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Project description:The mRNA vaccines against COVID-19 are highly effective yet associated with rare myocarditis cases, particularly in young males post-second dose. Here we explore the mediators of this adverse effect and its potential solutions, aiming to enhance the safety of future mRNA vaccines. Analysis of post-vaccination plasma highlighted a substantial increase in CXCL10 and IFN-γ levels in patients. Correspondingly, human iPSC-derived macrophages exposed to COVID-19 mRNA vaccines exhibited increased production of these two cytokines. iPSC-derived cardiomyocytes subjected to these cytokines exhibited impaired contractility, arrhythmogenicity, and myocarditis-like gene expression patterns. Genistein, an anti-inflammatory phytoestrogen, notably mitigated these effects, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocarditis. These findings underscore CXCL10 and IFN-γ as key mediators of myocarditis post-mRNA vaccination and propose genistein as a potential therapeutic to mitigate associated cardiovascular risks.
2025-10-20 | GSE254537 | GEO
Project description:The mRNA vaccines against COVID-19 are highly effective yet associated with rare myocarditis cases, particularly in young males post-second dose. Here we explore the mediators of this adverse effect and its potential solutions, aiming to enhance the safety of future mRNA vaccines. Analysis of post-vaccination plasma highlighted a substantial increase in CXCL10 and IFN-γ levels in patients. Correspondingly, human iPSC-derived macrophages exposed to COVID-19 mRNA vaccines exhibited increased production of these two cytokines. iPSC-derived cardiomyocytes subjected to these cytokines exhibited impaired contractility, arrhythmogenicity, and myocarditis-like gene expression patterns. Genistein, an anti-inflammatory phytoestrogen, notably mitigated these effects, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocarditis. These findings underscore CXCL10 and IFN-γ as key mediators of myocarditis post-mRNA vaccination and propose genistein as a potential therapeutic to mitigate associated cardiovascular risks.
2025-10-20 | GSE254538 | GEO
Project description:CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination.
| PRJNA1070987 | ENA
Project description:CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination [mouse]
| PRJNA1070998 | ENA
Project description:CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination [human]
| PRJNA1070999 | ENA
Project description:Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA COVID-19 vaccination. Our study aimed to comprehensively assess potential safety signals related to these cardiac events following the primary and booster doses, with a specific focus on younger populations, including children as young as 6 months of age. Using the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system, we conducted a retrospective pharmacovigilance study analyzing spontaneous reports of myo/pericarditis. We employed both frequentist and Bayesian methods and conducted subgroup analyses by age, sex, and vaccine dose. We observed a higher reporting rate of myo/pericarditis following the primary vaccine series, particularly in males and mainly after the second dose. However, booster doses demonstrated a lower number of reported cases, with no significant signals detected after the fourth or fifth doses. In children and young adults, we observed notable age and sex differences in the reporting of myo/pericarditis cases. Males in the 12-17 and 18-24-year-old age groups had the highest number of cases, with significant signals for both males and females after the second dose. We also identified an increased reporting for a spectrum of cardiovascular symptoms such as chest pain and dyspnea, which increased with age, and were reported more frequently than myo/pericarditis. The present study identified signals of myo/pericarditis and related cardiovascular symptoms after mRNA COVID-19 vaccination, especially among children and adolescents. These findings underline the importance for continued vaccine surveillance and the need for further studies to confirm these results and to determine their clinical implications in public health decision-making, especially for younger populations.
| S-EPMC10419493 | biostudies-literature
Project description:BackgroundClinical trials of the BNT162b2 vaccine, revealed efficacy and safety. We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination.MethodsPatients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort. In all study patients, we excluded past and current COVID-19. Routine clinical and laboratory investigations for common etiologies of myocarditis were performed. Laboratory tests also included troponin and C-reactive protein levels. The diagnosis of myocarditis was established after cardiac MRI.FindingsFive patients presented after the second and one after the first dose of the vaccine. All patients were males with a median age of 23 years. Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection. Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely. All patients responded to the BNT162b2 vaccine. The clinical course was mild in all six patients.InterpretationOur report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization. We believe our information should be interpreted with caution and further surveillance is warranted.
| S-EPMC8162819 | biostudies-literature
Project description:Messenger RNA vaccines are the main COVID-19 vaccines authorized for use in the United States. Side effects are typically minor and transient. We report a case series of four subjects with an acute myocarditis-like illness following mRNA COVID-19 vaccination who were hospitalized at our hospital in Lubbock, Texas. Three patients were young men who presented with acute chest pain after the second dose of the mRNA-1273 vaccine. Another patient was a 53-year-old white woman who presented with acute left arm pain 3 days after the first dose of the mRNA-1273 vaccine. She was later found to have acute decompensated heart failure, and endomyocardial biopsy revealed eosinophilic injury-mediated myocarditis.
| S-EPMC8607537 | biostudies-literature
Project description: Not available
| S-EPMC8385564 | biostudies-literature
Project description:Mycoplasma pneumoniae caused lower respiratory tract infection in children and can exacerbate these infections through the production of various inflammatory factors, with chemokines playing a key role. However, the pathogenesis of this infection is complicated and thus has not been thoroughly studied. We clarified that cytokine expression levels were analyzed in both peripheral blood and bronchoalveolar lavage fluid (BALF), and in vitro assays were conducted using THP-1 macrophages. We discovered that, compared to control children, M. pneumoniae pneumonia (MPP) patients expressed significantly higher levels of CXCL10 both in the peripheral blood and BALF. Moreover, numbers of macrophages, predominantly with a M1 phenotype, were significantly increased in BALFs of children of MPP. In vitro, coculture with IFN-γ or activated CD4+ Th1 cells significantly promoted CXCL10 expressions in THP-1 derived macrophages, which was largely reversed by siRNA-mediated down regulation of STAT1. In addition, IFN-γ-stimulated macrophages greatly promoted the trans-migration of Th1 cells. our data show that Th1 cells-derived IFN-γ augments CXCL10 production in macrophages via the JAK-STAT1 pathway, which subsequently recruits more immune cells like Th1 cells into the infection sites, thereby constituting a positive feedback loop and aggravating the type I inflammatory responses in MPP patients.
| S-EPMC11751459 | biostudies-literature