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1.
Int J Obes (Lond) ; 46(10): 1801-1807, 2022 10.
Article in English | MEDLINE | ID: covidwho-1937412

ABSTRACT

BACKGROUND/OBJECTIVES: Patients affected by obesity and Coronavirus disease 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have a higher risk for intensive care (ICU) admission. A state of low-grade chronic inflammation in obesity has been suggested as one of the underlying mechanisms. We investigated whether obesity is associated with differences in new inflammatory biomarkers mid-regional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and clinical outcomes in critically ill patients with SARS-CoV-2 pneumonia. SUBJECTS/METHODS: A total of 105 critically ill patients with SARS-CoV-2 pneumonia were divided in patients with obesity (body mass index (BMI) ≥ 30 kg/m2, n = 42) and patients without obesity (BMI < 30 kg/m2, n = 63) and studied in a retrospective observational cohort study. MR-proADM, CT-proET-1 concentrations, and conventional markers of white blood count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were collected during the first 7 days. RESULTS: BMI was 33.5 (32-36.1) and 26.2 (24.7-27.8) kg/m2 in the group with and without obesity. There were no significant differences in concentrations MR-proADM, CT-proET-1, WBC, CRP, and PCT at baseline and the next 6 days between patients with and without obesity. Only MR-proADM changed significantly over time (p = 0.039). Also, BMI did not correlate with inflammatory biomarkers (MR-proADM rho = 0.150, p = 0.125, CT-proET-1 rho = 0.179, p = 0.067, WBC rho = -0.044, p = 0.654, CRP rho = 0.057, p = 0.564, PCT rho = 0.022, p = 0.842). Finally, no significant differences in time on a ventilator, ICU length of stay, and 28-day mortality between patients with or without obesity were observed. CONCLUSIONS: In critically ill patients with confirmed SARS-CoV-2 pneumonia, obesity was not associated with differences in MR-proADM, and CT-proET-1, or impaired outcome. TRIAL REGISTRATION: Netherlands Trial Register, NL8460.


Subject(s)
Adrenomedullin , COVID-19 , Endothelin-1 , Obesity , Peptide Fragments , Protein Precursors , SARS-CoV-2 , Adrenomedullin/blood , Biomarkers/blood , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/diagnosis , Critical Care , Critical Illness , Disease Progression , Endothelin-1/blood , Humans , Obesity/complications , Patient Admission , Peptide Fragments/blood , Procalcitonin/blood , Prognosis , Protein Precursors/blood , Retrospective Studies
2.
J Pharmacol Sci ; 150(1): 21-30, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1885947

ABSTRACT

The prognosis of patients with severe cases of COVID-19 is poor; thus, biomarkers for earlier prediction of COVID-19 progression are vital. We measured levels of five lung injury-related biomarkers, SP-D, KL-6, presepsin, kallistatin and stratifin, in serum samples collected serially during hospitalization from 31 patients with mild/moderate or severe/critical COVID-19 pneumonia, and their predictive performances were compared. Like the previously reported presepsin, a new biomarker candidate, stratifin, was significantly elevated with the onset of severe or critical symptoms in COVID-19 patients and decreased with symptom improvement. Notably, changes in stratifin and presepsin levels were distinctly earlier than those in SP-D, KL-6 and even SpO2/FiO2 values. Furthermore, serum levels of these biomarkers were significantly higher at the pre-severe stage (before the start of oxygen support) of patients who eventually advanced to severe/critical stages than in the patients who remained at the mild/moderate stage. These results were confirmed in an independent cohort, including 71 mild/moderate and 14 severe/critical patients, for whom the performance of stratifin and presepsin in discriminating between mild/moderate and pre-severe conditions of COVID-19 patients was superior to that of the SpO2/FiO2 ratio. Therefore, we concluded that stratifin and presepsin could be used as prognostic biomarkers for severe COVID-19 progression.


Subject(s)
COVID-19 , Lipopolysaccharide Receptors , 14-3-3 Proteins/blood , Biomarkers , COVID-19/diagnosis , Disease Progression , Exoribonucleases/blood , Humans , Lipopolysaccharide Receptors/blood , Peptide Fragments/blood , Pulmonary Surfactant-Associated Protein D
3.
Hipertens Riesgo Vasc ; 39(3): 105-113, 2022.
Article in Spanish | MEDLINE | ID: covidwho-1859575

ABSTRACT

INTRODUCTION: Cardiovascular compromise in coronavirus disease 2019 (COVID-19) does not necessarily present with the classic symptoms described in myocarditis. There is growing evidence demonstrating subclinical cardiovascular compromise in the context of the intense inflammation unleashed, the cytokine storm involved, the baseline prothrombotic state, and the consequent endothelial dysfunction. We set out to analyse whether Troponin-T (TT) and the amino-terminal fraction of pro-brain natriuretic peptide (NT-proBNP) determined at hospital admission, are related to mortality during the hospitalization of these patients. MATERIAL AND METHODS: Analytical, observational, retrospective cohort and cross-sectional study. It included subjects with COVID-19 hospitalized for moderate-severe illness, from 20/03/20 to 15/11/20. The TT and NT-proBNP obtained in the first 24 hours from admission were analysed. Altered TT was considered if ≥.014 ng/dl and altered NT-proBNP if ≥300 pg/ml. RESULTS: One hundred and eight subjects were included, 63.2% men, age 51.5 years (59-43), 28% were admitted to the Critical Unit and 25% died. The group with elevated TT presented higher mortality (OR = 3.1; 95%CI = 1.10-8.85; p = .02). The group with elevated NT-proBNP also show higher mortality (OR = 3.47; 95%CI = 1.21-9.97; p = .01). On multivariate analysis, only NT-proBNP ≥300 pg/ml remained an independent risk factor. CONCLUSIONS: NT-proBNP levels ≥300 pg/ml at admission in patients with moderate-severe COVID-19 were associated with higher mortality.


Subject(s)
COVID-19 , Natriuretic Peptide, Brain , Peptide Fragments , Troponin T , Biomarkers/blood , Brain , COVID-19/mortality , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , Retrospective Studies , Troponin T/blood
4.
Am J Cardiol ; 167: 125-132, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1633476

ABSTRACT

Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs' cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19.


Subject(s)
COVID-19/blood , Hospital Mortality , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin I/blood , Troponin T/blood , Aged , Aged, 80 and over , COVID-19/mortality , Female , Heart Failure/blood , Humans , Italy , Male , Middle Aged , Prognosis , Proportional Hazards Models , Risk Assessment , SARS-CoV-2
5.
Endocr Metab Immune Disord Drug Targets ; 21(6): 980-993, 2021.
Article in English | MEDLINE | ID: covidwho-1613453

ABSTRACT

Biomarkers are increasingly recognized to have significant clinical value in early identification and progression of various cardiovascular diseases. There are many heart conditions, such as congestive heart failure (CHF), ischemic heart diseases (IHD), and diabetic cardiomyopathy (DCM), and cardiac remodeling, in which the severity of the cardiac pathology can be mirrored through these cardiac biomarkers. From the emergency department (ED) evaluation of acute coronary syndromes (ACS) or suspected acute myocardial infarction (AMI) with cardiac marker Troponin to the diagnosis of chronic conditions like Heart Failure (HF) with natriuretic peptides, like B-type natriuretic peptide (BNP), N-terminal pro-B- type natriuretic peptide (Nt-proBNP) and mid regional pro-atrial natriuretic peptide (MR- proANP), their use is continuously increasing. Their clinical importance has led to the discovery of newer biomarkers, such as the soluble source of tumorigenicity 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), and various micro ribonucleic acids (miRNAs). Since cardiac pathophysiology involves a complex interplay between inflammatory, genetic, neurohormonal, and biochemical levels, these biomarkers could be enzymes, hormones, and biologic substances showing cardiac injury, stress, and malfunction. Therefore, multi-marker approaches with different combinations of novel cardiac biomarkers, and continual assessment of cardiac biomarkers are likely to improve cardiac risk prediction, stratification, and overall patient wellbeing. On the other hand, these biomarkers may reflect coexisting or isolated disease processes in different organ systems other than the cardiovascular system. Therefore, knowledge of cardiac biomarkers is imperative. In this article, we have reviewed the role of cardiac biomarkers and their use in the diagnosis and prognosis of various cardiovascular diseases from different investigations conducted in recent years.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Heart Diseases/blood , Heart Diseases/diagnosis , Animals , Biomarkers/blood , COVID-19/epidemiology , Heart Diseases/epidemiology , Humans , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Troponin T/blood
6.
J Am Heart Assoc ; 10(24): e022913, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1566423

ABSTRACT

Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P<0.001) and shorter median time to death (7 versus 9 days; P<0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P<0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest (P<0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.


Subject(s)
COVID-19 , Heart Failure , Hospital Mortality , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Biomarkers/blood , COVID-19/diagnosis , COVID-19/mortality , Heart Failure/diagnosis , Humans , Prognosis , Prospective Studies
7.
J Cell Mol Med ; 26(2): 274-286, 2022 01.
Article in English | MEDLINE | ID: covidwho-1566302

ABSTRACT

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.


Subject(s)
COVID-19/blood , Cardiovascular Diseases/blood , Cardiovascular System/metabolism , SARS-CoV-2/pathogenicity , Biomarkers/blood , COVID-19/complications , COVID-19/diagnosis , COVID-19/immunology , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/immunology , Cardiovascular System/pathology , Cardiovascular System/virology , Chemokine CCL2/blood , Creatine Kinase, MB Form/blood , Fibrin Fibrinogen Degradation Products/metabolism , Homocysteine/blood , Humans , Interferon-gamma/blood , Interleukin-6/blood , L-Lactate Dehydrogenase/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , Troponin I/blood , Troponin T/blood , Tumor Necrosis Factor-alpha/blood
8.
Hypertension ; 79(2): 365-378, 2022 02.
Article in English | MEDLINE | ID: covidwho-1541968

ABSTRACT

ACE (angiotensin-converting enzyme)-2 as the target for SARS-CoV-2 also negatively regulates the renin-angiotensin system. Pathological activation of ADAM17 (A disintegrin and metalloproteinase-17) may potentiate inflammation and diminish ACE2-mediated tissue protection through proteolytic shedding, contributing to SARS-CoV-2 pathogenesis. We aim to examine plasma soluble ACE2 and angiotensin profiles in relation to outcomes by enrolling consecutive patients admitted for COVID-19 with baseline blood collection at admission and repeated sampling at 7 days. The primary outcome was 90-day mortality, and secondary outcomes were the incidence of end-organ injuries. Overall, 242 patients were included, the median age was 63 (52-74) years, 155 (64.0%) were men, and 57 (23.6%) patients reached the primary end point. Baseline soluble ACE2 was elevated in COVID-19 but was not associated with disease severity or mortality. In contrast, an upward trajectory of soluble ACE2 at repeat sampling was independently associated with an elevated risk of mortality and incidence of acute myocardial injury and circulatory shock. Similarly, an increase in soluble tumor necrosis factor receptor levels was also associated with adverse outcomes. Plasma Ang I, Ang 1-7 (angiotensin 1-7) levels, and the Ang 1-7/Ang II (angiotensin II) ratio were elevated during SARS-CoV-2 infection related to downregulation of ACE activity at baseline. Moreover, patients having an upward trajectory of soluble ACE2 were characterized by an imbalance in the Ang 1-7/Ang II ratio. The observed dysregulation of ACE2 and angiotensin peptides with disease progression suggest a potential role of ADAM17 inhibition and enhancing the beneficial Ang 1-7/Mas axis to improve outcomes against SARS-CoV-2 infection.


Subject(s)
Angiotensin II/blood , Angiotensin I/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , Peptide Fragments/blood , Renin-Angiotensin System/physiology , SARS-CoV-2 , ADAM17 Protein/blood , Aged , COVID-19/mortality , COVID-19/therapy , Enzyme Activation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type II/blood , Respiration, Artificial , Risk , Treatment Outcome
9.
Int J Rheum Dis ; 25(1): 27-31, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1505985

ABSTRACT

BACKGROUND: Post-COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C-reactive protein (CRP), interleukin 6 (IL6) as well as N-terminal probrain natriuretic peptide (NT-proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. METHODOLOGY: This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017-June 2018), with 71 MISC patients over a period of 6 months (July 2020-December 2020). The non-parametric Mann-Whitney U test was used to test for similarity in distributions of the samples of CRP, NT-proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT-proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P < .05 for both cases) than that in MISC (9141.16 pg/mL and 145.66 mg/L respectively). ROC analysis showed NT-proBNP has the best sensitivity and specificity in predicting MISC. CONCLUSION: NT-proBNP and CRP are significantly higher among MISC patients; ROC analysis shows levels >935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.


Subject(s)
C-Reactive Protein/analysis , COVID-19/complications , Interleukin-6/blood , Mucocutaneous Lymph Node Syndrome/blood , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Systemic Inflammatory Response Syndrome/blood , Biomarkers/blood , COVID-19/blood , Child , Child, Preschool , Humans , India , Infant , ROC Curve , SARS-CoV-2
10.
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
11.
JAMA Cardiol ; 7(1): 17-25, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1499191

ABSTRACT

Importance: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. Objective: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Intervention: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. Main Outcomes and Measures: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Results: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. Conclusions and Relevance: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. Trial Registration: ClinicalTrials.gov Identifier: NCT02816736.


Subject(s)
Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Biphenyl Compounds/therapeutic use , Heart Failure/drug therapy , Valsartan/therapeutic use , Biomarkers/blood , Double-Blind Method , Drug Combinations , Female , Heart Failure/blood , Humans , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Stroke Volume
12.
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
14.
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
15.
Am J Emerg Med ; 52: 271.e1-271.e3, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1372852

ABSTRACT

Myocardial infarctions (MI) have been reported in adults with COVID-19. Although MIs are rare in children with COVID-19, cardiac involvement is still possible. In this case report, we present an adolescent with recent COVID-19 infection who presented with an ECG initially suggestive of myocardial infarction (MI). We describe how to differentiate between myocardial infarctions and myopericarditis. A 15-year-old boy, with a history of COVID-19 infection a month prior, presented to the emergency department with fever, abdominal pain, diarrhea, and chest pain. On ECG, he was found to have focal ST-segment elevations in V3 through V6. Given the immediate concern for MI, an emergent echocardiogram was done and showed normal left ventricular systolic function with no regional dyskinesia and normal coronary artery diameters. A repeat ECG showed diffuse ST elevations in the inferior leads and T-wave inversions on V5 and V6, confirming the diagnosis of myopericarditis. In conclusion, multisystem-inflammatory syndrome in children associated with COVID-19 (MIS-C) is a new entity describing a post-infectious inflammatory response in children with prior COVID-19 exposure. Cardiac involvement can include myopericarditis. Initial ECGs may show ST-changes suggestive of MI. However, serial ECGs and echocardiograms can differentiate between MI and myocarditis/myopericarditis. Even with COVID-19, MIs are extremely rare in children, and it is important to be aware of MIS-C and its cardiac complications.


Subject(s)
COVID-19/complications , Emergency Service, Hospital , Pericarditis/diagnosis , ST Elevation Myocardial Infarction/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adolescent , Biomarkers/blood , COVID-19/diagnosis , Diagnosis, Differential , Echocardiography , Electrocardiography , Humans , Male , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , SARS-CoV-2 , Troponin I/blood
16.
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
17.
STAR Protoc ; 2(3): 100707, 2021 09 17.
Article in English | MEDLINE | ID: covidwho-1307268

ABSTRACT

Host humoral immunological response plays an essential role in protection against pathogens. Identification of B-cell epitopes on antigens is required for accurate diagnosis and vaccine development. To map SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) spike linear epitopes, we developed a protocol of profiling sera from patients with COVID-19 (coronavirus disease 2019) via a peptide microarray designed according to spike protein. The protocol is also applicable for other antigens or sample types. This protocol is rapid, high throughput, and the cost is acceptable while it needs specialized microarray facilities. For complete details on the use and execution of this protocol, please refer to Li et al. (2020, 2021a, 2021b).


Subject(s)
Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19/immunology , Epitopes, B-Lymphocyte/immunology , Peptide Fragments/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/blood , COVID-19/virology , Humans , Peptide Fragments/blood , Spike Glycoprotein, Coronavirus/blood
18.
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
19.
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
20.
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
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