Genome-wide association study of BNT162b2 vaccine-related myocarditis identifies potential predisposing functional areas in Hong Kong adolescents.

Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field.

IL-1RA autoantibodies: insights into mechanisms and associated diseases.

The association of neutralizing autoantibodies targeting interleukin-1 receptor antagonist (IL-1RA) with multisystem inflammatory syndrome, IgG4-related disease, and vaccine-related myocarditis is increasingly recognized. The detection of IL-1RA autoantibodies can be notably affected by the techniques and methods employed. Two categories of assays are available: solid-phase immunoassays, which detect binding of IL-1RA autoantibodies, and functional IL-1 signaling reporter cell assays, which offer greater specificity by determining whether circulating autoantibodies can impede interleukin (IL)-1ß signal transduction pathways. It is as yet unclear why only a minority of individuals produce pathogenic anti-IL-1RA autoantibodies in response to coronavirus disease 2019 (COVID19) or vaccination. This review article discusses our current knowledge of the process of IL-1RA autoantibody generation, the underlying pathogenesis, detection, and potential treatment strategies for associated diseases.

Soluble factors in COVID-19 mRNA vaccine-induced myocarditis causes cardiomyoblast hypertrophy and cell injury: a case report.

BACKGROUND: Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood. CASE PRESENTATION: After the first dose, we reported an mRNA vaccine-induced perimyocarditis in a young patient with a history of recurrent myocardial inflammation episodes and progressive loss of cardiac performance. We tested this possible inflammatory cytokine-mediated cardiotoxicity after vaccination in the acute phase (ten days), and we found a significant elevation of MCP-1, IL-18, and IL-8 inflammatory mediators. Still, these cytokines decreased considerably at the recovery phase (42 days later). We used the cardiomyoblasts cell line to test the effect of serum on cell viability, observing that serum from the acute phase reduced the cell viability to 75%. We did not detect this toxicity in cells when we tested serum from the patient in the recovery phase. We also tested serum-induced hypertrophy, a phenomenon in myocarditis and heart failure. We found that acute phase-serum has hypertrophy effects, increasing 25% of the treated cardiac cells' surface and significantly increasing B-type natriuretic peptide. However, we did not observe the hypertrophic effect in the recovery phase or sera from healthy controls. CONCLUSION: Our results opened the possibility of the inflammatory cytokines or serum soluble mediators as key factors for vaccine-associated myocarditis. In this regard, identifying anti-inflammatory molecules that reduce inflammatory cytokines could help avoid vaccine-induced myocardial inflammation.

Anesthetic Management of Suspected COVID-19 Vaccination Pericarditis/Myocarditis Scheduled for a Pericardial Window: A Case Report and Literature Review.

The unique challenges posed by the COVID vaccination continue to affect multiple healthcare specialties. Although short-term studies have shown that COVID-19 vaccines are both safe and effective, reports of side effects continue to emerge. Cardiovascular side effects such as myo-pericardial inflammation are of particular interest to the fields of cardiology, anesthesiology, and surgery. Myocarditis and pericarditis necessitate diagnostic and therapeutic procedures such as transesophageal echocardiography (TEE) and pericardial window surgery. Intraoperative monitoring of clinical status and heart rhythm and careful adjustments to anesthetic management are required to ensure successful outcomes. This case report follows a 50-year-old male with a known history of pericardial effusion post-COVID vaccination who presented to the emergency department with shortness of breath and chest pain, necessitating further management. We examine the importance of TEE in preventing unnecessary pericardial window procedures and shed light on the importance of careful patient monitoring and management in promoting successful outcomes from an anesthesiology perspective.

Myocarditis associated with COVID-19 and its vaccines - a systematic review.

Since the beginning of the COVID-19 (Coronavirus Disease of 2019) pandemic, myocarditis has received much attention and controversy as one of the more worrisome cardiovascular complications. After the availability of highly effective COVID-19 mRNA vaccines in late 2020, myocarditis was also appreciated as an important vaccine-related adverse event. Though the overall frequency of clinically evident viral myocarditis is rare in the general population, young males show a higher predilection for COVID vaccine-induced myocarditis. The severity of COVID-19 viral myocarditis is variable, ranging from very mild to severe, while vaccine-induced myocarditis is usually mild, and rarely a severe or fatal disease. The diagnosis of either COVID-19 or vaccine-induced myocarditis is based on typical clinical features, laboratory investigations, and imaging, preferably with cardiac magnetic resonance. The management of COVID-19 myocarditis is supportive care for mild or moderate disease. For the rare patient who develops severe disease, advanced heart failure therapies such as mechanical circulatory support devices may have to be employed and can be lifesaving. Avoidance of strenuous exercise during the bout of myocarditis and its recovery phase is important. Despite the small but finite risk of vaccine-induced myocarditis, the benefits of protection against COVID-19 disease and its attendant complications far outweigh the risks.

A Case Series and Literature Review of the Association of COVID-19 Vaccination With Autoimmune Diseases: Causality or Chance?

The coronavirus disease 2019 (COVID-19) pandemic has been a challenging time for the whole world. Ever since the start of the pandemic, vaccine development has been underway and now there are several approved COVID-19 vaccines bringing hope for the end of the pandemic. However, there have been been a few individuals who have been affected in some other ways by the COVID-19 vaccinations. Here in this case series, we present 16 cases of autoimmune diseases with a strong temporal relation with the COVID-19 vaccine. We would like to emphasize that COVID-19 vaccines are essential to alter the course of the pandemic and save lives and the temporal relation is not by any means proof of causation. However, we must be vigilant for the occurrence of these conditions.

COVID-19 Vaccine-Induced Myocarditis: A Systemic Review and Literature Search.

Myocarditis is one of the complications reported with COVID-19 vaccines, particularly both Pfizer-BioNTech and Moderna vaccines. Most of the published data about this association come from case reports and series. Integrating the geographical data, clinical manifestations, and outcomes is therefore important in patients with myocarditis to better understand the disease. A thorough literature search was conducted in Cochrane library, PubMed, ScienceDirect, and Google Scholar for published literature till 30 March 2022. We identified 26 patients eligible from 29 studies; the data were pooled from these qualifying case reports and case series. Around 94% of patients were male in this study, the median age for onset of myocarditis was 22 years and 85% developed symptoms after the second dose. The median time of admission for patients to hospitals post-vaccination was three days and chest pain was the most common presenting symptom in these patients. Most patients had elevated troponin on admission and about 90% of patients had cardiac magnetic resonance imaging (CMR) that showed late gadolinium enhancement. All patients admitted with myocarditis were discharged home after a median stay of four days. Results from this current analysis show that post-mRNA vaccination myocarditis is mainly seen in young males after the second dose of vaccination. The pathophysiology of vaccine-induced myocarditis is not entirely clear and late gadolinium enhancement is a common finding on CMR in these patients that may indicate myocardial fibrosis or necrosis. Prognosis remains good and all patients recovered from myocarditis, however further studies are advisable to assess long-term prognosis of myocarditis.

Clinical characteristics and prognostic factors of myocarditis associated with the mRNA COVID-19 vaccine.

To analyze the clinical presentation and outcomes of myocarditis after administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccine. Nine case series and 15 case reports (74 patients) of myocarditis after administration of the BNT162b2 or mRNA-1273 vaccine were reviewed from PubMed, Scopus, Embase, and Web of Science. We analyzed clinical manifestations, diagnostic findings, and outcomes. In addition, we performed a pooled analysis and investigated risk factors leading to admission to the intensive care unit and recovery with conservative care. Most patients were male (94.6%), and the median age (range) was 17.6 (14-70) years. Patients who received the BNT162b2 (n = 58, 78.4%) vaccine presented fewer systemic symptoms and left ventricular dysfunction than mRNA-1273 recipients. Although patients under 20 years experienced more fever and myalgia, they had better ejection fraction and less prominent myocardial inflammation in magnetic resonance imaging than older patients. The clinical course of all patients was favorable without mortality, and one-third of patients resolved with conservative care alone. Risk factor analyses revealed that patients with gastrointestinal symptoms required intensive care (odds ratio: 20.3, 95% confidence interval 1.90-217, p = 0.013). The risk of fatality in myocarditis subjected to mRNA vaccination seems to be low. However, patients with gastrointestinal symptoms received more intensive care, and a significant proportion of patients recovered with conservative management.

COVID-19 Vaccination-Associated Myocarditis: A Literature Review.

Myocarditis is defined as a non-ischemic inflammation of the middle layer of the heart. It ensues changes that can lead to acute heart failure, dilated cardiomyopathy, and sudden death. Myocarditis is caused by several infectious and non-infectious agents. Vaccines are also known to cause myocarditis. The use of the coronavirus disease (COVID-19) vaccination was started to combat the severity of the COVID-19 infection and reduce the mortality and morbidity associated with it. The vaccination, however, caused side effects like myocarditis, among others. In order to investigate the association between the COVID-19 vaccination and myocarditis in adults and adolescents, we conducted a literature review by searching three databases: Google Scholar, PubMed, and ScienceDirect. From the published literature, we found that, though it is rare, the various vaccinations available can cause symptoms of myocarditis as a side effect more commonly in patients who have received both doses of a particular vaccine and that there are significant changes in cardiac magnetic resonance imaging (CMRI) and other biochemical markers, with young males being more commonly affected. Further prospective trial-based studies are required to establish a concrete relationship between myocarditis and the COVID-19 vaccine.

Myocarditis Post Moderna Vaccination: Review of Criteria for Diagnosis.

Case reports of myocarditis post-coronavirus disease 2019 (COVID-19) mRNA vaccination have not uniformly reported long-term follow-up beyond 90 days. We present a 23-year-old male who is typical of a patient presenting with myocarditis post-COVID-19 mRNA-1273 Moderna vaccination (young males, onset several days after second dose of the mRNA vaccine, and excellent short term complete recovery). Follow-up at 128 days revealed no residual sequelae in our patient. Although a definitive diagnosis of myocarditis requires an endomyocardial biopsy (EMB), diagnosis is usually made clinically and with imaging in most clinical settings unless part of an approved research protocol or if indicated clinically. We recommend active surveillance and reporting for myocarditis post mRNA vaccination and even consider reporting those with symptom onset beyond 90 days.