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1.
Cardiovasc Diabetol ; 20(1): 218, 2021 11 06.
Article in English | MEDLINE | ID: covidwho-1503722

ABSTRACT

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.


Subject(s)
COVID-19/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Disease Management , Heart Failure/epidemiology , Mass Screening/methods , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Glycated Hemoglobin A/metabolism , Heart Failure/blood , Heart Failure/diagnosis , Humans , Mass Screening/trends , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis
2.
Sci Rep ; 11(1): 19193, 2021 09 28.
Article in English | MEDLINE | ID: covidwho-1442802

ABSTRACT

Outside of the ongoing COVID-19 pandemic, tuberculosis is the leading cause of infectious disease mortality globally. Currently, there is no commercially available point-of-care diagnostic that is rapid, inexpensive, and highly sensitive for the diagnosis of active tuberculosis disease. Here we describe the development and optimization of a novel, highly sensitive prototype bioelectronic tuberculosis antigen (BETA) assay to detect tuberculosis-specific antigen, CFP10, in small-volume serum and urine samples. In this proof-of-concept study we evaluated the performance of the BETA assay using clinical specimens collected from presumptive tuberculosis patients from three independent cohorts. Circulating CFP10 antigen was detected in ALL serum (n = 19) and urine (n = 3) samples from bacteriologically confirmed tuberculosis patients who were untreated or had less than one week of treatment at time of serum collection, successfully identifying all culture positive tuberculosis patients. No CFP10 antigen was detected in serum (n = 7) or urine (n = 6) samples from individuals who were determined to be negative for tuberculosis disease. Additionally, antigen quantification using the BETA assay of paired serum samples collected from tuberculosis patients (n = 8) both before and after treatment initiation, indicate consistently declining within-person levels of CFP10 antigen during treatment. This novel, low-cost assay demonstrates potential as a rapid, non-sputum-based, point-of-care tool for the diagnosis of tuberculosis disease.


Subject(s)
Diagnostic Tests, Routine/methods , Peptide Fragments , Tuberculosis/diagnosis , Antigens, Bacterial/blood , Antigens, Bacterial/isolation & purification , Antigens, Bacterial/urine , Mycobacterium tuberculosis/immunology , Peptide Fragments/blood , Peptide Fragments/isolation & purification , Peptide Fragments/urine , Sensitivity and Specificity , Tuberculosis, Pulmonary/diagnosis
4.
Ann R Coll Surg Engl ; 103(8): 604-611, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1379818

ABSTRACT

INTRODUCTION: A novel hyperinflammatory syndrome has emerged in the paediatric population: paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS). Up to 50% of patients develop shock with cardiac dysfunction but presentation with acute abdominal pain is common and difficult to distinguish from appendicitis. METHOD: Prospective case series of PIMS-TS patients presenting to a single UK tertiary paediatric centre. RESULTS: As of 16 September 2020, 89 patients have presented with PIMS-TS to our institution; 19 (21.3%) were referred for surgical review. Pyrexia and acute abdominal pain were seen in all 19 patients. Diarrhoea was reported in 14 (73%) and vomiting in 12 (63%). On examination, eight (42%) had right abdominal tenderness, of which five had right iliac fossa (RIF) peritonism. C-reactive protein (CRP) was universally raised: median 176 (15-463)mg/l. Abdominal imaging was performed in 17 (89%), with 11 undergoing abdominal ultrasonography (65%) and 8 abdominal computed tomography (47%); two required both. Findings included nonspecific features of inflammation in the RIF. Eight patients (42%) had an abnormal echocardiogram at admission. Two (10%) patients, with classical signs and symptoms of appendicitis, underwent appendicectomy without radiological imaging and were subsequently diagnosed with PIMS-TS. During the same period, 18 patients underwent appendicectomy for histologically confirmed appendicitis. Serum CRP and ferritin levels were significantly higher in the PIMS-TS cohort compared with children with appendicitis. CONCLUSIONS: PIMS-TS is a novel paediatric condition that may mimic appendicitis. It should be considered in patients presenting with abdominal pain to avoid unnecessary surgery in children at risk of cardiovascular instability.


Subject(s)
COVID-19/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Appendectomy , Appendicitis/diagnosis , Appendicitis/surgery , Biomarkers/blood , C-Reactive Protein/analysis , Child , Child, Preschool , Diagnosis, Differential , Female , Ferritins/analysis , Fibrin Fibrinogen Degradation Products/analysis , Humans , Infant , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies
5.
Am Heart J ; 242: 61-70, 2021 12.
Article in English | MEDLINE | ID: covidwho-1356105

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. METHODS: Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. RESULTS: Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. CONCLUSIONS: CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. TRIAL REGISTRATION: COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232.


Subject(s)
COVID-19/complications , Cicatrix/diagnostic imaging , Heart Diseases/diagnostic imaging , Magnetic Resonance Imaging, Cine/methods , Ventricular Dysfunction, Left/diagnostic imaging , Adult , Aged , Biomarkers/blood , COVID-19/blood , Cicatrix/etiology , Female , Gadolinium , Heart Diseases/blood , Heart Diseases/etiology , Heart Diseases/physiopathology , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , Severity of Illness Index , Stroke Volume , Survivors , Troponin T/blood , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology
6.
Am J Emerg Med ; 48: 307-311, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1293516

ABSTRACT

BACKGROUND AND AIM: Occasionally, children with COVID-19 may develop arrhythmia, myocarditis, and cardiogenic shock involving multisystemic inflammatory syndrome in children (MIS-C). This study aimed to identify the laboratory parameters that may predict early cardiovascular involvement in these patients. MATERIALS AND METHODS: Data of 320 pediatric patients, aged 0-18 years (average age, 10.46 ± 5.77 years; 156 female), with positive COVID-19 reverse transcription-polymerase chain reaction test and with cardiac biomarkers at the time of admission to the pediatric emergency department were retrospectively scanned. The age, sex, COVID-19-associated symptoms, pro-brain natriuretic peptide (proBNP), CK-MB, and troponin I levels of the patients were recorded. RESULTS: Fever was noted in 58.1% of the patients, cough in 29.7%, diarrhea in 7.8%, headache in 14.7%, sore throat in 17.8%, weakness in 17.8%, abdominal pain in 5%, loss of taste in 4.1%, loss of smell in 5.3%, nausea in 3.4%, vomiting in 3.8%, nasal discharge in 4.4%, muscle pain in 5%, and loss of appetite in 3.1%. The proBNP value ≥282 ng/L predicted the development of MIS-C with 100% sensitivity and 93% specificity [AUC: 0.985 (0.959-1), P < 0.001]; CK-MB value ≥2.95 with 80% sensitivity and 77.6% specificity [AUC: 0.792 (0.581-1), P = 0.026]; and troponin I value ≥0.03 with 60% sensitivity and 99.2% specificity [AUC: 0.794 (0.524-1)]. CONCLUSIONS: Cardiac markers (proBNP and troponin I), especially proBNP, could be used to detect early diagnosis of cardiac involvement and/or MIS-C in pediatric patients with COVID-19 and to predict related morbidity and mortality.


Subject(s)
COVID-19/blood , COVID-19/complications , Creatine Kinase, MB Form/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Systemic Inflammatory Response Syndrome/blood , Troponin I/blood , Adolescent , COVID-19/etiology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Predictive Value of Tests , Prognosis , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/etiology
7.
Front Immunol ; 12: 625732, 2021.
Article in English | MEDLINE | ID: covidwho-1291351

ABSTRACT

The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this ACE2 gene dysregulation mainly affects the monocytes, which also show a lower expression of membrane ACE2 protein. Moreover, soluble ACE2 (sACE2) plasma concentrations are lower in prolonged viral shedders than in healthy controls, while the concentration of sACE2 returns to normal levels in short viral shedders. In the plasma of prolonged viral shedders, we also found higher concentrations of Ang II and angiotensin I (Ang I). On the other hand, the plasma levels of Ang-(1-7) remains almost stable in prolonged viral shedders but seems insufficient to prevent the adverse effects of Ang II accumulation. Altogether, these data evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.


Subject(s)
Angiotensin II/blood , Angiotensin I/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , Peptide Fragments/blood , Adult , Angiotensin-Converting Enzyme 2/genetics , COVID-19/virology , Female , Gene Expression Profiling , HLA-DR Antigens , Humans , Lipopolysaccharide Receptors , Male , Middle Aged , Monocytes/immunology , Monocytes/metabolism , Pilot Projects , Prospective Studies , RNA, Messenger , Virus Shedding
8.
Sci Prog ; 104(2_suppl): 368504211026119, 2021 06.
Article in English | MEDLINE | ID: covidwho-1288516

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a vast number of infections and deaths that deeply affect the world. When the virus encounters the host cell, it binds to angiotensin-converting enzyme 2, then the S protein of the virus is broken down by the transmembrane protease serine 2 with the help of furin, allowing the virus to enter the cell. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. Therefore, the aim of this study is to investigate the relationship between circulating furin levels, disease severity, and inflammation in patients with SARS-CoV-2. A total of 52 SARS-CoV-2 patients and 36 healthy control participants were included in this study. SARS- CoV-2 patients were scored by the disease activity score. Serum furin, presepsin, and interleukin-6 (IL-6) levels were assessed using an enzyme-linked immunosorbent assay. The mean furin, presepsin, and IL-6 levels were significantly higher in the peripheral blood of SARS-CoV-2 compared to the controls (p < 0.001). There were close positive relationship between serum furin and IL-6, furin and presepsin, and furin and disease severity (r = 0.793, p < 0001; r = 0.521, p < 0.001; and r = 0,533, p < 0.001, respectively) in patients with SARS-CoV-2. These results suggest that furin may contribute to the exacerbation of SARS-CoV-2 infection and increased inflammation, and could be used as a predictor of disease severity in COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/pathology , Furin/blood , Interleukin-6/blood , Lipopolysaccharide Receptors/blood , Peptide Fragments/blood , SARS-CoV-2 , Adult , Aged , Biomarkers/blood , Female , Humans , Lipopolysaccharide Receptors/genetics , Lipopolysaccharide Receptors/metabolism , Male , Middle Aged , Peptide Fragments/genetics , Peptide Fragments/metabolism
9.
Eur J Clin Invest ; 51(9): e13629, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1286672

ABSTRACT

Background During COVID-19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should establish clear and objective criteria to stratify COVID-19 patients at high risk of in-hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all-cause in-hospital mortality in COVID-19 patients. Design observational study. Results Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00-1.65, P = .050); each increment of 803 ng/L of N-terminal pro-B-type natriuretic peptide (NT-proBNP) corresponded to a HR of 1.24 (95% CI 1.11-1.39, P < .001); each increment of 58 ng/L of interleukin (IL)-6 corresponded to a HR of 1.23 (95% CI 1.09-1.40, P < .001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10-1.37, P < .001). According to the calculated cut-points for age (≥70 years), NT-proBNP (≥803 ng/L), IL-6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97-4.45, P < .001). Conclusion In COVID-19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in-hospital mortality regardless of other comorbidities.


Subject(s)
COVID-19/mortality , Hospital Mortality , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Age Factors , Aged , Biomarkers , COVID-19/blood , Female , Humans , Italy , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , SARS-CoV-2
10.
Arch Cardiovasc Dis ; 114(5): 394-406, 2021 May.
Article in English | MEDLINE | ID: covidwho-1240129

ABSTRACT

BACKGROUND: Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population. AIMS: To assess the burden and impact of cardiovascular comorbidities in women with COVID-19. METHODS: All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death. RESULTS: Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure. CONCLUSIONS: Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.


Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Aged , Asthma/epidemiology , Biomarkers , Cardiovascular Diseases/blood , Comorbidity , Diabetes Mellitus/epidemiology , Female , France/epidemiology , Hospital Mortality , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk Factors , Sex Distribution , Smoking/epidemiology , Troponin/blood
11.
Am J Emerg Med ; 49: 62-70, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1233343

ABSTRACT

OBJECTIVE: A meta-analysis of laboratory cardiac markers for multisystem inflammatory syndrome in children (MIS-C) was performed in patients with coronavirus disease 2019 (COVID-19). METHODS: Eight databases were searched until April 10, 2021, for studies on cardiac markers, including B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), troponin, aspartate aminotransferase (AST), in MIS-C patients. RESULTS: Of the 2583 participants enrolled in 24 studies, 1613 patients were diagnosed with MIS-C. MIS-C patients exhibited higher BNP levels than patients with non-severe COVID-19 [SMD (95% CI): 1.13 (0.48, 1.77), p < 0.05]. No significant differences in BNP levels were observed between patients with MIS-C and severe COVID-19 [SMD (95% CI): 0.29 (-0.07, 0.65), p = 0.117]. Comparisons of MIS-C patients to all COVID-19 patients revealed no significant differences in levels of troponin [SMD (95% CI): 0.13 (-0.07, 0.32), p = 0.212] or AST [SMD (95% CI): 0.10 (-0.11, 0.31), p = 0.336]. Compared to patients with non-severe MIS-C, those with severe MIS-C exhibited higher levels of BNP [SMD (95% CI): 0.26 (0.04, 0.48), p < 0.05], but no differences in troponin [SMD (95% CI): 0.05 (-0.06, 0.16) p = 0.387] or AST [SMD (95% CI): 0.19 (-0.34, 0.71), p = 0.483] were observed. Moreover, there was no significant difference in BNP [SMD (95% CI): -0.21 (-1.07, 0.64), p = 0.624] or troponin [SMD (95% CI): -0.07 (-0.45, 0.31), p = 0.710] between MIS-C with and without coronary artery abnormality. Sensitivity analyses were performed to assess stability. No publication bias was detected based on Begg's test. CONCLUSIONS: The key cardiac marker that showed differences between patients with MIS-C/non-severe COVID-19 and between patients with severe/non-severe MIS-C was BNP. Other markers, such as troponin and AST, did not exhibit notable differences in indicating cardiac injury between patients with MIS-C and COVID-19.


Subject(s)
COVID-19/complications , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Aspartate Aminotransferases/blood , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/pathology , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Systemic Inflammatory Response Syndrome/pathology , Troponin/blood
12.
Am J Physiol Lung Cell Mol Physiol ; 321(1): L213-L218, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1234311

ABSTRACT

The renin-angiotensin system (RAS) is fundamental to COVID-19 pathobiology, due to the interaction between the SARS-CoV-2 virus and the angiotensin-converting enzyme 2 (ACE2) coreceptor for cellular entry. The prevailing hypothesis is that SARS-CoV-2-ACE2 interactions lead to an imbalance of the RAS, favoring proinflammatory angiotensin II (ANG II)-related signaling at the expense of the anti-inflammatory ANG-(1-7)-mediated alternative pathway. Indeed, multiple clinical trials targeting this pathway in COVID-19 are underway. Therefore, precise measurement of circulating RAS components is critical to understand the interplay of the RAS on COVID-19 outcomes. Multiple challenges exist in measuring the RAS in COVID-19, including improper patient controls, ex vivo degradation and low concentrations of angiotensins, and unvalidated laboratory assays. Here, we conducted a prospective pilot study to enroll 33 patients with moderate and severe COVID-19 and physiologically matched COVID-19-negative controls to quantify the circulating RAS. Our enrollment strategy led to physiological matching of COVID-19-negative and COVID-19-positive moderate hypoxic respiratory failure cohorts, in contrast to the severe COVID-19 cohort, which had increased severity of illness, prolonged intensive care unit (ICU) stay, and increased mortality. Circulating ANG II and ANG-(1-7) levels were measured in the low picomolar (pM) range. We found no significant differences in circulating RAS peptides or peptidases between these three cohorts. The combined moderate and severe COVID-19-positive cohorts demonstrated a mild reduction in ACE activity compared with COVID-19-negative controls (2.2 ± 0.9 × 105 vs. 2.9 ± 0.8 × 105 RFU/mL, P = 0.03). These methods may be useful in designing larger studies to physiologically match patients and quantify the RAS in COVID-19 RAS augmenting clinical trials.


Subject(s)
Angiotensin II/blood , Angiotensin I/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , Peptide Fragments/blood , Renin-Angiotensin System , Respiratory Insufficiency/blood , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/pathology , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Pilot Projects , Respiratory Insufficiency/pathology , Respiratory Insufficiency/physiopathology
14.
Circ J ; 85(6): 921-928, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1216947

ABSTRACT

BACKGROUND: This study investigated the effects of age on the outcomes of coronavirus disease 2019 (COVID-19) and on cardiac biomarker profiles, especially in patients with cardiovascular diseases and/or risk factors (CVDRF).Methods and Results:A nationwide multicenter retrospective study included 1,518 patients with COVID-19. Of these patients, 693 with underlying CVDRF were analyzed; patients were divided into age groups (<55, 55-64, 65-79, and ≥80 years) and in-hospital mortality and age-specific clinical and cardiac biomarker profiles on admission evaluated. Overall, the mean age of patients was 68 years, 449 (64.8%) were male, and 693 (45.7%) had underlying CVDRF. Elderly (≥80 years) patients had a significantly higher risk of in-hospital mortality regardless of concomitant CVDRF than younger patients (P<0.001). Typical characteristics related to COVID-19, including symptoms and abnormal findings on baseline chest X-ray and computed tomography scans, were significantly less prevalent in the elderly group than in the younger groups. However, a significantly (P<0.001) higher proportion of elderly patients were positive for cardiac troponin (cTn), and B-type natriuretic peptide (BNP) and N-terminal pro BNP (NT-proBNP) levels on admission were significantly higher among elderly than younger patients (P<0.001 and P=0.001, respectively). CONCLUSIONS: Elderly patients with COVID-19 had a higher risk of mortality during the hospital course, regardless of their history of CVDRF, were more likely to be cTn positive, and had significantly higher BNP/NT-proBNP levels than younger patients.


Subject(s)
COVID-19/blood , Cardiovascular Diseases/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin/blood , Adult , Age Factors , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/mortality , Cardiovascular Diseases/therapy , Female , Heart Disease Risk Factors , Hospital Mortality , Humans , Japan , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment
15.
Acta Anaesthesiol Scand ; 65(6): 761-769, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1138068

ABSTRACT

INTRODUCTION: Critically ill Covid-19 pneumonia patients are likely to develop the sequence of acute pulmonary hypertension, right ventricular (RV) strain, and eventually RV failure due to known pathophysiology (endothelial inflammation plus thrombo-embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. This study aimed to investigate the occurrence of acute pulmonary hypertension (aPH) as per established trans-thoracic echocardiography (TTE) criteria in Covid-19 patients receiving intensive care and to explore whether short-term outcomes are affected by the presence of aPH. METHODS: Medical records were reviewed for patients treated in the intensive care units at a tertiary university hospital over a month. The presence of aPH on the TTE was noted, and plasma NTproBNP and troponin were measured as markers of cardiac failure and myocardial injury, respectively. Follow-up data were collected 21 d after the performance of TTE. RESULTS: In total, 26 of 67 patients (39%) had an assessed systolic pulmonary artery pressure of > 35 mmHg (group aPH), meeting the TTE definition of aPH. NTproBNP levels (median [range]: 1430 [102-30 300] vs. 470 [45-29 600] ng L-1 ; P = .0007), troponin T levels (63 [22-352] vs. 15 [5-407] ng L-1 ; P = .0002), and the 21-d mortality rate (46% vs. 7%; P < .001) were substantially higher in patients with aPH compared to patients not meeting aPH criteria. CONCLUSION: TTE-defined acute pulmonary hypertension was frequently observed in severely ill Covid-19 patients. Furthermore, aPH was linked to biomarker-defined myocardial injury and cardiac failure, as well as an almost sevenfold increase in 21-d mortality.


Subject(s)
COVID-19/complications , Critical Care , Hypertension, Pulmonary/etiology , SARS-CoV-2 , Acute Disease , Adult , Aged , Biomarkers , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Echocardiography , Female , Fibrin Fibrinogen Degradation Products/analysis , Follow-Up Studies , Heart Failure/blood , Heart Failure/etiology , Heart Failure/mortality , Hospital Mortality , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/epidemiology , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Procedures and Techniques Utilization , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Sweden , Tertiary Care Centers/statistics & numerical data , Treatment Outcome , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/etiology , Troponin T/blood
16.
Crit Pathw Cardiol ; 20(1): 44-52, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1135914

ABSTRACT

Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.


Subject(s)
Arrhythmias, Cardiac/virology , COVID-19/complications , Myocarditis/blood , Myocarditis/virology , SARS-CoV-2/pathogenicity , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/mortality , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/mortality , Cytokines/blood , Hospitalization , Humans , Myocarditis/mortality , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/blood
17.
Int J Infect Dis ; 105: 551-559, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1131382

ABSTRACT

OBJECTIVES: Previous observational studies have suggested that increased cardiac markers are commonly found in COVID-19. This study aimed to determine the relationship between several cardiac markers and the severity/mortality of COVID-19 patients. METHODS: Several cardiac markers were analysed in this meta-analysis. RevMan 5.4 was used to provide pooled estimates for standardised mean difference (SMD) with 95% confidence intervals. RESULTS: Twenty-nine clinical studies were included in this meta-analysis. Significantly higher CK-MB (0.64, 95% CI = 0.19-1.09), PCT (0.47, 95% CI = 0.26-0.68), NT-proBNP (1.90, 95% CI = 1.63-2.17), BNP (1.86, 95% CI = 1.63-2.09), and d-dimer (1.30, 95% CI = 0.91-1.69) were found in severe compared with non-severe COVID-19. Significantly higher CK-MB (3.84, 95% CI = 0.62-7.05), PCT (1.49, 95% CI = 0.86-2.13), NT-proBNP (4.66, 95% CI = 2.42-6.91), BNP (1.96, 95% CI = 0.78-3.14), troponin (1.64 (95% CI = 0.83-2.45), and d-dimer (2.72, 95% CI = 2.14-3.29) were found in those who died from compared with survivors of COVID-19. CONCLUSIONS: High CK-MB, PCT, NT-proBNP, BNP, and d-dimer could be predictive markers for severity of COVID-19, while high CK-MB, PCT, NT-proBNP, BNP, troponin, and d-dimer could be predictive markers for survival of COVID-19 patients.


Subject(s)
COVID-19/mortality , SARS-CoV-2 , Biomarkers , COVID-19/blood , Creatine Kinase, MB Form/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Procalcitonin/blood , Severity of Illness Index
18.
Anal Bioanal Chem ; 413(11): 2971-2984, 2021 May.
Article in English | MEDLINE | ID: covidwho-1126530

ABSTRACT

The kallikrein-kinin system (KKS) is involved in many physiological and pathophysiological processes and is assumed to be connected to the development of clinical symptoms of angioedema or COVID-19, among other diseases. However, despite its diverse role in the regulation of physiological and pathophysiological functions, knowledge about the KKS in vivo remains limited. The short half-lives of kinins, their low abundance and structural similarities and the artificial generation of the kinin bradykinin greatly hinder reliable and accurate determination of kinin levels in plasma. To address these issues, a sensitive LC-MS/MS platform for the comprehensive and simultaneous determination of the four active kinins bradykinin, kallidin, des-Arg(9)-bradykinin and des-Arg(10)-kallidin and their major metabolites bradykinin 2-9, bradykinin 1-7 and bradykinin 1-5 was developed. This platform was validated according to the bioanalytical guideline of the US Food and Drug Administration regarding linearity, accuracy, precision, sensitivity, carry-over, recovery, parallelism, matrix effects and stability in plasma of healthy volunteers. The validated platform encompassed a broad calibration curve range from 2.0-15.3 pg/mL (depending on the kinin) up to 1000 pg/mL, covering the expected concentrations in disease states. No source-dependent matrix effects were identified, and suitable stability of the analytes in plasma was observed. The applicability of the developed platform was proven by the determination of endogenous levels in healthy volunteers, whose plasma kinin levels were successfully detected in the low pg/mL range. The established platform facilitates the investigation of kinin-mediated diseases (e.g. angioedema, COVID-19) and enables the assessment of the impact of altered enzyme activities on the formation or degradation of kinins.


Subject(s)
Bradykinin/analogs & derivatives , Bradykinin/blood , Kallidin/analogs & derivatives , Kallidin/blood , Kallikrein-Kinin System , Tandem Mass Spectrometry/methods , COVID-19/blood , Chromatography, Liquid/methods , Humans , Limit of Detection , Peptide Fragments/blood
19.
Circ Heart Fail ; 14(3): e007048, 2021 03.
Article in English | MEDLINE | ID: covidwho-1119347

ABSTRACT

BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. METHODS: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. RESULTS: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (P=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (P=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (P=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. CONCLUSIONS: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.


Subject(s)
Benzhydryl Compounds/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Glucosides/therapeutic use , Heart Failure/drug therapy , Hospitalization , Kidney/drug effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Stroke Volume/drug effects , Ventricular Function, Left/drug effects , Aged , Aged, 80 and over , Benzhydryl Compounds/adverse effects , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19 , Creatinine/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Early Termination of Clinical Trials , Female , Glucosides/adverse effects , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Japan , Kidney/physiopathology , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prospective Studies , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Time Factors , Treatment Outcome
20.
Sci Rep ; 11(1): 5121, 2021 03 04.
Article in English | MEDLINE | ID: covidwho-1117669

ABSTRACT

Mid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893-11.413], together with increased neutrophil count (OR = 1.029 [1.011-1.049]) and WHO disease severity class (OR = 7.632 [5.871-19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771-0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728-0.987] and a specificity of 0.687 [95% Cl 0.587-0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.


Subject(s)
Adrenomedullin/blood , COVID-19/blood , Peptide Fragments/blood , Protein Precursors/blood , Aged , Biomarkers/blood , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
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