Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an extremely contagious disease whereby the virus damages the host's respiratory tract via entering through the ACE2 receptor. Cardiovascular disorder is being recognized in the majority of COVID-19 patients; yet, the relationship between SARS-CoV-2 and heart failure has not been established. In the present study, SARS-CoV-2 infection was induced in the monkey model. Thereafter, heart tissue samples were collected, and pathological changes were analyzed in the left ventricular tissue by hematoxylin and eosin, trichrome, and immunohistochemical staining specific to T lymphocytes and macrophages. The findings revealed that SARS-CoV-2 infection induces several pathological changes in the heart, which cause cardiomyocyte disarray, mononuclear infiltrates of inflammatory cells, and hypertrophy. Furthermore, collagen-specific staining showed the development of cardiac fibrosis in the interstitial and perivascular regions in the hearts of infected primates. Moreover, the myocardial tissue samples displayed multiple foci of inflammatory cells positive for T lymphocytes and macrophages within the myocardium. These findings suggest the progression of the disease, which can lead to the development of severe complications, including heart failure. Additionally, SARS-CoV-2 antigen staining detected the presence of virus particles in the myocardium. Thus, we found that SARS-CoV-2 infection is characterized by an exaggerated inflammatory immune response in the heart, which possibly contributes to myocardial remodeling and subsequent fibrosis.

Inflammatory activation and immune cell infiltration are main biological characteristics of SARS-CoV-2 infected myocardium.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can target cardiomyocytes (CMs) to directly invade the heart resulting in high mortality. This study aims to explore the biological characteristics of SARS-CoV-2 infected myocardium based on omics by collecting transcriptome data and analyzing them with a series of bioinformatics tools. Totally, 86 differentially expressed genes (DEGs) were discovered in SARS-CoV-2 infected CMs, and 15 miRNAs were discovered to target 60 genes. Functional enrichment analysis indicated that these DEGs were mainly enriched in the inflammatory signaling pathway. After the protein-protein interaction (PPI) network was constructed, several genes including CCL2 and CXCL8 were regarded as the hub genes. SRC inhibitor saracatinib was predicted to potentially act against the cardiac dysfunction induced by SARS-CoV-2. Among the 86 DEGs, 28 were validated to be dysregulated in SARS-CoV-2 infected hearts. Gene Set Enrichment Analysis (GSEA) analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that malaria, IL-17 signaling pathway, and complement and coagulation cascades were significantly enriched. Immune infiltration analysis indicated that 'naive B cells' was significantly increased in the SARS-CoV-2 infected heart. The above results may help to improve the prognosis of patients with COVID-19.

Mechanism of Blood-Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury.

Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.

Frequency of Cardiovascular Complications and Its Association with Prognosis of COVID-19 Patients.

Coronavirus disease 2019 (COVID-19) may lead to acute respiratory disease; cardiovascular, gastrointestinal, and coagulation complications; and even death. One of the major complications is cardiovascular disorders, including arrhythmias, myocarditis, pericarditis, and acute coronary artery disease. The aim of this study was to evaluate the frequency of cardiovascular complications and to determine its association with the prognosis of COVID-19 patients. In a prospective analytic study, 137 hospitalized COVID-19 patients were enrolled. During hospitalization, an electrocardiogram (ECG) was performed every other day, and laboratory tests such as cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were done 0, 6, and 12 hours after admission. These tests were repeated for patients with chest pain or ECG changes. Patients were categorized into three groups (improved, complicated, and expired patients) and assessed for the rate and type of arrhythmias, cardiac complications, lab tests, and outcomes of treatments. There was no significant relationship among the three groups related to primary arrhythmia and arrhythmias during treatment. The most common arrhythmia during hospitalization and after treatment was ST-T fragment changes. There was a significant age difference between the three groups (P = 0.001). There was a significant difference among the three groups for some underlying diseases, including diabetes mellitus (P = 0.003) and hyperlipidemia (P = 0.004). In our study, different types of arrhythmias had no association with patients' outcomes but age over 60 years, diabetes mellitus, and hyperlipidemia played an important role in the prognosis of COVID-19 cases.

Cardiac MRI in Patients with Prolonged Cardiorespiratory Symptoms after Mild to Moderate COVID-19.

Background Myocardial injury and inflammation at cardiac MRI in patients with COVID-19 have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after SARS-CoV-2 infection has been observed and manifests with symptoms such as fatigue and exertional dyspnea. Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. Materials and Methods In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to SARS-CoV-2 infection who had persistent CCS symptoms such as fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. The cardiac MRI protocol included evaluating the T1 and T2 relaxation times, extracellular volume, T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t tests, Mann-Whitney U tests, and χ2 tests were used for statistical analysis. Results Forty-one participants with CCS (mean age, 39 years ± 13 [standard deviation]; 18 men) and 42 control participants (mean age, 39 years ± 16; 26 men) were evaluated. The median time between the initial incidence of mild to moderate COVID-19 not requiring hospitalization and undergoing cardiac MRI was 103 days (interquartile range, 88-158 days). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants (T1 relaxation times: 978 msec ± 23 vs 971 msec ± 25 [P = .17]; T2 relaxation times: 53 msec ± 2 vs 52 msec ± 2 [P = .47]; T2 signal intensity ratios: 1.6 ± 0.2 vs 1.6 ± 0.3 [P = .10]). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated nonischemic LGE, whereas no participants in the control group demonstrated nonischemic LGE (0 of 42 [0%]; P = .07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Conclusion Individuals with chronic COVID-19 syndrome who did not undergo hospitalization for COVID-19 did not demonstrate signs of active myocardial injury or inflammation at cardiac MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lima and Bluemke in this issue.

Taming the Storm in the Heart: Exploring Different Therapeutic Choices Against Myocardial Inflammation in COVID-19.

Mechanism of cardiac injury in COVID-19 is a serious problem and plays critical role in mediating the severity of the disease. However, the mechanistic insights of the induction of the inflammatory signal leading to cardiac injury was poorly understood. However, few recent studies have indicated the involvement of Toll-Like Receptors (TLRs) as the major 'culprit' behind eliciting the initial signal of 'cytokine storm'. As a result, TLRs are now considered as the therapeutic targets to develop efficacious therapeutics. Herein, we present an overall summary on the mechanistic insight of cardiac injury in COVID-19 patients and the therapeutic promises of TLR-targeted therapies.

Heart-rate-variability (HRV), predicts outcomes in COVID-19.

BACKGROUND: Patients with COVID-19 present with a variety of clinical manifestations, ranging from mild or asymptomatic disease to severe illness and death. Whilst previous studies have clarified these and several other aspects of COVID-19, one of the ongoing challenges regarding COVID-19 is to determine which patients are at risk of adverse outcomes of COVID-19 infection. It is hypothesized that this is the result of insufficient inhibition of the immune response, with the vagus nerve being an important neuro-immuno-modulator of inflammation. Vagus nerve activity can be non-invasively indexed by heart-rate-variability (HRV). Therefore, we aimed to assess the prognostic value of HRV, as a surrogate marker for vagus nerve activity, in predicting mortality and intensive care unit (ICU) referral, in patients hospitalized with COVID-19. METHODS: A retrospective cohort study including all consecutive patients (n = 271) diagnosed and hospitalized with COVID-19 between March 2020 and May 2020, without a history of cardiac arrhythmias (including atrial and ventricular premature contractions), pacemaker, or current bradycardia (heart rate <50 bpm) or tachycardia (heart rate >110 bpm). HRV was based on one 10s ECG recorded at admission. 3-week survival and ICU referral were examined. RESULTS: HRV indexed as standard deviation of normal to normal heartbeat intervals (SDNN) predicted survival (H.R. = 0.53 95%CI: 0.31-0.92). This protective role was observed only in patients aged 70 years and older, not in younger patients. HRV below median value also predicted ICU referral within the first week of hospitalization (H.R = 0.51, 95%CI: 0.29-0.90, P = 0.021). CONCLUSION: Higher HRV predicts greater chances of survival, especially in patients aged 70 years and older with COVID-19, independent of major prognostic factors. Low HRV predicts ICU indication and admission in the first week after hospitalization.

COVID-19: Cardio-pulmonary and Vascular Manifestations.

The COVID-19 pandemic is still threatening us, our patients, and the global health care system. Since the first outbreak at the end of 2019 in China, it became rapidly clear that a new variant of a SARS virus, SARS-CoV-2, is threatening our human society worldwide. Since then, the scientific community has accumulated an incredibly large amount of knowledge about the pathophysiology of this virus, primarily affecting the respiratory tract and, in severe cases, subsequently resulting in acute respiratory distress syndrome and multiple organ failure due to uncontrolled systemic inflammatory response syndrome.1 2.

Subclinical myocardial dysfunction in patients recovered from COVID-19.

BACKGROUND: Myocardial injury (MI) can be detected during the acute phase of Coronavirus disease 19 (COVID-19) and is associated with a dismal prognosis. Recent imaging studies described the persistence of cardiac abnormalities after the recovery. The aim of the study was to investigate the spectrum of cardiac abnormalities at mid-term follow-up in patients recovered from COVID-19 using clinical assessment, laboratory tests, and imaging evaluation with comprehensive echocardiography. METHODS: This is an observational, cross-sectional study assessing an unselected cohort of consecutive patients recovered from COVID-19. MI was defined by elevated plasma levels of high sensitive troponin T (hsTnT). At the follow-up, a complete examination including echocardiography was performed. RESULTS: The 123 patients included were divided into two groups according to the presence of MI during hospitalization: group A (without MI) and group B (with MI). After a median of 85 days, group B patients were more frequently symptomatic for dyspnea and had significantly higher values of hsTnT and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP), compared to Group A. No differences between the two groups in left nor right ventricle dimension and ejection fraction were found. However, in group B a significant reduction of mean left ventricle global longitudinal strain was observed (-15.7±.7 vs -18.1± .3 in group A, p < 0.001), together with higher frequency of impaired diastolic function and higher values of pulmonary pressure. CONCLUSIONS: In patients recovered from COVID-19, echocardiography with speckle-tracking analysis may be an useful imaging tool to identify subclinical myocardial dysfunction and potentially guide management strategies.

Cardiovascular magnetic resonance findings in young adult patients with acute myocarditis following mRNA COVID-19 vaccination: a case series.

BACKGROUND: Messenger RNA (mRNA) coronavirus disease of 2019 (COVID-19) vaccine are known to cause minor side effects at the injection site and mild global systemic symptoms in first 24-48 h. Recently published case series have reported a possible association between acute myocarditis and COVID-19 vaccination, predominantly in young males. METHODS: We report a case series of 5 young male patients with cardiovascular magnetic resonance (CMR)-confirmed acute myocarditis within 72 h after receiving a dose of an mRNA-based COVID-19 vaccine. RESULTS: Our case series suggests that myocarditis in this setting is characterized by myocardial edema and late gadolinium enhancement in the lateral wall of the left ventricular (LV) myocardium, reduced global LV longitudinal strain, and preserved LV ejection fraction. All patients in our series remained clinically stable during a relatively short inpatient hospital stay. CONCLUSIONS: In conjunction with other recently published case series and national vaccine safety surveillance data, this case series suggests a possible association between acute myocarditis and COVID-19 vaccination in young males and highlights a potential pattern in accompanying CMR abnormalities.

SARS-CoV2 infection: functional and morphological cardiopulmonary changes in elite handball players.

There is increasing evidence of cardiac involvement post-SARS-CoV-2 infections in symptomatic as well as in oligo- and asymptomatic athletes. This study aimed to characterize the possible early effects of SARS-CoV-2 infections on myocardial morphology and cardiopulmonary function in athletes. Eight male elite handball players (27 ± 3.5 y) with past SARS-CoV-2 infection were compared with four uninfected teammates (22 ± 2.6 y). Infected athletes were examined 19 ± 7 days after the first positive PCR test. Echocardiographic assessment of the global longitudinal strain under resting conditions was not significantly changed (- 17.7% vs. - 18.1%). However, magnetic resonance imaging showed minor signs of acute inflammation/oedema in all infected athletes (T2-mapping: + 4.1 ms, p = 0.034) without reaching the Lake-Louis criteria. Spiroergometric analysis showed a significant reduction in VO2max (- 292 ml/min, - 7.0%), oxygen pulse (- 2.4 ml/beat, - 10.4%), and respiratory minute volume (VE) (- 18.9 l/min, - 13.8%) in athletes with a history of SARS-CoV2 infection (p < 0.05, respectively). The parameters were unchanged in the uninfected teammates. SARS-CoV2 infection caused impairment of cardiopulmonary performance during physical effort in elite athletes. It seems reasonable to screen athletes after SARS-CoV2 infection with spiroergometry to identify performance limitations and to guide the return to competition.

SARS-COV-2 colonizes coronary thrombus and impairs heart microcirculation bed in asymptomatic SARS-CoV-2 positive subjects with acute myocardial infarction.

BACKGROUND: The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients. On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients. Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients. METHODS: This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration. The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI. The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs). MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization. RESULTS: In the study population, ASAP vs. SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p < 0.05), and a higher thrombus grade 5 and thrombus dimensions (p < 0.05). Interestingly, ASAP vs. SANE patients had lower MBG and left ventricular function (p < 0.001), and 39 (84.9%) of ASAP patients had thrombus specimens positive for SARS-COV-2. After PPCI, a MBG 2-3 was present in only 26.1% of ASAP vs. 97.7% of SANE STEMI patients (p < 0.001). Notably, death and nonfatal AMI were higher in ASAP vs. SANE patients (p < 0.05). Finally, in ASAP STEMI patients the thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p < 0.005). Thus, multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients. Intriguingly, in ASAP patients the female vs. male had higher thrombus viral load (15.53 ± 4.5 vs. 30.25 ± 5.51 CT; p < 0.001), and thrombus dimension (4.62 ± 0.44 vs 4.00 ± 1.28 mm2; p < 0.001). ASAP vs. SANE patients had a significantly lower in-hospital survival for MACE following PPCI (p < 0.001). CONCLUSIONS: In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG. These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.

Echocardiographic characteristics of patients with SARS-CoV-2 infection.

BACKGROUND: Myocardial involvement induced by SARS-CoV-2 infection might be important for long-term prognosis. The aim of this observational study was to characterize the myocardial effects during SARS-CoV-2 infections by echocardiography. RESULTS AND METHODS: An extended echocardiographic image acquisition protocol was performed in 18 patients with SARS-CoV-2 infection assessing LV longitudinal, radial, and circumferential deformation including rotation, twist, and untwisting. Furthermore, LV deformation was analyzed in an age-matched control group of healthy individuals (n = 20). The most prevalent finding was a reduced longitudinal strain observed predominantly in more than one basal LV segment (n = 10/14 patients, 71%). This pattern reminded of a "reverse tako-tsubo" morphology that is not typical for other viral myocarditis. Additional findings included a biphasic pattern with maximum post-systolic or negative regional radial strain predominantly basal (n = 5/14 patients, 36%); the absence or dispersion of basal LV rotation (n = 6/14 patients, 43%); a reduced or positive regional circumferential strain in more than one segment (n = 7/14 patients, 50%); a net rotation showing late post-systolic twist or biphasic pattern (n = 8/14 patients, 57%); a net rotation showing polyphasic pattern and/or higher maximum net values during diastole (n = 8/14 patients, 57%). CONCLUSION: Myocardial involvement due to SARS-CoV-2-infection was highly prevalent in the present cohort-even in patients with mild symptoms. It appears to be characterized by specific speckle tracking deformation abnormalities in the basal LV segments. These data set the stage to prospectively test whether these parameters are helpful for risk stratification and for the long-term follow-up of these patients.

Novel effects of acute COVID-19 on cardiac mechanical function: Two case studies.

The spread of the novel coronavirus 2019 (COVID-19) has caused a global pandemic. The disease has spread rapidly, and research shows that COVID-19 can induce long-lasting cardiac damage. COVID-19 can result in elevated cardiac biomarkers indicative of acute cardiac injury, and research utilizing echocardiography has shown that there is mechanical dysfunction in these patients as well, especially when observing the isovolumic, systolic, and diastolic portions of the cardiac cycle. The purpose of this study was to present two case studies on COVID-19 positive patients who had their cardiac mechanical function assessed every day during the acute period to show that cardiac function in these patients was altered, and the damage occurring can change from day-to-day. Participant 1 showed compromised cardiac function in the systolic time, diastolic time, isovolumic time, and the calculated heart performance index (HPI), and these impairments were sustained even 23 days post-symptom onset. Furthermore, Participant 1 showed prolonged systolic periods that lasted longer than the diastolic periods, indicative of elevated pulmonary artery pressure. Participant 2 showed decreases in systole and consequently, increases in HPI during the 3 days post-symptom onset, and these changes returned to normal after day 4. These results showed that daily observation of cardiac function can provide detailed information about the overall mechanism by which cardiac dysfunction is occurring and that COVID-19 can induce cardiac damage in unique patterns and thus can be studied on a case-by-case basis, day-to-day during infection. This could allow us to move toward more personalized cardiovascular medical treatment.

Echocardiography in suspected coronavirus infection: indications, limitations and impact on clinical management.

OBJECTIVES: To describe the use of echocardiography in patients hospitalised with suspected coronavirus infection and to assess its impact on clinical management. METHODS: We studied 79 adults from a prospective registry of inpatients with suspected coronavirus infection at a single academic centre. Echocardiographic indications included abnormal biomarkers, shock, cardiac symptoms, arrhythmia, worsening hypoxaemia or clinical deterioration. Study type (limited or complete) was assessed for each patient. The primary outcome measure was echocardiography-related change in clinical management, defined as intensive care transfer, medication changes, altered ventilation parameters or subsequent cardiac procedures within 24 hours of echocardiography. Coronavirus-positive versus coronavirus-negative patient groups were compared. The relationship between echocardiographic findings and coronavirus mortality was assessed. RESULTS: 56 patients were coronavirus-positive and 23 patients were coronavirus-negative with symptoms attributed to other diagnoses. Coronavirus-positive patients more often received limited echocardiograms (70% vs 26%, p=0.001). The echocardiographic indication for coronavirus-infected patients was frequently worsening hypoxaemia (43% vs 4%) versus chest pain, syncope or clinical heart failure (23% vs 44%). Echocardiography changed management less frequently in coronavirus-positive patients (18% vs 48%, p=0.01). Among coronavirus-positive patients, 14 of 56 (25.0%) died during hospitalisation. Those who died more often had echocardiography to evaluate clinical deterioration (71% vs 24%) and had elevated right ventricular systolic pressures (37 mm Hg vs 25 mm Hg), but other parameters were similar to survivors. CONCLUSIONS: Echocardiograms performed on hospitalised patients with coronavirus infection were often technically limited, and their findings altered patient management in a minority of patients.

Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children.

Importance: The BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine was authorized on May 10, 2021, for emergency use in children aged 12 years and older. Initial reports showed that the vaccine was well tolerated without serious adverse events; however, cases of myocarditis have been reported since approval. Objective: To review results of comprehensive cardiac imaging in children with myocarditis after COVID-19 vaccine. Design, Setting, and Participants: This study was a case series of children younger than 19 years hospitalized with myocarditis within 30 days of BNT162b2 messenger RNA COVID-19 vaccine. The setting was a single-center pediatric referral facility, and admissions occurred between May 1 and July 15, 2021. Main Outcomes and Measures: All patients underwent cardiac evaluation including an electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging. Results: Fifteen patients (14 male patients [93%]; median age, 15 years [range, 12-18 years]) were hospitalized for management of myocarditis after receiving the BNT162b2 (Pfizer) vaccine. Symptoms started 1 to 6 days after receipt of the vaccine and included chest pain in 15 patients (100%), fever in 10 patients (67%), myalgia in 8 patients (53%), and headache in 6 patients (40%). Troponin levels were elevated in all patients at admission (median, 0.25 ng/mL [range, 0.08-3.15 ng/mL]) and peaked 0.1 to 2.3 days after admission. By echocardiographic examination, decreased left ventricular (LV) ejection fraction (EF) was present in 3 patients (20%), and abnormal global longitudinal or circumferential strain was present in 5 patients (33%). No patient had a pericardial effusion. Cardiac magnetic resonance imaging findings were consistent with myocarditis in 13 patients (87%) including late gadolinium enhancement in 12 patients (80%), regional hyperintensity on T2-weighted imaging in 2 patients (13%), elevated extracellular volume fraction in 3 patients (20%), and elevated LV global native T1 in 2 patients (20%). No patient required intensive care unit admission, and median hospital length of stay was 2 days (range 1-5). At follow-up 1 to 13 days after hospital discharge, 11 patients (73%) had resolution of symptoms. One patient (7%) had persistent borderline low LV systolic function on echocardiogram (EF 54%). Troponin levels remained mildly elevated in 3 patients (20%). One patient (7%) had nonsustained ventricular tachycardia on ambulatory monitor. Conclusions and Relevance: In this small case series study, myocarditis was diagnosed in children after COVID-19 vaccination, most commonly in boys after the second dose. In this case series, in short-term follow-up, patients were mildly affected. The long-term risks associated with postvaccination myocarditis remain unknown. Larger studies with longer follow-up are needed to inform recommendations for COVID-19 vaccination in this population.

Cardiac manifestations of COVID-19.

COVID-19 is a novel viral infection caused by severe acute respiratory syndrome (SARS) beta-coronavirus. Epidemiological status changes dynamically as the pandemy is far from ending. Several complications of presented virus may be similar to those observed in other viral infections. Despite lacking data, the heart involvement may be comparable to cardiac complications observed previously in those with SARS as well as Middle East Respiratory Syndrome (MERS). In COVID-19 we observe elevated levels of cardiac biomarkers, such as natriuretic peptides, troponins, myoglobin, C-reactive protein (CRP), interleukin-2 (IL-2), interleukin-6 (IL-6) and ferritin, which is likely the result of myocardial injury. The possible mechanisms of cardiovascular injury include direct toxicity through the viral invasion of cardiac myocytes, ACE-2 receptor-mediated CV (cardiac and endothelial) injury, microvascular dysfunction and thrombosis and cytokine release syndrome (mainly IL-6 mediated). Cardiac manifestations of COVID-19 are focal or global myocardial inflammation, necrosis, ventricular dysfunction, heart failure and arrhythmia.