Cardiac troponins: Mechanisms of release and role in healthy and diseased subjects.

The cardiac troponins (cTns), cardiac troponin C (cTnC), cTnT, and cTnI are key elements of myocardial apparatus, fixed as protein complex on the thin filament of sarcomere and are involved in the regulation of excitation-contraction coupling of cardiomyocytes in the presence of Ca2+ . Circulating cTnT and cTnI (cTns) increase following cardiac tissue necrosis, and they are consolidated biomarkers of acute myocardial infarction (AMI). However, the use of high sensitivity (hs)-immunoassay tests for cTnT and cTnI has made it possible to identify a multitude of other clinical conditions associated with increased circulating levels of cTns. cTns can be measured also in the peripheral circulation of healthy subjects or athletes, suggesting that different mechanisms are involved in the release of cTns in the blood independently of cardiac cell necrosis. In this review, the molecular/cellular mechanisms involved in cTns release in blood and the exploitation of cTnI and cTnT as biomarkers of cardiac adverse events, in addition to cardiac necrosis, are discussed.

Previous and First Detected Cardiovascular Diseases in Patients with New Coronavirus Pneumonia: Possible Mechanisms and Place in a Unified Prognostic Model.

PURPOSE: The aim of this study is to evaluate the frequency of cardiac involvement in patients with coronavirus disease 2019 (COVID-19), possible immune mechanisms of myocardial injury, and the place of cardiovascular pathology among other prognostic factors. METHODS: The study included 86 patients (48 male, 60.2 ± 16.6 years) with COVID-19. In addition to common investigation, examination of troponin T (n = 18) and anti-heart antibodies (AHA, n = 34) were used. The average hospital period was 14 [12; 18] days. RESULTS: The incidence of cardiovascular disease and symptoms was 45.3%. Arrhythmias, heart failure, low-QRS voltage, repolarization disorders, and pericardial effusion were the typical for coronavirus cardiac injury. The level of AHA was increased in 73.5%. Significant (p < 0.05) correlations of AHA level with inflammatory activity, pneumonia, respiratory failure, cardiac symptoms, and death were found. D-dimer >0.5 µg/mL had a sensitivity of 79.2% and specificity of 60% in the prediction of cardiovascular manifestations. Cardiac failure was one of the causes of death in 3/8 patients (37.5%). Lethality in the presence of cardiovascular pathology was 17.9 versus 2.2% without it, p < 0.05. The most powerful prognostic model includes age, diabetes, oxygen therapy volume, maximum leukocyte level, C-reactive protein, and D-dimer (correlation coefficient 0.871, p < 0.001). The model with only age, diabetes, and cardiovascular disease included also had predictive power (correlation coefficient 0.568, p < 0.001). CONCLUSIONS: The cardiovascular pathology is frequent in patients with COVID-19 and strong correlates with the D-dimer. It indicates the high significance of prothrombotic and ischemic mechanisms. High AHA levels may reflect an inflammatory heart injury. The cardiovascular pathology is associated with higher lethality.

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey.

BACKGROUND: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. METHODS: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. RESULTS: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. CONCLUSION: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths.

SARS-CoV-2 infection in an infant with severe dilated cardiomyopathy.

A four- and a half-month-old girl with severe dilated cardiomyopathy due to neonatal enterovirus myocarditis, treated with diuretics and milrinone for the past 4 months, was infected with SARS-CoV-2. The disease course was characterised by high fever and gastrointestinal symptoms. Cardiac function, as measured by echocardiography, remained stable. The treatment focused on maintaining a normal heart rate and a stable fluid balance. In children with severe underlying cardiac disease, even a mild SARS-CoV-2 infection can require close monitoring and compound treatment.

The Clinical Characteristics and Risk Factors of Severe COVID-19.

OBJECTIVE: We aim to investigate the clinical characteristics and risk factors for the severe cases of coronavirus disease 2019 (COVID-19) in comparison with the non-severe patients. METHODS: We searched PubMed, EMBASE, Web of Science, and CNKI to collect all relevant studies published before July 26, 2020, and a total of 30 papers were included in this meta-analysis. RESULTS: In the severe COVID-19 patients, 60% (95% CI = 56-64%) were male, 25% (95% CI = 21-29%) were over 65 years old, 34% (95% CI = 24-44%) were obese, and 55% (95% CI = 41-70%) had comorbidities. The most prevalent comorbidities were hypertension (34%, 95% CI = 25-44%), diabetes (20%, 95% CI = 15-25%), and cardiovascular disease (CVD; 12%, 95% CI = 9-16%). The most common blood test abnormalities were elevated C-reactive protein (CRP; 87%, 82-92%), decreased lymphocyte count (68%, 58-77%), and increased lactate dehydrogenase (69%, 95% CI = 57-81%). In addition, abnormal laboratory findings revealing organ dysfunctions were frequently observed in the severe cases, including decrease in albumin (43%, 95% CI = 24-63%) and increase in aspartate aminotransferase (47%, 95% CI = 38-56%), alanine aminotransferase (28%, 95% CI = 16-39%), troponin I/troponin T (TnI/TnT; 29%, 95% CI = 13-45%), and serum Cr (SCr; 10%, 95% CI = 5-15%). CONCLUSION: The male, elderly and obese patients and those with any comorbidities, especially with hypertension, diabetes, and CVD, were more likely to develop into severe cases. But the association between hypertension, diabetes, CVD, and severity of COVID-19 was declined by the increase of age. A significant elevation in cardiac TnI/TnT, the hepatic enzymes, and SCr and the reduction in lymphocytes with elevated CRPs are important markers for the severity. Specific attention should be given to the elderly male and obese patients and those with indications of severe immune injury in combination with bacterial infection and indication of multi-organ dysfunction or damages.

Establishing a model for predicting the outcome of COVID-19 based on combination of laboratory tests.

INTRODUCTION: There are currently no satisfactory methods for predicting the outcome of Coronavirus Disease-2019 (COVID-19). The aim of this study is to establish a model for predicting the prognosis of the disease. METHODS: The laboratory results were collected from 54 deceased COVID-19 patients on admission and before death. Another 54 recovered COVID-19 patients were enrolled as control cases. RESULTS: Many laboratory indicators, such as neutrophils, AST, γ-GT, ALP, LDH, NT-proBNP, Hs-cTnT, PT, APTT, D-dimer, IL-2R, IL-6, IL-8, IL-10, TNF-α, CRP, ferritin and procalcitonin, were all significantly increased in deceased patients compared with recovered patients on admission. In contrast, other indicators such as lymphocytes, platelets, total protein and albumin were significantly decreased in deceased patients on admission. Some indicators such as neutrophils and procalcitonin, others such as lymphocytes and platelets, continuously increased or decreased from admission to death in deceased patients respectively. Using these indicators alone had moderate performance in differentiating between recovered and deceased COVID-19 patients. A model based on combination of four indicators (P = 1/[1 + e-(-2.658+0.587×neutrophils - 2.087×lymphocytes - 0.01×platelets+0.004×IL-2R)]) showed good performance in predicting the death of COVID-19 patients. When cutoff value of 0.572 was used, the sensitivity and specificity of the prediction model were 90.74% and 94.44%, respectively. CONCLUSIONS: Using the current indicators alone is of modest value in differentiating between recovered and deceased COVID-19 patients. A prediction model based on combination of neutrophils, lymphocytes, platelets and IL-2R shows good performance in predicting the outcome of COVID-19.