Evidence of SARS-CoV-2 mRNA in endomyocardial biopsies of patients with clinically suspected myocarditis tested negative for COVID-19 in nasopharyngeal swab.
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ABSTRACT:
SUBMITTER: Wenzel P
PROVIDER: S-EPMC7337685 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Evidence of SARS-CoV-2 mRNA in endomyocardial biopsies of patients with clinically suspected myocarditis tested negative for COVID-19 in nasopharyngeal swab.
Wenzel Philip P Kopp Sabrina S Göbel Sebastian S Jansen Thomas T Geyer Martin M Hahn Felix F Kreitner Karl-Friedrich KF Escher Felicitas F Schultheiss Heinz-Peter HP Münzel Thomas T
Cardiovascular research 20200801 10
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Project description:AimsMyocardial inflammation is increasingly detected noninvasively by tissue mapping with cardiovascular magnetic resonance (CMR). Intraindividual agreement with endomyocardial biopsy (EMB) or markers of myocardial injury, high-sensitive cardiac troponin (hs-cTnT) in patients with clinically suspected viral myocarditis is incompletely understood.MethodsProspective multicenter study of consecutive patients with clinically suspected myocarditis who underwent blood testing for hs-cTnT, CMR, and EMB as a part of diagnostic workup. EMB was considered positive based on immunohistological criteria in line with the European Society of Cardiology (ESC) definitions. CMR diagnoses employed tissue mapping using sequence-specific cut-off for native T1 and T2 mapping; active inflammation was defined as T1 ≥2 standard deviation (SD) and T2 ≥2 SD above the mean of normal range. Hs-cTnT of greater than 13.9 ng/L was considered significant.ResultsA total of 114 patients (age (mean ± SD) 54 ± 16, 65% males) were included, of which 79 (69%) had positive EMB criteria, 64 (56%) CMR criteria, and a total of 58 (51%) positive troponin. Agreement between EMB and CMR diagnostic criteria was poor (CMR vs ESC: area under the curve (AUC): 0.51 (0.39-0.62)). The agreement between a significant hs-cTnT rise and CMR-based diagnosis of myocarditis was good (AUC: 0.84 (0.68-0.92); p < 0.001), but poor for EMB (0.50 (0.40-0.61). Hs-cTnT was significantly associated with native T1 and T2, high-sensitive C-reactive protein, and N-terminal pro-hormone brain natriuretic peptide (r = 0.37, r = 0.35, r = 0.30, r = 0.25; p < 0.001), but not immunohistochemical criteria or viral presence.ConclusionIn clinically suspected viral myocarditis, all diagnostic approaches reflect the pathophysiological elements of myocardial inflammation; however, the differing underlying drivers only partially overlap. The EMB and CMR diagnostic algorithms are neither interchangeable in terms of interpretation of myocardial inflammation nor in their relationship with myocardial injury.
| S-EPMC11565394 | biostudies-literature
Project description:BackgroundEndomyocardial biopsy (EMB) is currently considered the gold standard for diagnosing cardiac allograft rejection. However, significant limitations related to histological interpretation variability are well-recognized. We sought to develop a methodology to evaluate EMB solely based on gene expression, without relying on histology interpretation.MethodsSixty-four EMBs were obtained from 47 post-heart transplant recipients, who were evaluated for allograft rejection. EMBs were subjected to mRNA sequencing, in which an unsupervised classification algorithm was used to identify the molecular signatures that best classified the EMBs. Cytokine and natriuretic peptide peripheral blood profiling was also performed. Subsequently, we performed gene network analysis to identify the gene modules and gene ontology to understand their biological relevance. We correlated our findings with the unsupervised and histological classifications.ResultsOur algorithm classifies EMBs into three categories based solely on clusters of gene expression: unsupervised classes 1, 2, and 3. Unsupervised and histological classifications were closely related, with stronger gene module-phenotype correlations for the unsupervised classes. Gene ontology enrichment analysis revealed processes impacting on the regulation of cardiac and mitochondrial function, immune response, and tissue injury response. Significant levels of cytokines and natriuretic peptides were detected following the unsupervised classification.ConclusionWe have developed an unsupervised algorithm that classifies EMBs into three distinct categories, without relying on histology interpretation. These categories were highly correlated with mitochondrial, immune, and tissue injury response. Significant cytokine and natriuretic peptide levels were detected within the unsupervised classification. If further validated, the unsupervised classification could offer a more objective EMB evaluation.
| S-EPMC10524567 | biostudies-literature
Project description:This case study aimed to identify rare viral myocarditis combined with encephalitis as a COVID-19 vaccine complication. A 59-year-old male patient with a 2 day history of headache and rapidly progressive cognitive decline, who had received the third dose of COVID-19 vaccine 12 days before, was admitted to our hospital. The patient had no underlying systemic conditions, no prior medical history, and no prior history of COVID-19 infection. The patient was diagnosed with viral myocarditis and encephalitis by two neurologists and two cardiologists after laboratory examination, head computed tomography, and magnetic resonance imaging evaluation. The patient experienced cardiogenic shock and developed severe arrhythmia, resulting in his death 10 h after admission. Clinically suspected lethal viral myocarditis combined with encephalitis in the patient could be related to COVID-19 vaccination. Adverse effects of the Chinese COVID-19 vaccine, especially serious complications, have been uncommon. This case study highlights a rare complication after COVID-19 vaccination that needs high attention.
| S-EPMC9877651 | biostudies-literature
Project description:COVID-19 diagnosis relies on molecular testing for SARS-CoV-2 via nasopharyngeal swab in the presence of suggestive clinical, radiological and laboratory findings. Since bronchoalveolar lavage liquid (BAL) collected during fibrobronchoscopy may increase test sensitivity compared to nasopharyngeal swabs, it was performed during the 2020 pandemic in clinically or radiologically suspected cases. Our aim was to determine whether clinical features, chest computed tomography (CT) findings or laboratory tests may predict patients testing positive for SARS-CoV-2 at BAL after a negative nasopharyngeal swab. We performed a retrospective cross-sectional study with multivariable analysis of suspected patients who were tested for SARS-CoV-2 at BAL after at least one negative nasopharyngeal swab. Univariable logistic regression for odds ratio and multivariate models was calculated to determine clinical, radiological and laboratory predictors. 32/198 (16%) patients had BAL positive for SARS-CoV-2, while 65/198 tested positive for other pathogens at BAL. Of the 32 patients positive for COVID, 4 had a coinfection at BAL, being thus positive both for COVID as well as for another pathogen while the remaining 105 patients were negative for COVID and other pathogens at BAL. COVID-19 patients had more often highly suggestive CT findings, higher number of involved lobes, more often ground glass opacity of more than 50% of lung parenchyma, and less frequently other radiologically suspected infections. At multivariate model, temperature also predicted BAL positivity. The procedure was well tolerated-with only one desaturation episode-while no healthcare worker was infected. In conclusion, when nasopharyngeal swabs are negative but there is clinical or imaging suspicion of COVID-19, BAL represents a complementary diagnostic tool, particularly in conjunction with suggestive/more extensive lung involvement at CT scan. The procedure did not carry increased risks for patients nor for operators, while allowing to free hospital resources, avoiding unnecessary isolations.
| S-EPMC7994348 | biostudies-literature
Project description:ObjectivesThe aim of this study was to describe the method used to perform electrogram-guided EMB and correlate electrogram characteristics with pathological and clinical outcomes.BackgroundEndomyocardial biopsy (EMB) is valuable in determining the underlying etiology of a cardiomyopathy. The sensitivity, however, for focal disorders, such as lymphocytic myocarditis and cardiac sarcoidosis (CS), is low. The sensitivity of routine fluoroscopically guided EMB is low. Abnormal intracardiac electrograms are seen at sites of myocardial disease. However, the exact value of electrogram-guided EMB is unknown.MethodsWe report 11 patients who underwent electrogram-guided EMB for evaluation of myocarditis and CS.ResultsOf 40 total biopsy specimens taken from 11 patients, 19 had electrogram voltage <5 mV, all of which resulted in histopathologic abnormality (100% specificity and positive predictive value). A voltage amplitude cutoff value of 5 mV had substantially higher sensitivity (70% vs. 26%) and negative predictive value (62%) than 1.5 mV. Abnormal electrogram appearance at biopsy site had good sensitivity (67%) and specificity (92%) in predicting abnormal myocardium. Normal signals with voltage >5 mV signified normal myocardium with no significant diagnostic yield. Biopsy results guided therapy in all patients, including 5 with active myocarditis or CS, all of whom subsequently received immunosuppressive therapy. There were no procedural complications.ConclusionsIn patients with suspected myocarditis or CS, electrogram-guided EMB targeting sites with abnormal or low-amplitude electrograms may increase the diagnostic yield for detecting abnormal pathological findings.
| S-EPMC4459501 | biostudies-literature
Project description:The present study evaluated the role of SNP microarray in 101 cases of clinically suspected FISH negative (noninformative/normal) 22q11.2 microdeletion syndrome. SNP microarray was carried out using 300 K HumanCytoSNP-12 BeadChip array or CytoScan 750 K array. SNP microarray identified 8 cases of 22q11.2 microdeletions and/or microduplications in addition to cases of chromosomal abnormalities and other pathogenic/likely pathogenic CNVs. Clinically suspected specific deletions (22q11.2) were detectable in approximately 8% of cases by SNP microarray, mostly from FISH noninformative cases. This study also identified several LOH/AOH loci with known and well-defined UPD (uniparental disomy) disorders. In conclusion, this study suggests more strict clinical criteria for FISH analysis. However, if clinical criteria are few or doubtful, in particular newborn/neonate in intensive care, SNP microarray should be the first screening test to be ordered. FISH is ideal test for detecting mosaicism, screening family members, and prenatal diagnosis in proven families.
| S-EPMC4804090 | biostudies-literature
Project description: Not available
| S-EPMC10364491 | biostudies-literature
Project description:BackgroundThe aim of this study was to investigate the clinical significance of Quilty lesions in endomyocardial biopsies (EMBs) of cardiac transplantation patients.MethodsA total of 1190EMBs from 117 cardiac transplantation patients were evaluated histologically for Quilty lesions,acute cellular rejection, and antibody-mediated rejection. Cardiac allograft vasculopathy wasdiagnosed by computed tomography coronary angiography. Clinical information, including thepatients' survival was retrieved by a review of medical records.ResultsEighty-eight patients(75.2%) were diagnosed with Quilty lesions, which were significantly associated with acute cellularrejection, but not with acute cellular rejection ≥ 2R or antibody-mediated rejection. In patientsdiagnosed with both Quilty lesions and acute cellular rejection, the time-to-onset of Quilty lesionsfrom transplantation was longer than that of acute cellular rejections. We found a significant associationbetween Quilty lesions and cardiac allograft vasculopathy. No significant relationship wasfound between Quilty lesions and the patients' survival.ConclusionsQuilty lesion may be an indicator of previous acute cellular rejection rather than a predictor for future acute cellular rejection.
| S-EPMC6344801 | biostudies-literature
Project description:Our goals were to determine whether (i) gene expression patterns in biopsies grouped by acute rejection grade (AR) would be consistent; (ii) a characteristic gene expression profile would be associated with ISHLT Grade 0, 1A & 1B (equivalent to 1R on recently revised criteria) and ISHLT grade 3A & 3B (equivalent to 2R & 3R on recently revised criteria); (iii) gene expression patterns emerging from the analysis would provide insights into mechanisms of AR. The samples used for gene expression profiling were endomyocardial biopsies (EMB) with different acute rejection gradings. The EMB (n=2726) were obtained from the right site of the interventricular septum of heart transplant recipients (n=2423) and graded according to the guidelines of the International Society for Heart and Lung Transplantation (ISHLT, grade 0, n=9; grade1A, n=5; 1B, n=5; 3A, n=4; 3B, n=43). Selection criteria for inclusion of patients in this analysis required the availability of appropriately stored EMB samples for RNA extraction; absence of any infection that required treatment with an antimicrobial drug at anytime during the posttransplant course of the patient; absence of prior AR rejection of any grade; absence of hemodynamic compromise at the time of EMB; use of standard immunosuppressive regimen; and the absence of HLA antibodies prior to transplant.
2008-10-18 | GSE9377 | GEO
Project description:BackgroundMapping techniques using cardiac magnetic resonance imaging have significantly improved the diagnostic accuracy for myocarditis with focal myocardial injuries. The aim of our study was to determine whether T1 and T2 mapping techniques could identify diffuse myocardial injuries in "normal-appearing" myocardium in pediatric patients with clinically suspected myocarditis and to evaluate the associations between diffuse myocardial injuries and cardiac function parameters.MethodsForty-six subjects were included in this study: 20 acute myocarditis patients, 11 subacute/chronic myocarditis patients and 15 control children. T2 values, native T1 values and the extracellular volume (ECV) of "normal-appearing" myocardium were compared among the three groups of patients. Associations between diffuse myocardial injuries and cardiac function parameters were also evaluated.ResultsThe ECV of "normal-appearing" myocardium was significantly higher in the subacute/chronic myocarditis group than in the control group (30.1 ± 0.9 vs 27.0 ± 0.6, P =0.004). No significant differences in T1 and T2 values between the acute myocarditis and control groups were found. In the subacute/chronic myocarditis group, a significant association between ECV and left ventricle ejection fraction was found (P=0.03).ConclusionsDiffuse myocardial injuries are likely to occur in subacute/chronic myocarditis patients with prolonged inflammatory responses. Mapping techniques have great value for the diagnosis and monitoring of myocarditis.
| S-EPMC7648451 | biostudies-literature