ABSTRACT
Myocarditis in response to COVID-19 vaccination has been reported since early 2021. In particular, young male individuals have been identified to exhibit an increased risk of myocardial inflammation following the administration of mRNA-based vaccines. Even though the first epidemiological analyses and numerous case reports investigated potential relationships, endomyocardial biopsy (EMB)-proven cases are limited. Here, we present a comprehensive histopathological analysis of EMBs from 15 patients with reduced ejection fraction (LVEF = 30 (14-39)%) and the clinical suspicion of myocarditis following vaccination with Comirnaty® (Pfizer-BioNTech) (n = 11), Vaxzevria® (AstraZenica) (n = 2) and Janssen® (Johnson & Johnson) (n = 2). Immunohistochemical EMB analyses reveal myocardial inflammation in 14 of 15 patients, with the histopathological diagnosis of active myocarditis according the Dallas criteria (n = 2), severe giant cell myocarditis (n = 2) and inflammatory cardiomyopathy (n = 10). Importantly, infectious causes have been excluded in all patients. The SARS-CoV-2 spike protein has been detected sparsely on cardiomyocytes of nine patients, and differential analysis of inflammatory markers such as CD4+ and CD8+ T cells suggests that the inflammatory response triggered by the vaccine may be of autoimmunological origin. Although a definitive causal relationship between COVID-19 vaccination and the occurrence of myocardial inflammation cannot be demonstrated in this study, data suggest a temporal connection. The expression of SARS-CoV-2 spike protein within the heart and the dominance of CD4+ lymphocytic infiltrates indicate an autoimmunological response to the vaccination.
Subject(s)
COVID-19 , Myocarditis , Biopsy , CD8-Positive T-Lymphocytes , COVID-19 Vaccines/adverse effects , Humans , Inflammation/etiology , Male , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination/adverse effectsABSTRACT
Zusammenfassung Seit Beginn der COVID-19-Pandemie konnten zahlreiche Erkenntnisse uber den 3-phasigen Verlauf einer SARS-CoV-2-Infektion, den Infektionsweg und die Bedeutung einer vaskularen Dysfunktion gewonnen werden. Im Rahmen der Infektion kann es zu einer hyperinflammatorischen Phase mit sekundaren Organschaden bis hin zum Tod kommen. Diese schweren Krankheitsverlaufe gehen mit einer unkontrollierten Freisetzung von Entzundungsmediatoren und Zytokinen einher. Auf zellularer Ebene bedingt der membrangebundene ACE-2-Rezeptor die Invasion des Virus und stimuliert uber einen 2. Mechanismus die Metalloprotease ADAM17 sowie die Freisetzung von Zytokinen. Vasokonstriktive Veranderungen sowie die systemischen Inflammationsreaktionen fuhren zu hypoxischen Organschaden und thrombotischen Komplikationen. Die mikrovaskulare Dysfunktion, Mikroangiopathien - insbesondere der kleinen Lungengefa ss e - sowie eine Endotheliitis konnen Erklarungsansatze fur die ausgepragte systemische, mikrovaskulare Storung bei schweren Infektionen mit SARS-CoV-2 liefern. Abstract The global involvement of coronavirus disease 19 (COVID-19) provokes multiple findings about the clinical course in three phases, the infection pathway and the vascular function. Severe course of SARS-CoV-2-infection is defined as massive inflammatory reaction with elevated pro-inflammatory cytokines resulting in acute respiratory stress syndrome and the involvement of secondary organ damages with even life-threatening cardiovascular and pulmonary complications. Mechanistically, SARS-CoV-2 invades human cells with binding at angiotensin converting enzyme 2 and following another secondary pathway with ADAM17-mediated systemic release of cytokines and pro-inflammatory markers. Systemic inflammation and vasoconstriction lead to hypoxia and pro-thrombotic complications. Microvascular dysfunction, microangiopathy of small lung vessels and endotheliitis may provide new approaches for systemic inflammation due to SARS-CoV-2 infection.
Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Coronavirus Infections/virology , Myocarditis/virology , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , RNA, Messenger/genetics , Adult , Biopsy/methods , COVID-19 , Coronavirus Infections/diagnosis , Diagnosis, Differential , Humans , Male , Myocarditis/diagnosis , Pandemics , Pneumonia, Viral/diagnosis , SARS-CoV-2ABSTRACT
AIMS: Since December 2019, the novel coronavirus SARS-CoV-2 has spread rapidly throughout China and keeps the world in suspense. Cardiovascular complications with myocarditis and embolism due to COVID-19 have been reported. SARS-CoV-2 genome detection in the heart muscle has not been demonstrated so far, and the underlying pathophysiological mechanisms remain to be investigated. METHODS AND RESULTS: Endomyocardial biopsies (EMBs) of 104 patients (mean age: 57.90 ± 16.37 years; left ventricular ejection fraction: 33.7 ± 14.6%, sex: n = 79 male/25 female) with suspected myocarditis or unexplained heart failure were analysed. EMB analysis included histology, immunohistochemistry, and detection of SARS-CoV-2 genomes by real-time reverse transcription polymerase chain reaction in the IKDT Berlin, Germany. Among 104 EMBs investigated, five were confirmed with SARS-CoV-2 infected by reverse real-time transcriptase polymerase chain reaction. We describe patients of different history of symptoms and time duration. Additionally, we investigated histopathological changes in myocardial tissue showing that the inflammatory process in EMBs seemed to permeate vascular wall leading to small arterial obliteration and damage. CONCLUSIONS: This is the first report that established the evidence of SARS-CoV-2 genomes detection in EMBs. In these patients, myocardial injury ischaemia may play a role, which could explain the ubiquitous troponin increases. EMB-based identification of the cause of myocardial injury may contribute to explain the different evolution of complicated SARS-CoV-2-infection and to design future specific and personalized treatment strategies.