The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Predictive Value of Myocardial injury in Patients with COVID-19 Admitted to a Quaternary Hospital in the City of Rio de Janeiro

Abstract Background In Brazil the factors involved in the risk of death in patients with COVID-19 have not been well established. Objective To analyze whether elevations of high-sensitivity troponin I (hTnI) levels influence the mortality of patients with COVID-19. Methods Clinical and laboratory characteristics of hospitalized patients with COVID-19 were collected upon hospital admission. Univariate and binary logistic regression analyzes were performed to assess the factors that influence mortality. P-value<0.05 was considered significant. Results This study analyzed192 patients who received hospital admission between March 16 and June 2, 2020 and who were discharged or died by July 2, 2020. The mean age was 70±15 years, 80 (41.7%) of whom were women. In comparison to those who were discharged, the 54 (28.1%) who died were older (79±12 vs 66±15years; P=0.004), and with a higher Charlson´s index (5±2 vs 3±2; P=0.027). More patients, aged≥60years (P <0.0001), Charlson´s index>1 (P=0.004), lung injury>50% in chest computed tomography (P=0.011), with previous coronary artery disease (P=0.037), hypertension (P=0.033), stroke (P=0.008), heart failure (P=0.002), lymphocytopenia (P=0.024), high D-dimer (P=0.024), high INR (P=0.003), hTnI (P<0.0001), high creatinine (P<0.0001), invasive mechanical ventilation (P<0.0001), renal replacement therapy (P<0.0001), vasoactive amine (P<0.0001), and transfer to the ICU (P=0.001), died when compared to those who were discharged. In logistic regression analysis, elevated hTnI levels (OR=9.504; 95% CI=1.281-70.528; P=0.028) upon admission, and the need for mechanical ventilation during hospitalization (OR=46.691; 95% CI=2.360-923.706; P=0.012) increased the chance of in-hospital mortality. Conclusion This study suggests that in COVID-19 disease, myocardial injury upon hospital admission is a harbinger of poor prognosis.

Interaction of COVID-19 With Common Cardiovascular Disorders.

The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain groups appeared to be at higher risk for severe illness once infected. One such group that immediately came to the forefront and garnered international attention was patients with preexisting cardiovascular disease. Here, we examine the available literature describing the interaction of COVID-19 with a myriad of cardiovascular conditions and diseases, paying particular attention to patients diagnosed with arrythmias, heart failure, and coronary artery disease. We further discuss the association of acute COVID-19 with de novo cardiovascular disease, including myocardial infarction due to coronary thrombosis, myocarditis, and new onset arrhythmias. We will evaluate various biochemical theories to explain these findings, including possible mechanisms of direct myocardial injury caused by the severe acute respiratory syndrome coronavirus-2 virus at the cellular level. Finally, we will discuss the strategies employed by numerous groups and governing bodies within the cardiovascular disease community to address the unprecedented challenges posed to the care of our most vulnerable patients, including heart transplant recipients, end-stage heart failure patients, and patients suffering from acute coronary syndromes, during the early days and height of the COVID-19 pandemic.

Cardiac inflammation associated with COVID-19 mRNA vaccination in patients with and without previous myocarditis.

BACKGROUND: mRNA COVID-19 vaccines have been associated with myocarditis in the general population. However, application of gold standard techniques is often missing, and data about patients with history of myocarditis have not been reported yet. METHODS: We evaluated 21 patients (median age 27, 86% males) for suspected myocarditis after receiving mRNA COVID-19 vaccine. We divided cases with previous diagnosis of myocarditis (PM, N.=7), from naïve controls (NM, N.=14). All patients were investigated thoroughly by cardiac magnetic resonance (100%) with or without endomyocardial biopsy (14%). RESULTS: Overall, 57% of patients met updated Lake Louise criteria and none fulfilled Dallas criteria, with no remarkable differences between groups. Acute coronary syndrome-like presentation was more frequent in NM with earlier normalization of troponin than PM. NM and PM already healed from myocarditis were clinically comparable, whereas PM with active inflammation had subtle presentation and were evaluated for immunosuppressive therapy modulation. None had fulminant myocarditis and/or malignant ventricular arrhythmia at presentation. No major cardiac events occurred by 3 months. CONCLUSIONS: In this study, the suspicion of mRNA COVID-19 vaccine-associated myocarditis was inconstantly confirmed by gold standard diagnostics. Myocarditis was uncomplicated in both PM and NM patients. Larger studies with longer follow-up are needed to validate COVID-19 vaccination in this population.

[Features of the course of non-ST elevation myocardial infarction in patients with a history of COVID-19].

Aim      To study the clinical course of non-ST segment elevation myocardial infarction (NSTEMI) in hospitalized patients after COVID-19 and to evaluate the effect of baseline characteristics of patients on the risk of complications.Material and methods  The study included 209 patients with NSTEMI; 104 of them had had COVID-19. The course of myocardial infarction (MI) was analyzed at the hospital stage, including evaluation of the incidence rate of complications (fatal outcome, recurrent MI, life-threatening arrhythmias and conduction disorders, pulmonary edema, cardiogenic shock, ischemic stroke, gastrointestinal bleeding).Results Mean age of patients after COVID-19 was 61.8±12.2 years vs. 69.0±13.0 in the comparison group (p<0.0001). The groups were comparable by risk factors, clinical data, and severity of coronary damage. Among those who have had СOVID-19, there were fewer patients of the GRACE high risk group (55.8 % vs. 74.3 %; p<0.05). Convalescent COVID-19 patients had higher levels of C-reactive protein and troponin I (p<0.05). The groups did not significantly differ in the incidence of unfavorable NSTEMI course (p>0.05). However, effects of individual factors (postinfarction cardiosclerosis, atrial fibrillation, decreased SpO2, red blood cell concentration, increased plasma glucose) on the risk of complications were significantly greater for patients after COVID-19 than for the control group (p<0.05).Conclusion      Patients with NSTEMI, despite differences in clinical history and laboratory data, are characterized by a similar risk of death at the hospital stage, regardless of the past COVID-19. Despite the absence of statistically significant differences in the incidence of in-hospital complications, in general, post-COVID-19 patients showed a higher risk of complicated course of NSTEMI compared to patients who had not have COVID-19. In addition, for this category of patients, new factors were identified that previously did not exert a clinically significant effect on the incidence of complications: female gender, concentration of IgG to SARS-CoV-2 ≥200.0 U/l, concentration of С-reactive protein ≥40.0 mg/l, total protein <65 g/l. These results can be used for additional stratification of risk for cardiovascular complications in patients with MI and also for development of individual protocols for evaluation and management of NSTEMI patients with a history of COVID-19.

Dysrhythmias associated with COVID-19: Review and management considerations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is known to affect the cardiovascular system. Cardiac manifestations in COVID-19 can be due to direct damage to the myocardium and conduction system as well as by the disease's effect on the various organ systems. These manifestations include acute coronary syndrome, ST- segment elevations, cardiomyopathy, and dysrhythmias. Some of these dysrhythmias can be detrimental to the patient. Therefore, it is important for the emergency physician to be aware of the different arrhythmias associated with COVID-19 and how to manage them. This narrative review discusses the pathophysiology underlying the various arrhythmias associated with COVID-19 and their management considerations.

Primary hypothyroidism with an episode of ventricular tachycardia in a patient with COVID-19: A case report.

RATIONALE: Coronavirus disease 2019 (COVID-19) is a systemic disease with major clinical manifestations in the respiratory system. However, thyroid involvement has also been reported. We present a case of hypothyroidism with ventricular tachycardia following diagnosis with COVID-19. PATIENT CONCERNS: A 77-year-old man was admitted to the isolation ward due to COVID-19. After respiratory support and medical treatment, the patient was successfully weaned off the ventilator. However, an episode of short-run ventricular tachycardia was detected, and primary hypothyroidism was also diagnosed. DIAGNOSIS: Ventricular tachycardia was detected by electrocardiography. INTERVENTIONS: Intravenous amiodarone administration and oral levothyroxine replacement. OUTCOMES: No arrhythmia detected following treatment. LESSONS: Awareness of the association between hypothyroidism and COVID-19 is important in preventing possible complications.

EKG Abnormalities in a Youth Athlete Following COVID-19: It's Not Always Myocarditis!

COVID-19 associated myocarditis following mild infections is rare while incidental findings may be more common. A young athlete fully recovered from a mild COVID-19 infection presented with inferolateral T-wave inversions and left ventricular hypertrophy on imaging. Exercise testing aided in correctly diagnosing the patient with masked systolic hypertension.

Fulminant Myocarditis Following SARS-CoV-2 Infection: JACC Patient Care Pathways.

A 60-year-old woman with a past medical history of asthma presented with fulminant myocarditis 9 days after testing positive for SARS-CoV-2 and 16 days after developing symptoms consistent with COVID-19. Her hospital course was complicated by the need for veno-arterial extracorporeal membrane oxygenation, ventricular arrhythmias, and pseudomonas bacteremia. She ultimately recovered and was discharged to home with normal left ventricular systolic function. Thereafter, she developed symptomatic ventricular tachycardia, for which she received an implantable cardioverter-defibrillator and antiarrhythmic drug therapy.

Prevalence and Clinical Implications of COVID-19 Myocarditis.

The clinical manifestations of COVID-19 are widely variable and may involve several districts. Although the clinical course is mostly characterized by respiratory involvement, up to 30% of hospitalized patients have evidence of myocardial injury due to acute coronary syndrome, cardiac arrhythmias, myocarditis, and cardiogenic shock. In particular, myocarditis is a well-recognized severe complication of COVID-19 and is associated with fulminant cardiogenic shock and sudden cardiac death. In this article, the authors aim to present a comprehensive review about COVID-19-related myocarditis, including clinical characteristics, diagnostic workup, and management.

Pericardial and myocardial involvement after SARS-CoV-2 infection: a cross-sectional descriptive study in healthcare workers.

INTRODUCTION AND OBJECTIVES: The cardiac sequelae of SARS-CoV-2 infection are still poorly documented. We conducted a cross-sectional study in healthcare workers to report evidence of pericardial and myocardial involvement after SARS-CoV-2 infection. METHODS: We studied 139 healthcare workers with confirmed past SARS-CoV-2 infection. Participants underwent clinical assessment, electrocardiography, and laboratory tests, including immune cell profiling and cardiac magnetic resonance (CMR). Clinically suspected pericarditis was diagnosed when classic criteria were present and clinically suspected myocarditis was based on the combination of at least 2 CMR criteria. RESULTS: Median age was 52 (41-57) years, 71.9% were women, and 16.5% were previously hospitalized for COVID-19 pneumonia. On examination (10.4 [9.3-11.0] weeks after infection-like symptoms), participants showed hemodynamic stability. Chest pain, dyspnea or palpitations were present in 41.7% participants, electrocardiographic abnormalities in 49.6%, NT-proBNP elevation in 7.9%, troponin in 0.7%, and CMR abnormalities in 60.4%. A total of 30.9% participants met criteria for either pericarditis and/or myocarditis: isolated pericarditis was diagnosed in 5.8%, myopericarditis in 7.9%, and isolated myocarditis in 17.3%. Most participants (73.2%) showed altered immune cell counts in blood, particularly decreased eosinophil (27.3%; P<.001) and increased cytotoxic T cell numbers (17.3%; P <.001). Clinically suspected pericarditis was associated (P <.005) with particularly elevated cytotoxic T cells and decreased eosinophil counts, while participants diagnosed with clinically suspected myopericarditis or myocarditis had lower (P <.05) neutrophil counts, natural killer-cells, and plasma cells. CONCLUSIONS: Pericardial and myocardial involvement with clinical stability are frequent after SARS-CoV-2 infection and are associated with specific immune cell profiles.

Triple threat: New presentation with diabetic ketoacidosis, COVID-19, and cardiac arrhythmias.

Patients with diabetes have increased susceptibility to infection with Severe acute respiratory syndrome-coronavirus 2 and increased morbidity and mortality from Coronavirus disease 2019 (COVID-19) infection. Mortality from COVID-19 is sometimes caused by cardiac arrhythmias. Electrolyte disturbances in patients with diabetic ketoacidosis (DKA) can increase the risk of cardiac arrhythmias. Despite these correlations, little has been reported about the co-incidence of these three conditions: COVID-19, DKA and cardiac arrhythmias. In this case report we describe two children with COVID-19, new-onset DKA and cardiac arrhythmias. These cases emphasize the importance of close cardiac and electrolyte monitoring in patients with COVID-19 infection.

Cardiac arrhythmias amongst hospitalised Coronavirus 2019 (COVID-19) patients: Prevalence, characterisation, and clinical algorithm to classify arrhythmic risk.

OBJECTIVES: A significant proportion of COVID-19 patients may have cardiac involvement including arrhythmias. Although arrhythmia characterisation and possible predictors were previously reported, there are conflicting data regarding the exact prevalence of arrhythmias. Clinically applicable algorithms to classify COVID patients' arrhythmic risk are still lacking, and are the aim of our study. METHODS: We describe a single-centre cohort of hospitalised patients with a positive nasopharyngeal swab for COVID-19 during the initial Israeli outbreak between 1/2/2020 and 30/5/2020. The study's outcome was any documented arrhythmia during hospitalisation, based on daily physical examination, routine ECG's, periodic 24-hour Holter, and continuous monitoring. Multivariate analysis was used to find predictors for new arrhythmias and create classification trees for discriminating patients with high and low arrhythmic risk. RESULTS: Out of 390 COVID-19 patients included, 28 (7.2%) had documented arrhythmias during hospitalisation, including 23 atrial tachyarrhythmias, combined atrial fibrillation (AF), and ventricular fibrillation, ventricular tachycardia storm, and 3 bradyarrhythmias. Only 7/28 patients had previous arrhythmias. Our study showed a significant correlation between disease severity and arrhythmia prevalence (P < .001) with a low arrhythmic prevalence amongst mild disease patients (2%). Multivariate analysis revealed background heart failure (CHF) and disease severity are independently associated with overall arrhythmia while age, CHF, disease severity, and arrhythmic symptoms are associated with tachyarrhythmias. A novel decision tree using age, disease severity, CHF, and troponin levels was created to stratify patients into high and low risk for developing arrhythmia. CONCLUSIONS: Dominant arrhythmia amongst COVID-19 patients is AF. Arrhythmia prevalence is associated with age, disease severity, CHF, and troponin levels. A novel simple Classification tree, based on these parameters, can discriminate between high and low arrhythmic risk patients.

COVID-19-related arrhythmias and the possible effects of ranolazine.

The COVID-19 pandemic has become a burden to the global healthcare community. Despite the severity of the complications associated with COVID-19, no antiviral agent is yet available for the treatment of this disease. Several studies have reported arrhythmias as one of the numerous manifestations associated with COVID-19 infection. Clinicians use different therapeutic agents in the management of COVID-19 patients with arrhythmias, apart from ranolazine; however, some of these drugs are administered with caution because of their significant side effects. In this study, we reviewed the potential antiarrhythmic effects of ranolazine in the management of cardiac arrhythmias associated with COVID-19. Ranolazine is a second-line drug approved for the treatment of chronic stable angina pectoris. Previous studies have shown that ranolazine produces its beneficial cardiac effects without any significant impact on the body's hemodynamics; hence, blood pressure is not altered. Due to its reduced side effects, ranolazine may be more effective than other drugs in producing the desired relief from COVID-19 related arrhythmias, since it produces its antiarrhythmic effect by modulating sodium, potassium and calcium channels, and suppressing cytokine expression.

A 75-Year-Old Woman with COVID-19 Pneumonia and Wellens Syndrome Diagnosed by Electrocardiography.

BACKGROUND There are increasing reports of cardiovascular complications associated with coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2. Wellens syndrome, or left anterior descending T-wave syndrome, is diagnosed by a pattern of electrocardiographic (ECG) changes that include inverted or biphasic T waves in leads V2-V3. CASE REPORT A 75-year-old woman presented to the emergency department with a 1-week history of fatigue and progressive shortness of breath who acutely decompensated, necessitating mechanical ventilator support. Initial lab workup revealed COVID-19 positivity, which was confirmed by repeat testing. A routine ECG obtained during her hospitalization and compared with her baseline revealed diffuse T-wave inversions of her precordial leads, which was highly suggestive of Wellens syndrome. Cardiac enzymes obtained were slightly elevated and an echocardiogram did not demonstrate wall motion abnormalities. The patient was initiated on non-ST segment elevation myocardial infarction protocol with heparin infusion for 48 hours and dual antiplatelet therapy, in addition to beta blockade. Repeat ECGs showed complete resolution of Wellens syndrome shortly after therapy. CONCLUSIONS Although rare, Wellens syndrome is a significant indicator of left anterior descending artery stenosis and is commonly associated with acute medical illness. COVID-19 pneumonia has been associated with many adverse cardiovascular outcomes, with ischemia and arrhythmia becoming increasingly more common. Diagnosis of Wellens often includes coronary angiography; however, during the current pandemic, many authorities have recommended medical management alone during the acute phase of care, depending on the severity of concomitant illness.

Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era.

COronaVIrus Disease 19 (COVID-19) is caused by the infection of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). Although the main clinical manifestations of COVID-19 are respiratory, many patients also display acute myocardial injury and chronic damage to the cardiovascular system. Understanding both direct and indirect damage caused to the heart and the vascular system by SARS-CoV-2 infection is necessary to identify optimal clinical care strategies. The homeostasis of the cardiovascular system requires a tight regulation of the gene expression, which is controlled by multiple types of RNA molecules, including RNA encoding proteins (messenger RNAs) (mRNAs) and those lacking protein-coding potential, the noncoding-RNAs. In the last few years, dysregulation of noncoding-RNAs has emerged as a crucial component in the pathophysiology of virtually all cardiovascular diseases. Here we will discuss the potential role of noncoding RNAs in COVID-19 disease mechanisms and their possible use as biomarkers of clinical use.