 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranco","family":"Calogiuri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Immunology and Infectious Diseases, Section of Allergology and Clinical Immunology, University of Bari Medical School, 70121 Bari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soheila","family":"Pourmasumi","sequence":"additional","affiliation":[{"name":"Clinical Research Development Unit, Ali-Ibn Abi-Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan 7717933777, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioanna","family":"Koniari","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University Hospital of Patras, 26500 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1111\/j.1398-9995.2004.00603.x","article-title":"Pharaoh Menes\u2019 death after an anaphylactic reaction the end of a myth","volume":"59","author":"Krombach","year":"2004","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1001\/jama.1938.62790140001008","article-title":"Serum carditis: Morphologic cardiac alterations in man with serum disease","volume":"110","author":"Clark","year":"1938","journal-title":"J. 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