Some studies about myocarditis and pericarditis following COVID-19 vaccination raised concerns worldwide. However, the heterogeneous diagnostic criteria for postvaccination inflammatory heart diseases may result in overestimating incidence rates. The aim of this multicentre Italian registry is to evaluate the impact of COVID-19 vaccines on the incidence of myocarditis and pericarditis in the Italian population.

Consecutive patients admitted to Italian hospitals for endomyocardial and/or cardiac magnetic resonance proven acute myocarditis and/or pericarditis in the same period (1 June-31 October) of 2019 and 2021 were enrolled, irrespective of the potential association with the COVID-19 vaccines. Acute pericarditis and/or myocarditis were defined as 'vaccine-related' if clinical presentation occurred within 15 days after COVID-19 vaccination, independently of the dose.

There was a comparable incidence rate ratio (IRR) for inflammatory heart diseases in 2019 and 2021 (2019: IRR 0.67 versus 2021: IRR 0.74, P = 0.45). In particular, the IRR did not differ in myocardial involvement (2019: IRR 0.33 versus 2021: IRR 0.33, P = 1) and pericarditis (2019: IRR 0.37 versus 2021: IRR 0.49, P = 0.09) in both periods. Among 125 cases registered in 2021, 32 (25.6%) were 'vaccine-related'. Among those who experienced 'vaccine-related' myocarditis and/or pericarditis, men with age under 40 years were over-represented (53.12%, P = 0.021).

In a nationwide Italian survey comparing pandemic with prepandemic periods, the overall data do not indicate significant concerns about an increased incidence of pericarditis and myocarditis, suggesting that the vaccine is generally well tolerated for these specific conditions.

The rapid development and deployment of mRNA and non-mRNA COVID-19 vaccines have played a pivotal role in mitigating the global pandemic. Despite their success in reducing severe disease outcomes, emerging concerns about cardiovascular complications have raised questions regarding their safety. This systematic review critically evaluates the evidence on the cardiovascular effects of COVID-19 vaccines, assessing both their protective and adverse impacts, while considering the challenges posed by the limited availability of randomized controlled trial (RCT) data on these rare adverse events. In adherence to PRISMA 2020 guidelines, we conducted a systematic review using the Scopus database, incorporating articles published from January 2020 to July 2024. Our search included terms related to COVID-19 vaccines and cardiovascular conditions. We selected relevant studies from case-control studies, cohort studies, and clinical trials, while excluding descriptive analyses, cross-sectional studies, and conference reports. Case reports were also included due to the limited availability of extensive RCT data on the rare cardiovascular adverse events associated with COVID-19 vaccines. Of the 6037 articles initially screened, 410 were assessed in detail and 175 studies were ultimately included. The review identified a variety of cardiovascular adverse effects associated with COVID-19 vaccines. mRNA vaccines were primarily linked to myocarditis and pericarditis, particularly in younger males, with lower cardiac risks compared to COVID-19 infection. Adenoviral vector vaccines were associated with thrombosis and thrombocytopenia. Inactivated vaccines had fewer severe cardiovascular reports but still presented risks. Takotsubo cardiomyopathy was most commonly observed following mRNA vaccination. Case reports provided valuable additional insights into these rare events, highlighting clinical presentations and potential risk factors not fully captured by larger epidemiological studies. This review reveals a nuanced cardiovascular risk profile for COVID-19 vaccines, with mRNA vaccines linked to rare myocarditis and pericarditis in young males and a higher incidence of Takotsubo cardiomyopathy in females. Adenoviral vaccines show a notable association with thrombosis. Despite these risks, the benefits of vaccination in preventing severe COVID-19 outcomes outweigh the potential complications, underscoring the importance of continued surveillance, case report documentation, and personalized risk assessment. The inclusion of case reports was critical, as they provided valuable real-world data that complemented the findings from large-scale studies and RCTs.

mRNA vaccines represent a milestone in the history of vaccinology, because they are safe, very effective, quick and cost-effective to produce, easy to adapt should the antigen vary, and able to induce humoral and cellular immunity.

To date, only two COVID-19 mRNA and one RSV vaccines have been approved. However, several mRNA vaccines are currently under development for the prevention of human viral (influenza, human immunodeficiency virus [HIV], Epstein-Barr virus, cytomegalovirus, Zika, respiratory syncytial virus, metapneumovirus/parainfluenza 3, Chikungunya, Nipah, rabies, varicella zoster virus, and herpes simplex virus 1 and 2), bacterial (tuberculosis), and parasitic (malaria) diseases.

RNA viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-2, HIV, and influenza, are characterized by high variability, thus creating the need to rapidly adapt the vaccines to the circulating viral strain, a task that mRNA vaccines can easily accomplish; however, the speed of variability may be higher than the time needed for a vaccine to be adapted. mRNA vaccines, using lipid nanoparticles as the delivery system, may act as adjuvants, thus powerfully stimulating innate as well as adaptive immunity, both humoral, which is rapidly waning, and cell-mediated, which is highly persistent. Safety profiles were satisfactory, considering that only a slight increase in prognostically favorable anaphylactic reactions in young females and myopericarditis in young males has been observed.

The COVID-19 pandemic determined a shift in the use of RNA: after having been used in medicine as micro-RNAs and tumor vaccines, the new era of anti-infectious mRNA vaccines has begun, which is currently in great development, to either improve already available, but unsatisfactory, vaccines or develop protective vaccines against infectious agents for which no preventative tools have been realized yet.

Concerns exist that long-term cardiac alterations occur after severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, particularly in patients who were hospitalized in the acute phase or who remain symptomatic. This study investigates potential long-term functional and morphological alterations after SARS-CoV-2 infection.

The authors of this study investigated patients after SARS-CoV-2 infection by using a mobile 1.5T clinical magnetic resonance scanner for cardiac alterations. Cardiac function and dimensions were assessed using a highly efficient cardiac magnetic resonance protocol, which included cine sequences, global longitudinal and circumferential strain assessed by fast-Strain-ENCoded imaging, and T1 and T2 mapping. We assessed symptoms through a questionnaire. Patients were compared with a control group matched for age, gender, body mass index, and body surface area.

Median follow-up time was 395 (192-408) days. The final population included 183 participants (age 48.4 ± 14.3 years, 48.1% male (88/183)). During the acute phase of SARS-CoV-2 infection, 27 patients were hospital-admitted. Forty-two patients reported persistent symptoms (shortness of breath, chest pain, palpitations, or leg edema), and 63 reported impaired exercise tolerance. Left ventricular (LV) functional and morphological parameters were within the normal range. T1- and T2-relaxation times were also within the normal range, indicating that the presence of myocardial edema or fibrosis was unlikely. Persistently symptomatic patients showed a slightly reduced indexed LV stroke volume. Functional parameters remained normal in patients who were hospitalized for SARS-CoV-2, persistently symptomatic, or with ongoing impaired exercise tolerance.

Irrespective of ongoing symptoms or severity of prior illness, patients who have recovered from SARS-CoV-2 infection demonstrate normal functional and morphological cardiac parameters. Long-term cardiac changes due to SARS-CoV-2 infection appear to be rare.

Several vaccines against coronavirus disease 2019 (COVID-19)-caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-have been developed since the COVID-19 pandemic began. Of these, 7 have been approved in the World Health Organization's Emergency Use Listing. However, these vaccines have been reported to have rare or serious adverse cardiovascular effects. This review presents updated information on the adverse cardiovascular effects of the approved COVID-19 vaccines-including inactivated vaccines, protein subunit vaccines, virus-like particles, nucleic acid vaccines, and viral vector vaccines-and the underlying mechanisms.

Cancer patients have an increased risk of cardiovascular outcomes and are susceptible to coronavirus disease 2019 (COVID-19) infection. We aimed to assess the cardiovascular safety of COVID-19 vaccination for cancer patients in South Korea.

We conducted a self-controlled case series study using the K-COV-N cohort (2018-2021). Patients with cancer aged 12 years or older who experienced cardiovascular outcomes were identified. Cardiovascular outcomes were defined as myocardial infarction, stroke, venous thromboembolism (VTE), myocarditis, or pericarditis, and the risk period was 0-28 days after receiving each dose of COVID-19 vaccines. A conditional Poisson regression model was used to calculate the incidence rate ratio (IRR) with 95% confidence interval (CI).

Among 318,105 patients with cancer, 4,754 patients with cardiovascular outcomes were included. The overall cardiovascular risk was not increased (adjusted IRR, 0.99 [95% CI, 0.90-1.08]) during the whole risk period. The adjusted IRRs of total cardiovascular outcomes during the whole risk period according to the vaccine type were 1.07 (95% CI, 0.95-1.21) in the mRNA vaccine subgroup, 0.99 (95% CI, 0.83-1.19) in the ChAdOx1 nCoV-19 vaccine subgroup, and 0.86 (95% CI, 0.68-1.10) in the mix-matched vaccination subgroup. However, in the analysis of individual outcome, the adjusted IRR of myocarditis was increased to 11.71 (95% CI, 5.88-23.35) during the whole risk period. In contrast, no increased risk was observed for other outcomes, such as myocardial infarction, stroke, VTE, and pericarditis.

For cancer patients, COVID-19 vaccination demonstrated an overall safe profile in terms of cardiovascular outcomes. However, caution is required as an increased risk of myocarditis following COVID-19 vaccination was observed in this study.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has led to a global health crisis with substantial mortality and morbidity. To combat the COVID-19 pandemic, various vaccines have been developed, but unexpected serious adverse events including vaccine-induced thrombotic thrombocytopenia, carditis, and thromboembolic events have been reported and became a huddle for COVID-19 vaccination. Vaccine-related myocarditis (VRM) is a rare but significant adverse event associated primarily with mRNA vaccines. This review explores the incidence, risk factors, clinical presentation, pathogenesis, management strategies, and outcomes associated with VRM. The incidence of VRM is notably higher in male adolescents and young adults, especially after the second dose of mRNA vaccines. The pathogenesis appears to involve an immune-mediated process, but the precise mechanism remains mostly unknown so far. Most studies have suggested that VRM is mild and self-limiting, and responds well to conventional treatment. However, a recent nationwide study in Korea warns that severe cases, including fulminant myocarditis or death, are not uncommon in patients with COVID-19 VRM. The long-term cardiovascular consequences of VRM have not been well understood and warrant further investigation. This review also briefly addresses the critical balance between the substantial benefits of COVID-19 vaccination and the rare risks of VRM in the coming endemic era. It emphasizes the need for continued surveillance, research to understand the underlying mechanisms, and strategies to mitigate risk. Filling these knowledge gaps would be vital to refining vaccination recommendations and improving patient care in the evolving COVID-19 pandemic landscape.

In December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the COVID-19 pandemic, with millions of deaths worldwide. Vaccine breakthroughs in late 2020 resulted in the authorization of COVID-19 vaccines. While these vaccines have demonstrated efficacy, evidence from vaccine safety monitoring systems around the globe supported a causal association between COVID-19 vaccines, in particular those using mRNA technology, i.e., Moderna's mRNA-1273 and Pfizer-BioNTech's BNT162b2, and myocarditis.

This paper aims to investigate the epidemiology of mRNA COVID-19 vaccine-induced myocarditis, including age, ethnicity, and gender associations with these vaccines. It also discusses the immunopathophysiological mechanisms of mRNA COVID-19 vaccine-associated myocarditis and outlines principles of diagnosis, clinical presentation, and management.

A literature review was conducted using PubMed, Embase, and Queen Mary University of London Library Services databases. Search terms included "myocarditis," "coronavirus disease 2019," "SARS-CoV-2," "mRNA Covid-19 vaccines," "Covid vaccine-associated myocarditis," "epidemiology," "potential mechanisms," "myocarditis diagnosis," and "myocarditis management."

While the definite mechanism of mRNA COVID-19 vaccine-associated myocarditis remains ambiguous, potential mechanisms include molecular mimicry of spike proteins and activation of the adaptive immune response with dysregulated cytokine expression. Male predominance in COVID-19 vaccine-induced myocarditis may be attributed to sex hormones, variations in inflammatory reactions, coagulation states based on gender, and female-specific protective factors. Moreover, an analysis of diagnostic and management strategies reveals a lack of consensus on acute patient presentation management.

In contrast to viral infections that stand as the predominant etiological factor for myocarditis with more severe consequences, the mRNA COVID-19 vaccination elicits a mild and self-limiting manifestation of the condition. There is currently insufficient evidence to confirm the definite underlying mechanism of COVID-19 vaccine-associated myocarditis. Further research is needed to develop preventive and therapeutic solutions in this context.

To study the association between COVID-19 vaccination and the risk of post-COVID-19 cardiac and thromboembolic complications.

We conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the UK, Spain and Estonia. Vaccine rollout was grouped into four stages with predefined enrolment periods. Each stage included all individuals eligible for vaccination, with no previous SARS-CoV-2 infection or COVID-19 vaccine at the start date. Vaccination status was used as a time-varying exposure. Outcomes included heart failure (HF), venous thromboembolism (VTE) and arterial thrombosis/thromboembolism (ATE) recorded in four time windows after SARS-CoV-2 infection: 0-30, 31-90, 91-180 and 181-365 days. Propensity score overlap weighting and empirical calibration were used to minimise observed and unobserved confounding, respectively.Fine-Gray models estimated subdistribution hazard ratios (sHR). Random effect meta-analyses were conducted across staggered cohorts and databases.

The study included 10.17 million vaccinated and 10.39 million unvaccinated people. Vaccination was associated with reduced risks of acute (30-day) and post-acute COVID-19 VTE, ATE and HF: for example, meta-analytic sHR of 0.22 (95% CI 0.17 to 0.29), 0.53 (0.44 to 0.63) and 0.45 (0.38 to 0.53), respectively, for 0-30 days after SARS-CoV-2 infection, while in the 91-180 days sHR were 0.53 (0.40 to 0.70), 0.72 (0.58 to 0.88) and 0.61 (0.51 to 0.73), respectively.

COVID-19 vaccination reduced the risk of post-COVID-19 cardiac and thromboembolic outcomes. These effects were more pronounced for acute COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough versus unvaccinated SARS-CoV-2 infection.

Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans.

We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects.

We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1).

Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.

Since the original COVID-19 vaccines were developed, abundant clinical trial and real-world evidence evaluating the efficacy, effectiveness, and safety of COVID-19 vaccines has been collected. Knowledge of the relative benefits and risks of COVID-19 vaccines is essential for building trust within target populations, ensuring they remain effectively and safely protected against an enduring infectious threat.

This descriptive review discusses the benefits and risks associated with marketed Moderna, Inc. mRNA-based COVID-19 vaccines, focusing on their real-world effectiveness and safety profiles in various age groups. Adverse events of interest and potential benefits of vaccination are reviewed, including reduced risk for severe COVID-19 and long-term health outcomes, reduced economic and societal costs, and reduced risk for SARS-CoV-2 transmission.

Post-marketing safety and real-world data for Moderna, Inc. COVID-19 mRNA vaccines strongly support a positive benefit - risk profile favoring vaccination across all age groups. Although COVID-19 is no longer considered a global health pandemic, health risks associated with SARS-CoV-2 infection remain high. Concerted efforts are required to engage communities and maintain protection through vaccination. Continued surveillance of emerging variants and monitoring of vaccine safety and effectiveness are crucial for ensuring sustained protection against SARS-CoV-2.

Myocarditis secondary to Coronavirus Disease 2019 (COVID-19) vaccination has been reported in the literature.

This study aimed to characterize the reported cases of myocarditis after COVID-19 vaccination based on age, gender, doses, and vaccine type from published literature and the EudraVigilance database.

We performed an analysis in the EudraVigilance database (until December 18, 2021) and a systematic review of published literature for reported cases of suspected myocarditis and pericarditis (until 30th June 2022) after the COVID-19 vaccination.

EudraVigilance database analysis revealed 16,514 reported cases of myocarditis or pericarditis due to the vaccination with COVID-19 vaccines. The cases of myo- or pericarditis were reported predominantly in the age group of 18-64 (n = 12,214), and in males with a male-to-female (M: F) ratio of 1.7:1. The mortality among myocarditis patients was low, with 128 deaths (2 cases per 10.000.000 administered doses) being reported. For the systematic review, 72 studies with 1026 cases of myocarditis due to the vaccination with COVID-19 vaccines were included. The analysis of published cases has revealed that the male gender was primarily affected with myocarditis post-COVID-vaccination. The median (IQR) age of the myocarditis cases was 24.6 [19.5-34.6] years, according to the systematic review of the literature. Myocarditis cases were most frequently published after the vaccination with m-RNA vaccines and after the second vaccination dose. The overall mortality of published cases was low (n = 5).

Myocarditis is a rare serious adverse event associated with a COVID-19 vaccination. With early recognition and management, the prognosis of COVID-19 vaccine-induced myocarditis is favorable.

There has been a rise in cardiovascular events following the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a strain that caused coronavirus disease 2019 (COVID-19). Although rare, there has been an increase in reports of myocarditis secondary to both individuals infected by the strain and those who received the COVID-19 mRNA vaccine. The focus of this study is to determine the risk of myocarditis associated with the COVID-19 vaccine and SARS-CoV-2 infection. Relevant literature was collected using the search engines PubMed, Google Scholar, and the WHO Global Literature on Coronavirus Disease. Randomized controlled clinical trials and cohort studies reporting the risk of myocarditis induced by SARS-CoV-2 infection and COVID-19 vaccines were used. A meta-analysis was conducted using the inverse variance method using RevMan application software. A meta-analysis of the compiled data showed a mean risk ratio of 4.74 (95% confidence interval (CI) = 2.40 to 9.36; p < 0.0000100), which indicates there is a significant difference in the risk of COVID-19-induced myocarditis in those with unspecified vaccination status compared to the non-infected population. A meta-analysis of the selected data found a mean risk ratio of 5.01 (95% CI = 4.14 to 6.08; p < 0.0000100), indicating a significant difference in the risk of COVID-19-induced myocarditis between those who are unvaccinated and the non-infected population. Upon a meta-analysis of the selected data set, a mean risk ratio of 2.55 (95% CI = 0.840 to 7.74; p = 0.100) was found, indicating no significant difference in the risk of vaccine-induced myocarditis between those with a vaccinated vaccination status and that of the non-infected population. The result of this meta-analysis showed that infection with SARS-CoV-2 in unvaccinated patients carries a statistically significant increased risk of acquiring myocarditis while those receiving the vaccination do not share this same risk.

Post-mRNA coronavirus diseases 2019 (COVID-19) vaccines myocarditis emerged as a rare adverse effect, particularly in adolescents and young adults, and was labeled as such for both vaccines in the summer of 2021. This study aims to summarize the timeline and process of signal detection, substantiation, and quantification of myocarditis cases related to mRNA vaccines in France.

The intensive monitoring plan for COVID-19 vaccine safety was based on case-by-case analysis of all cases collected in the French spontaneous reporting database (Base nationale de pharmacovigilance, BNPV). Cases were evaluated by drug safety medical professionals and discussed at a national level for signal detection purposes. Reported cases were compared to the number of vaccine-exposed persons up to September 30th, 2021. Reporting rates (Rr) of myocarditis per 100,000 injections were calculated and stratified according to age, gender, and injection rank of BNT162b2 and mRNA-1273 vaccines. Poisson distribution was used to compute Rrs 95% Confidence Interval (95% CI).

The case-by-case analysis detected a possible cluster of myocarditis in April 2021 (5 cases, 4 after the 2nd injection). In June 2021, the signal was substantiated with 12 cases (9 related to BNT162b2, and 3 to mRNA-1273). As of September 2021, almost 73 million BNT162b2 and 10 million mRNA-1273 doses had been injected. The Rr per 100,000 injections was 0.5 (0.5-0.6) for BNT162b2 and 1.1 (95% CI 0.9-1.3) for mRNA-1273. The difference among vaccines was more pronounced after the second injection, particularly in men aged 18-24 years (4.3 [3.4-5.5] for BNT162b2 vs. 13.9 [9.2-20.1] for mRNA-1273) and aged 25-29 years (1.9 [1.2-2.9] vs. 7.0 [3.4-12.9]).

The study highlighted the role of the spontaneous reporting system in the detection, assessment, and quantification of myocarditis related to m-RNA vaccines. It suggested from September 2021 that mRNA-1273 was reasonably related to a higher risk of myocarditis than BNT162b2 in people under 30, particularly after the second injection.

The development of safe and effective vaccines against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was a major turning point in the fight against the Coronavirus 2019 (COVID-19) pandemic. However, pharmacovigilance has revealed a small but significant incidence of cardiac inflammation manifesting clinically as myocarditis or pericarditis, particularly in younger vaccine recipients. The incidence is the highest among men under age 40 within a week of receiving the second dose of the mRNA vaccine. In this review, we summarise the evidence for, and guidelines in relation to, SARS-CoV2 vaccine-related myocarditis.

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of 'safe and effective' vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the 'safe and effective' narrative attached to these new technologies. Spike protein pathogenicity, termed 'spikeopathy', whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a 'synthetic virus', is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that 'spikeopathy' can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely.

A minority of patients with severe acute respiratory syndrome coronavirus 2 (COVID-19) develop cardiovascular complications, such as acute cardiac lesions with elevated troponins, de novo systolic heart failure, pericardial effusion and, rarely, acute myocarditis. The prevalence of COVID-19-related myocarditis ranges from 10 to 105 cases per 100,000 COVID-19-infected individuals, with a male predominance (58%) and a median age of 50 years. The etiopathogenetic mechanism is currently unclear, but may involve direct virus-mediated damage or an exaggerated immune response to the virus. Mortality is high, as fulminant myocarditis (FM) develops very often in the form of cardiogenic shock and ventricular arrhythmias. Hence, medical therapy with ACE inhibitors and beta-blockers may not always be sufficient, in which case inotropic and immunosuppressive drugs, most commonly corticosteroids, may be necessary. In this review we analyze the current data on COVID-19 myocarditis, management strategies and therapy, with a brief description of COVID-19 vaccine-associated myocarditis to help clinicians dealing with this peculiar form of myocarditis.

To summarise the available evidence on the risk of myocarditis and/or pericarditis following mRNA COVID-19 vaccination, compared with the risk among unvaccinated individuals in the absence of COVID-19 infection.

Systematic review and meta-analysis.

Electronic databases (Medline, Embase, Web of Science and WHO Global Literature on Coronavirus Disease), preprint repositories (medRxiv and bioRxiv), reference lists and grey literature were searched from 1 December 2020 until 31 October 2022.

Epidemiological studies of individuals of any age who received at least one dose of an mRNA COVID-19 vaccine, reported a risk of myo/pericarditis and compared the risk of myo/pericarditis to individuals who did not receive any dose of an mRNA COVID-19 vaccine.

Two reviewers independently conducted screening and data extraction. The rate of myo/pericarditis among vaccinated and unvaccinated groups was recorded, and the rate ratios were calculated. Additionally, the total number of individuals, case ascertainment criteria, percentage of males and history of SARS-CoV-2 infection were extracted for each study. Meta-analysis was done using a random-effects model.

Seven studies met the inclusion criteria, of which six were included in the quantitative synthesis. Our meta-analysis indicates that within 30-day follow-up period, vaccinated individuals were twice as likely to develop myo/pericarditis in the absence of SARS-CoV-2 infection compared to unvaccinated individuals, with a rate ratio of 2.05 (95% CI 1.49-2.82).

Although the absolute number of observed myo/pericarditis cases remains quite low, a higher risk was detected in those who received mRNA COVID-19 vaccinations compared with unvaccinated individuals in the absence of SARS-CoV-2 infection. Given the effectiveness of mRNA COVID-19 vaccines in preventing severe illnesses, hospitalisations and deaths, future research should focus on accurately determining the rates of myo/pericarditis linked to mRNA COVID-19 vaccines, understanding the biological mechanisms behind these rare cardiac events and identifying those most at risk.

The objective was to investigate the impact of COVID-19 vaccination on anxiety, depression, stress perception, and psychiatric symptoms in patients with schizophrenia, and to explore severity of psychiatric symptoms is associated with vaccine hesitancy in individuals with schizophrenia. Mental health symptoms were evaluated in 273 hospitalized schizophrenia patients who received COVID-19 vaccination, and in 80 patients who refused vaccination, both before and after immunization. The study assessed the effects of vaccination on psychiatric symptoms and the potential association between vaccination behavior and psychological distress. Our findings suggest that COVID-19 vaccination is associated with a small worsening of schizophrenia symptoms in older inpatients. Moreover, vaccination behavior may increase anxiety, depression, and stress perception in hospitalized schizophrenia patients, which has implications for the mental health care team working in the context of the pandemic. The study highlights the importance of monitoring the mental health status of patients with schizophrenia during the COVID-19 pandemic, particularly in relation to vaccination behavior. Further research is needed to better understand the mechanisms underlying the observed effects of COVID-19 vaccination on psychiatric symptoms in patients with schizophrenia.

Acute myocarditis has been described as a relatively rare cardiovascular complication of COVID-19 infection. However, data regarding the risk of myocarditis during the post-acute phase of COVID-19 are scant. We assess the risk of incident myocarditis in COVID-19 survivors within 1 year from the index infection by a systematic review and meta-analysis of the available data.

Data were obtained by searching Medline and Scopus for all studies published at any time up to September 1, 2022, and reporting the long-term risk of incident myocarditis in COVID-19 survivors. Myocarditis risk data were pooled using the Mantel-Haenszel random-effects models with hazard ratio (HR) as the effect measure with 95% confidence interval (CI). Heterogeneity among studies was assessed using the Higgins-Thompson I2 statistic.

Overall, 20,875,843 patients (mean age 56.1 years, 59.1% male) were included in this analysis. Of them, 1,245,167 experienced (and survived) COVID-19 infection. Over a mean follow-up of 9.5 months, myocarditis occurred to 0.21 (95% CI 0.13-0.42) out of 1000 patients survived to COVID-19 infection compared with 0.09 [95% CI 0.07-0.12) out of 1000 control subjects. Pooled analysis revealed that recovered COVID-19 patients presented an increased risk of incident myocarditis (HR 5.16, 95% CI 3.87-6.89; P < 0.0001; I2 = 7.9%) within 1 year from the index infection. The sensitivity analysis confirmed yielded results.

Our findings suggest that myocarditis represents a relatively rare but important post-acute COVID-19 sequelae.

Myocarditis is a rare but significant adverse event associated with COVID-19 vaccination, especially for men under 40. If the risk of myocarditis is not stratified by pertinent risk factors, it may be diluted for high-risk and inflated for low-risk groups. We sought to assess how the risk of myocarditis is reported in the literature.

In accordance with PRISMA standards, we reviewed primary publications in PubMed, Embase, Google Scholar and MedRxiv (through 3/2022) and included studies that estimated the incidence of myocarditis/pericarditis after receiving either the BNT162b2 (Pfizer), mRNA-1273 (Moderna) or Ad26COVS1 (Janssen) vaccine. The main outcome was the percentage of studies using 4, 3, 2, 1 or 0 stratifiers (i.e. sex, age, dose number and manufacturer) when reporting the highest risk of myocarditis. Secondary outcomes included the incidence of myocarditis in males after dose 1 and 2 of the BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccine.

The 29 included studies originated in North America, Europe, Asia, or were Worldwide. Of them, 28% (8/29) used all four stratifiers, and 45% (13/29) used 1 or 0 stratifiers. The highest incidence of myocarditis ranged from 8.1-39 cases per 100,000 persons (or doses) in studies using four stratifiers. Six studies reported an incidence greater than 15 cases per 100,000 persons (or doses) in males aged 12-24 after dose 2 of an mRNA-based vaccine.

Only one in four articles reporting myocarditis used four stratifiers, and men younger than 40 receiving a second dose of an mRNA vaccine are at greatest risk.

Myocarditis is an established but rare adverse event following administration of messenger RNA-based coronavirus disease 2019 (COVID-19) vaccines and is most common in male adolescents and young adults. Symptoms typically develop within a few days of vaccine administration. Most patients have mild abnormalities on cardiac imaging with rapid clinical improvement with standard treatment. However, longer term follow-up is needed to determine whether imaging abnormalities persist, to evaluate for adverse outcomes, and to understand the risk associated with subsequent vaccination. The purpose of the review is to evaluate the current literature related to myocarditis following COVID-19 vaccination, including the incidence, risk factors, clinical course, imaging findings, and proposed pathophysiologic mechanisms.

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic that has affected nearly 600 million people to date across the world. While COVID-19 is primarily a respiratory illness, cardiac injury is also known to occur. Cardiovascular magnetic resonance (CMR) imaging is uniquely capable of characterizing myocardial tissue properties in-vivo, enabling insights into the pattern and degree of cardiac injury. The reported prevalence of myocardial involvement identified by CMR in the context of COVID-19 infection among previously hospitalized patients ranges from 26 to 60%. Variations in the reported prevalence of myocardial involvement may result from differing patient populations (e.g. differences in severity of illness) and the varying intervals between acute infection and CMR evaluation. Standardized methodologies in image acquisition, analysis, interpretation, and reporting of CMR abnormalities across would likely improve concordance between studies. This consensus document by the Society for Cardiovascular Magnetic Resonance (SCMR) provides recommendations on CMR imaging and reporting metrics towards the goal of improved standardization and uniform data acquisition and analytic approaches when performing CMR in patients with COVID-19 infection.

Since publishing successful clinical trial results of mRNA coronavirus disease 2019 (COVID-19) vaccines in December 2020, multiple reports have arisen about cardiovascular complications following the mRNA vaccination. This study provides an in-depth account of various cardiovascular adverse events reported after the mRNA vaccines' first or second dose including pericarditis/myopericarditis, myocarditis, hypotension, hypertension, arrhythmia, cardiogenic shock, stroke, myocardial infarction/STEMI, intracranial hemorrhage, thrombosis (deep vein thrombosis, cerebral venous thrombosis, arterial or venous thrombotic events, portal vein thrombosis, coronary thrombosis, microvascular small bowel thrombosis), and pulmonary embolism.

A systematic review of original studies reporting confirmed cardiovascular manifestations post-mRNA COVID-19 vaccination was performed. Following the PRISMA guidelines, electronic databases (PubMed, PMC NCBI, and Cochrane Library) were searched until January 2022. Baseline characteristics of patients and disease outcomes were extracted from relevant studies.

A total of 81 articles analyzed confirmed cardiovascular complications post-COVID-19 mRNA vaccines in 17,636 individuals and reported 284 deaths with any mRNA vaccine. Of 17,636 cardiovascular events with any mRNA vaccine, 17,192 were observed with the BNT162b2 (Pfizer-BioNTech) vaccine, 444 events with mRNA-1273 (Moderna). Thrombosis was frequently reported with any mRNA vaccine (n = 13,936), followed by stroke (n = 758), myocarditis (n = 511), myocardial infarction (n = 377), pulmonary embolism (n = 301), and arrhythmia (n = 254). Stratifying the results by vaccine type showed that thrombosis (80.8%) was common in the BNT162b2 cohort, while stroke (39.9%) was common with mRNA-1273 for any dose. The time between the vaccination dosage and the first symptom onset averaged 5.6 and 4.8 days with the mRNA-1273 vaccine and BNT162b2, respectively. The mRNA-1273 cohort reported 56 deaths compared to the 228 with BNT162b2, while the rest were discharged or transferred to the ICU.

Available literature includes more studies with the BNT162b2 vaccine than mRNA-1273. Future studies must report mortality and adverse cardiovascular events by vaccine types.

Among the various comorbidities potentially worsening the clinical outcome in patients hospitalized for the acute respiratory syndrome coronavirus-2 (SARS-CoV-2), hypertension is one of the most prevalent. However, the basic mechanisms underlying the development of severe forms of coronavirus disease 2019 (COVID-19) among hypertensive patients remain undefined and the direct association of hypertension with outcome in COVID-19 is still a field of debate. Experimental and clinical data suggest that SARS-CoV-2 infection promotes a rise in blood pressure (BP) during the acute phase of infection. Acute increase in BP and high in-hospital BP variability may be tied with acute organ damage and a worse outcome in patients hospitalized for COVID-19. In this context, the failure of the counter-regulatory renin-angiotensin-system (RAS) axis is a potentially relevant mechanism involved in the raise in BP. It is well recognized that the efficient binding of the Spike (S) protein to angiotensin converting enzyme 2 (ACE2) receptors mediates the virus entry into cells. Internalization of ACE2, downregulation and malfunction predominantly due to viral occupation, dysregulates the protective RAS axis with increased generation and activity of angiotensin (Ang) II and reduced formation of Ang1,7. Thus, the imbalance between Ang II and Ang1-7 can directly contribute to excessively rise BP in the acute phase of SARS-CoV-2 infection. A similar mechanism has been postulated to explain the raise in BP following COVID-19 vaccination ("Spike Effect" similar to that observed during the infection of SARS-CoV-2). S proteins produced upon vaccination have the native-like mimicry of SARS-CoV-2 S protein's receptor binding functionality and prefusion structure and free-floating S proteins released by the destroyed cells previously targeted by vaccines may interact with ACE2 of other cells, thereby promoting ACE2 internalization and degradation, and loss of ACE2 activities.

After the acute infection, COVID-19 can produce cardiac complications as well as long-COVID persistent symptoms. Although vaccination against COVID-19 represented a clear reduction in both mortality and ICU admissions, there is very little information on whether this was accompanied by a decrease in the prevalence of post-COVID cardiac complications. The aim of this study was to analyze the relationship between COVID-19 vaccination and the prevalence of post-COVID cardiac injury assessed by echocardiogram, and long-COVID persistent cardiac symptoms.

All patients who consulted for post-COVID evaluation 14 days after discharge from acute illness were included. Patients with heart disease were excluded. The relationship between complete vaccination scheme (at least two doses applied with 14 days or more since the last dose) and pathological echocardiographic findings, as well as the relationship of vaccination with persistent long-COVID symptoms, were evaluated by multivariate analysis, adjusting for age, sex and clinical variables that would have shown significant differences in univariate analysis.

From 1883 patients, 1070 patients (56.8%) suffered acute COVID-19 without a complete vaccination scheme. Vaccination was associated with lower prevalence of cardiac injury (1.35% versus 4.11%, adjusted OR 0.33; 95% CI 0.17-0.65, p=0.01). In addition, vaccinated group had a lower prevalence of persistent long-COVID symptoms compared to unvaccinated patients (10.7% versus 18.3%, adjusted OR 0.52; 95% CI 0.40-0.69, p<0.001).

Vaccination against COVID-19 was associated with lower post-COVID cardiac complications and symptoms, reinforcing the importance of fully vaccinating the population.

Variable clinical criteria taken by medical professionals across the world for myocarditis following coronavirus disease 2019 (COVID-19) vaccination along with wide variation in treatment necessitates understanding and reviewing the same. A systematic review was conducted to elucidate the clinical findings, laboratory parameters, treatment and outcomes of individuals with myocarditis after COVID-19 vaccination after registering with PROSPERO. Electronic databases including MEDLINE, EMBASE, PubMed, LitCovid, Scopus, ScienceDirect, Cochrane Library, Google Scholar and Web of Science were searched. A total of 85 articles encompassing 2184 patients were analysed. It was a predominantly male (73.4%) and young population (mean age: 25.5 ± 14.2 years) with most having taken an mRNA-based vaccine (99.4%). The mean duration from vaccination to symptom onset was 4.01 ± 6.99 days. Chest pain (90.1%), dyspnoea (25.7%) and fever (11.9%) were the most common symptoms. Only 2.3% had comorbidities. CRP was elevated in 83.3% and cardiac troponin in 97.6% patients. An abnormal ECG was reported in 979/1313 (74.6%) patients with ST-segment elevation being most common (34.9%). Echocardiographic data were available for 1243 patients (56.9%), of whom 288 (23.2%) had reduced left ventricular ejection fraction. Non-steroidal antiinflammatory drugs (76.5%), steroids (14.1%) followed by colchicine (7.3%) were used for treatment. Only 6 patients died among 1317 of whom data were available. Myocarditis following COVID-19 vaccination is often mild, seen more commonly in young healthy males and is followed by rapid recovery with conservative treatment. The emergence of this adverse event calls for harmonizing case definitions and definite treatment guidelines, which require wider research.

Globally, vaccination against COVID-19 has prevented countless infections, hospitalisations and death and represents the most successful intervention in combating the pandemic caused by SARS-CoV-2 infection. Utilisation of existing mRNA vaccine technology has allowed for rapid development of highly immunogenic and effective vaccines. Myopericarditis can occur as an adverse effect of COVID-19 mRNA vaccination, albeit at significantly lower rates than those that occur during SARS-CoV-2 infection. Higher rates are seen in adolescent males, usually within 1-5 days of receiving the second vaccine dose. Although most cases are self-limited and respond to first-line treatment, refractory cases can occur, with a limited evidence base on which to guide management. Here, we present a brief review of COVID-19 mRNA vaccines and associated myopericarditis including risk factors, proposed mechanism, and treatment including management strategies for refractory disease.

Acute myocarditis (especially) and pericarditis have been consistently associated with the administration of vaccines against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), generating anxiety in the general population, uncertainty in the scientific community and obstacles to ambitious mass vaccination programs, especially in foreign countries. Like some of its European counterparts, the Portuguese Society of Cardiology (SPC), through its Studies Committee, decided to take a position on some of the most pressing questions related to this issue: (i) How certain are we of this epidemiological association? (ii) What is the probability of its occurrence? (iii) What are the pathophysiological bases of these inflammatory syndromes? (iv) Should their diagnosis, treatment and prognosis follow the same steps as for typical idiopathic or post-viral acute myopericarditis cases? (v) Is the risk of post-vaccine myocarditis great enough to overshadow the occurrence of serious COVID-19 disease in unvaccinated individuals? In addition, the SPC will issue clinical recommendations and offer its outlook on the various paths this emerging disease may take in the future.

To evaluate the cardiovascular safety of COVID-19 vaccines in the real world.

Studies reported on any COVID-19 vaccine-related cardiovascular events in the population aged ≥12 years between 1 January 2020 and 15 June 2022 were included.

A total of 42 studies were included in this meta-analysis. Myocarditis risk was mainly seen after the second (risk ratio [RR], 2.09; 95% confidence interval [CI]: 1.59-2.58) and third (RR, 2.02; 95% CI: 1.04-2.91) dose. A total of 5 vaccines were analyzed, among which mRNA-1273 (RR, 3.13; 95% CI: 2.11-4.14) and BNT162b2 (RR, 1.57; 95% CI: 1.30-1.85) vaccines were associated with myocarditis risk. No significant increase in risk of myocardial infarction (RR, 0.96) or arrhythmia (RR, 0.98) events was observed following vaccination. The risk of cardiovascular events (myocarditis, RR, 8.53; myocardial infarction, RR, 2.59; arrhythmia, RR, 4.47) after SARS-CoV-2 infection was much higher than after vaccination.

The risk of myocarditis was observed after COVID-19 vaccination, but it was much lower than that following the SARS-CoV-2 infection. No significant increased risk of myocardial infarction or arrhythmia was found after COVID-19 vaccination.

There are multiple reviews on cardiovascular aspects of COVID-19 disease on cardiovascular system in different population but there is lack of evidence about cardiovascular adverse effects of COVID vaccines.

The purpose of this study was to compare the cardiac complications of COVID19 vaccines, based on vaccine type (mRNA, vector-based, and inactivated vaccines).

A systematic search was performed covering PubMed for English case-reports and case-series studies, and finally 100 studies were included.

Myocarditis (with overall rate around 1.62%) was shown to be the most common post-COVID19 immunization cardiac event. More than 90% of post-COVID19 vaccination myocarditis occurred after receiving mRNA vaccines (Moderna & Pfizer-BioNTech), but the report of this event was less in the case of vector-based vaccinations and/or inactivated vaccines. Myocarditis was reported more commonly in men and following the second dose of the immunization. Takotsubo cardiomyopathy (TTC) was reported after mRNA (more commonly) and vector-based vaccinations, with no case report after inactivated vaccines. When mRNA and vector-based vaccinations were used instead of inactivated vaccines, a greater frequency of vaccine-induced thrombotic thrombocytopenia (VITT) and pulmonary emboli (PE) was reported. Myocardial infarction/cardiac arrest was recorded in those beyond the age of 75 years.

The personal and public health benefits of COVID-19 vaccination much outweigh the minor cardiac risks. Reporting bias, regarding more available mRNA vaccines in developed countries, may conflict these results.

We aimed to assess harms (post-vaccine myocarditis and pericarditis) and benefits (preventing severe disease) of COVID-19 vaccination.

We conducted a population-based retrospective cohort study. Using the integrated platform of the vaccination campaign of Lombardy Region (Italy), after the exclusion of 24,188 individuals not beneficiaries of the Regional Health Service, 9,184,146 citizens candidates to vaccine at December 27, 2020 were followed until November 30, 2021 (the loss to follow-up rate was 0.5%). From the date of administration of each vaccine dose to day 28 post-administration, three periods that covered exposure to the first, second, and third dose were defined. The benefit-risk profile of vaccines was performed by comparing the number needed to harm (NNH) and number needed to treat (NNT) by sex, age, and vaccine type.

Incidence rates of myocarditis were 9.9 and 5.2 per million person-months during the exposure and no-exposure periods, respectively, and the incidence rates of pericarditis were 19.5 and 15.9 per million person-months, respectively. The risk of myocarditis was highest following exposure to the second dose of the Moderna vaccine (adjusted HR: 5.5, 95% CI: 3.7 to 8.1). Exposure to the Moderna vaccine was also associated with an increased risk of pericarditis (adjusted HR 2.2, 1.5 to 3.1). NNT was higher than NNH (9471 vs. 7213) for 16 to 19-year-old men who received the Moderna vaccine, while all other sex, age, and vaccine subgroups had a favourable harm-benefit profile.

Men 16 to 19 years of age has the highest rates of myocarditis within a few days after receiving the Moderna vaccines. The balance between harms and benefits was almost always in favour of vaccination.

SARS-CoV-2 has been known to cause multisystemic involvement, gaining entry through ACE-2 and TMPRSS2 receptors. COVID-19 vaccine-associated thyroiditis cases are now being reported. Case Report. Case 1. A 36-year-old woman with a history of right hemithyroidectomy for a benign thyroid nodule, on a stable dose of levothyroxine with euthyroid labs, presented with progressively worsening left neck pain, episodic palpitations, and heat intolerance after the second dose of mRNA1273 (Moderna) vaccine. Examination revealed an enlarged and tender left lobe of the thyroid with suppressed TSH but normal free T4 and ESR, signifying subacute thyroiditis. She was managed conservatively without corticosteroids or beta-blockers, and her symptoms resolved. A follow-up revealed increasing TSH, and levothyroxine was restarted. Case 2. A 33-year-old man with a history of anxiety disorder on Sertraline, presented with a two-week history of palpitations, heat intolerance, and 10-pound weight loss after the second dose of BNT162b2 (Pfizer-BioNTech) vaccine. Examination revealed a normal thyroid gland with no tenderness with elevated thyroid peroxidase and thyroglobulin antibodies. Ultrasound showed a diffusely heterogeneous thyroid with increased vascularity, suggesting silent thyroiditis. Follow-up revealed a hypothyroid phase with high TSH for which levothyroxine supplementation was started. Discussion. COVID-19 vaccine-associated subacute and silent thyroiditis have occurred following all three kinds of available vaccines, characterized by an initial thyrotoxic phase, followed by a hypothyroid phase and a recovery phase. Hypotheses include an immune response triggering thyroid inflammation or cross-reactivity with viral proteins.

COVID-19 vaccine-associated thyroiditis is rare, but long-term monitoring of these patients is essential to ensure appropriate diagnosis and management of the potential hypothyroid phase.

Cardiovascular complications of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection are well-described in the general population but remain limited among pregnant patients. This review summarizes data from case reports, case series, and observational studies of cardiovascular manifestations of corona virus disease 2019 (COVID-19) in pregnant patients and provides recommendations to the cardiovascular clinician regarding management considerations in this vulnerable population. Pregna is an immunocompromised state in which cardiovascular demands are increased. Cardiovascular complications of COVID-19 that have been described in pregnancy include myocardial injury, cardiomyopathy, thromboembolism, pre-eclampsia and arrhythmia. Physiologic and cardiovascular changes in pregnancy predispose pregnant patients with COVID-19 to more severe illness than the general population. Black or Hispanic race, obesity, diabetes, hypertension and lung disease are risk factors for more severe infection, maternal death and adverse perinatal outcomes. Pregnant patients with severe COVID-19 disease compared with non-pregnant age-matched women with COVID infection are more likely to be admitted to the intensive care unit (ICU), receive mechanical ventilation and require advanced mechanical circulatory support. Cardiovascular complications of COVID-19 in pregnant patients requires further attention, particularly given the anticipated increase in birth volume and ongoing nature of COVID-19 pandemic with novel variants. Clinicians should have a lower threshold for cardiac testing and multidisciplinary management in pregnant women with severe COVID-19 disease. Given the persistence of COVID-19 within our communities, diagnostic laboratory and imaging testing for high-risk pregnant patients hospitalized with COVID-19 infection should be routine. We strongly urge the implementation of a cardio-obstetric multidisciplinary team in individually managing these high-risk patients in an effort to improve maternal and fetal outcomes.

Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication.

Baseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured.

Median age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden was reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes.

COVID-19 mRNA vaccine-associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.

Over 10 million doses of COVID-19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post-vaccine myocarditis can result from adaptive humoral and cellular, cardiac-specific inflammation within days and weeks of vaccination. Rates of vaccine-associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with electrocardiographic changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, electrocardiographic changes and elevated troponin levels, CMR is the best non-invasive diagnostic tool with endomyocardial biopsy being restricted to severe cases with heart failure and/or arrhythmias. The management beyond guideline-directed treatment of heart failure and arrhythmias includes non-specific measures to control pain. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS-CoV-2 infection-related hospitalization and death are hugely greater than the risks from post-vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in this area.

Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain.

A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test.

In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09-1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24-1.85]; 1.57 [95% CI, 1.28-1.92], and 1.72 [95% CI, 1.33-2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64-14.36] and 5.97 [95% CI, 4.54-7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25-19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25-5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91-99] versus 16 [95% CI, 12-18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1-9] versus 8 [95% CI, 6-8]).

Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.

The role of a dysregulated renin-angiotensin system (RAS) in the pathogenesis of COVID-19 is well recognized. The imbalance between angiotensin II (Ang II) and Angiotensin1-7 (Ang1,7) caused by the interaction between SARS-CoV-2 and the angiotensin converting enzyme 2 (ACE2) receptors exerts a pivotal role on the clinical picture and outcome of COVID-19. ACE2 receptors are not the exclusive angiotensinases in nature. Other angiotensinases (PRCP, and POP) have the potential to limit the detrimental effects of the interactions between ACE2 and the Spike proteins. In the cardiovascular disease continuum, ACE2 activity tends to decrease, and POP/PRCP activity to increase, from the health status to advanced deterioration of the cardiovascular system. The failure of the counter-regulatory RAS axis during the acute phase of COVID-19 is characterized by a decrease of ACE2 expression coupled to unchanged activity of other angiotensinases, therefore failing to limit the accumulation of Ang II. COVID-19 vaccines increase the endogenous synthesis of SARS-CoV-2 spike proteins. Once synthetized, the free-floating spike proteins circulate in the blood, interact with ACE2 receptors and resemble the pathological features of SARS-CoV-2 ("Spike effect" of COVID-19 vaccines). It has been noted that an increased catalytic activity of POP/PRCP is typical in elderly individuals with comorbidities or previous cardiovascular events, but not in younger people. Thus, the adverse reactions to COVID-19 vaccination associated with Ang II accumulation are generally more common in younger and healthy subjects. Understanding the relationships between different mechanisms of Ang II cleavage and accumulation offers the opportunity to close the pathophysiological loop between the risk of progression to severe forms of COVID-19 and the potential adverse events of vaccination.