Statistics and Management COVID-19 in Kosovo-Case Study Hospital of Ferizaj

Infectious diseases are disorders caused by microorganisms such as bacteria, viruses, parasites or fungi. According to the World Health Organization, infectious diseases cause about 26% of the world's deaths and are the leading cause of death in people younger than 50 years old. Infectious diseases are classified into new infectious diseases, which include SARS-1, SARS-2, bird flu, etc., and recurrent diseases, which include pre-existing infections with known incidence and geographical spread. Coronaviruses are a family of viruses widely found in animals and humans, responsible for a variety of diseases, ranging from common cold to much more severe diseases which often lead to pneumonia. The group of new diseases also includes Coronavirus 2019 (COVID-19), which initially causes a respiratory infection with the continuation of other complications. This virus is a new type of beta-coronavirus, which first appeared in China and later spread very fast all over the world leading to a global pandemic. Disease monitoring should primarily include erythrocyte sedimentation rate, leukocyte count, leukocyte formula, C-reactive protein (CRP), determination of Troponin I (hsTnI) and T (cTnT), pro-B Type N-terminal natriuretic peptide (NT-proBNP), fibrinogen and D-dimer levels. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Statistical Processing of Relationship Between Biomarkers and Disease Severity Caused by COVID-19 Infection-Delta Variant

Severe infectious disease caused by acute respiratory syndrome, COVID-19 (SARS-CoV-2), spread rapidly worldwide, infecting several million people. According to scientific data, the disease develops through several different stages. After 2–4 days of infection and disease development, the lower respiratory tract is attacked and in a relatively short time interstitial pneumonia develops in a certain number of patients (with genetic predisposition between 5 and 10% of cases). Patients infected with COVID-19 have symptoms such as very high temperatures, fever, persistent cough, joint and bone pain, in some cases diarrhea, and loss of appetite and taste. Disease monitoring should primarily include erythrocyte sedimentation rate, leukocyte count, leukocyte count formula, C-reactive protein (CRP), determination of troponin I (hsTnI) and T (cTnT) levels, N-terminal pro-B natriuretic peptide (NT-proBNP), fibrinogen, and D-dimer level. Previous studies have shown that in pneumonia developed from chronic and acute obstructive pulmonary infections, high levels of D-dimer are observed in patients, and it is suggested that this parameter can be used as a specific prognostic biomarker, and the values higher than > 1000 ng/ml represent increased risk factors for mortality in patients with COVID-19. Because vascular thrombosis affects the promotion of an unfavorable clinical progression for the patient, the identification of early and accurate predictors of the worst outcome seems to be essential for timely and appropriate anticoagulant treatment in patients with SARS-CoV-2 infection. Overall, these data suggest that acute myocardial damage, or heart failure, may be an important indicator of disease severity and adverse prognosis in patients with COVID-19. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Cardiac sequelae after COVID-19: Results of a 1-year follow-up study with echocardiography and biomarkers.

Objective: To evaluate the need for cardiac monitoring in unselected patients recovered from COVID-19 and to estimate the risk of heart complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Materials and methods: During March 2020 and January 2021, 106 patients who had recovered from SARS-CoV-2 (alpha and beta variants) were enrolled in prospective observational cohort study CoSuBr (Covid Survivals in Brno). The diagnosis was based on a reverse transcription-polymerase chain reaction swab test of the upper respiratory tract. Demographic parameters, patient history, clinical evaluation, cardiac biomarkers, ECG and echocardiography were recorded during three visits (Visit 1 at least 6 weeks after infection, Visit 2 three months later, and Visit 3 one year after Visit 1). Results: 58.5% of the study group (n = 106) were female, while the mean age was 46 years (range 18-77 years). The mean time interval between the onset of infection and the follow-up visit was 107 days. One quarter (24.5%) of the patients required hospitalization during the acute phase of the disease; the rest recovered at home. 74% suffered a mild form of the disease, with 4.8, 18.1, and 2.9% suffering moderate, severe, and critical forms, respectively. At the time of enrolment, 64.2% of the patients reported persistent symptoms, while more than half of the whole group (50.9%) mentioned at least one symptom of possible cardiac origin (breathing problems, palpitations, exercise intolerance, fatigue). In the 1-year follow-up after COVID-19 infection, left ventricle ejection fraction showed no significant decrease [median (IQR) change was -1.0 (-6.0; 4.0)%, p = 0.150], and there were no changes of troponin (mean change -0.1 ± 1.72 ng/L; p = 0.380) or NT-proBNP [median (IQR) change 2.0 (-20.0; 29.0) pg/mL; p = 0.315]. There was a mild decrease in right ventricle end diastolic diameter (-mean change 2.3 ± 5.61 mm, p < 0.001), while no right ventricle dysfunction was detected. There was very mild progress in left ventricle diastolic diameter [median (IQR) change 1.0 (-1.0; 4.0) mm; p = 0.001] between V1 and V3, mild enlargement of the left atrium (mean change 1.2 ± 4.17 mm; p = 0.021) and a non-significant trend to impairment of left ventricle diastolic dysfunction. There was a mild change in pulmonary artery systolic pressure [median (IQR) change 3.0 (-2.0; 8.0) mmHg; p = 0.038]. Conclusion: Despite a lot of information regarding cardiac impairment due to SARS-CoV2, our study does not suggest an increased risk for developing clinically significant heart changes during the 1-year follow-up. Based on our results, routine echocardiography and biomarkers collection is currently not recommended after COVID-19 recovery.

Age-adjusted NT-proBNP could help in the early identification and follow-up of children at risk for severe multisystem inflammatory syndrome associated with COVID-19 (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) has emerged as a new disease associated with COVID-19 that presents in acute critically ill children with acute cardiovascular dysfunction. AIM: To determine whether the age-adjusted N-terminal pro-brain natriuretic peptide (NT-proBNP) value (Z-log-NT-proBNP) is associated with severe MIS-C and myocardial dysfunction. METHODS: A retrospective study was conducted which included children with MIS-C managed at our institution between April 1, 2020, and February 28, 2022. We divided the population into groups depending on severity based on pediatric intensive care unit (PICU) admission. We compared Z-log-NT-proBNP values across these groups and analyzed Z-log-NT-proBNP dynamics during the one-month follow-up. RESULTS: We included 17 participants [median age 3 (2-9) years] and seven (41%) required PICU admission. All (100%) of these cases presented very high (Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5 (50%) patients with non-severe MIS-C (P = 0.025). NT-proBNP was significantly correlated with high-sensitive Troponin I levels (P = 0.045), Ross modified score (P = 0.003) and left ventricle ejection fraction (P = 0.021). CONCLUSION: Raised NT-proBNP, specifically very high values (Z-log-NT-proBNP > 4) could help in the early identification of MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission.

Right heart condition in patients with COVID-19 pneumonia

Aim. To assess right heart condition in patients with coronavirus disease 2019 (COVID-19) pneumonia. Material and methods. One hundred and five patients with COVID-19 pneumonia were divided into 3 groups depending on the involvement of lung parenchyma: group I — 0-25%, II — 25-50%, III — 50-75%. The clinical status of patients was assessed using the NEWS2 and SHOKS-COVID scales. A complete blood count and biochemical blood tests were performed to determine the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I. Echocardiography was performed to assess the right heart structural, hemodynamic and functional parameters. Results. In patients with COVID-19 pneumonia, with an increase in lung paren-chyma involvement, the intensity of systemic inflammatory response increased: C-reactive protein, group I — (4 [1,9;35] mg/l), in III — (70,5 [33;144] mg/l) (pI-III=0,012);myocardial stress marker level increased: NT-proBNP, group I — 77 [48;150] ng/l, group III — 165 [100;287] ng/l (pI-III =0,047). The dependence of NT-proBNP on C-reactive protein level was revealed (r=0,335, p=0,03). Intergroup comparison did not reveal significant differences between the main right heart functional parameters: TAPSE, Tei index (PW and TDI), FAC of the right ventricle (RV) (p>0,05). However, differences in the tricuspid annular peaks were found as follows: group I — 0,14 [0,12;0,14] m/s, group II — 0,14 [0,12;0,15] m/s, group III — 0,16 [0,14;0,17] m/s (pI-II =0,012, pI-III =0,014) and RV global longitudinal strain: group I — 19,63±7,72%, group III — 27,4±5,93% (pI-III =0,014). The relationship between the RV global longitudinal strain and SHOKS-COVID score was confirmed (r=0,381;p=0,024). Conclusion. Patients with COVID-19 pneumonia showed no signs of right heart dysfunction. The development of RV hyperfunction was noted. Most likely, this is a compensatory mechanism in response to acute RV afterload. NT-proBNP increase under conditions of an inflammatory response may indicate myocardial stress. The results obtained allow to expand our understanding of the right heart condition in patients with COVID-19 pneumonia. © 2021, Silicea-Poligraf. All rights reserved.

Cardiovascular markers and COVID-19.

COVID-19 is an emerging viral disease with incompletely elucidated pathogenesis, a heterogeneous clinical profile, and significant interindividual variability. The major cardiovascular complications of COVID-19 include acute cardiac injury, acute myocardial infarction (AMI), myocarditis, arrhythmia, heart failure, and venous thromboembolism (VTE)/pulmonary embolism (PE). Elevated BNP /NT-proBNP, troponin and d-dimer levels has been found in a significant proportion of patients since the first data analysis, suggesting that myocardial damage is a likely pathogenic mechanism contributing to severe disease and mortality. The level of these markers is now associated with a risk of adverse outcome, namely mortality. The aim of our study is to highlight the importance of these biomarkers for the prediction of cardiovascular complications and their potential role in the evolution of COVID-19.

Prognostic Value of Admission-to-Discharge Change in Integral Congestion Assessment for Predicting Adverse Outcomes in Patients with Decompensated Heart Failure.

This study was performed to evaluate the prognostic value of relative changes from admission to discharge (Δ%) of integrated congestion assessment to predict adverse outcomes in patients with irreversible heart failure (HF) during a one-year follow-up. The study included 122 patients (60% males, median age of 69 years) with decompensated HF. Most of the patients (92%) had a history of arterial hypertension, 53.3% had coronary heart disease, and 40.2% had type 2 diabetes mellitus. All patients underwent assessments, including NT-proBNP, lung ultrasound (LUS) B-line score, liver stiffness by transient elastography, and resistance and reactance by bioimpedance vector analysis (BIVA). The assessments were performed at admission and discharge, and a relative change from admission (delta percentage, Δ%) was calculated. Long-term clinical outcomes were assessed by a structured interview conducted 1, 3, 6, and 12 months after discharge. The cut-offs for the occurrence of the endpoint events were Δ% NT-proBNP of ≥ -25, Δ% liver stiffness of ≥ -44, Δ% B-line score on lung ultrasound of ≥ -73, Δ% BIVA resistance of ≤ 18, and Δ% BIVA reactance of ≤ 40. It was revealed that 55% of endpoint events, including 22 (18%) deaths and 33 (27%) readmissions, occurred within a median of 74 days (interquartile range: 33-147). Patients with an endpoint event had significantly worse values of all studied parameters in contrast to patients without it. There was a significant direct association between Δ% NT-proBNP and Δ% B-lines (r=0.18; P=0.04), and a highly reliable inverse association was observed between Δ% liver stiffness and Δ% BIVA reactance (r=-0.4; P<0.001). No significant associations were found between the other parameters. Univariate Cox regression analysis demonstrated the independent prognostic value of all congestion markers under study (NT-proBNP, LUS B-lines, liver stiffness, and BIVA reactance) for predicting the combined endpoint. Multivariate Cox regression analysis confirmed the independent prognostic value in predicting the risk of endpoint event for the following parameters: NT-proBNP (hazard rate [HR] 2.5, P=0.001), liver stiffness (HR 2.3, P=0.012), LUS B-line score (HR 2.2, P=0.008). However, it did not find any significant prognostic value for BIVA resistance and reactance. The relative admission-to-discharge change in the integral assessment of congestion had a prognostic value for predicting the risk of adverse outcomes (all-cause mortality and readmission rate) in patients with decompensated HF during a one-year follow-up.

The relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and diastolic heart failure in patients with COVID-19

Diastolic dysfunction has been reported in patients with COVID-19. Due to the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of heart failure, this study investigated the relationship between serum NT-proBNP levels and diastolic heart failure in patients with COVID-19. This descriptive-analytical study was performed at Ayatollah Rouhani Hospital in Babol. Fifty-two patients with confirmed COVID-19 diagnosis, who were admitted to the ICU, were included in this study. The primary outcome was about the relationship and predictive role of NT-proBNP and diastolic heart failure in patients with severe SARS-CoV-2 infection. Patients with pro BNP > 125 pg/ml underwent echocardiography, and the relationship between echocardiographic indices and NT-proBNP was assessed as the secondary outcome. Our study showed that plasma NT-proBNP levels in patients with increased diastolic dysfunction were associated with disease severity. It was also found that the cut-off point of NT-proBNP = 799 pg/ml could be a predictor of diastolic dysfunction grades two and three. In this study, patients with a serum NT-proBNP level > 799 had 37 times higher chance of having diastolic dysfunction than those with a serum NT-proBNP < 799. Patients with NT-proBNP > 556 had RV_EA > 2 in echocardiography, indicating increased right-sided filling pressures. Despite the confounding factors in the interpretation of the NT-proBNP level in COVID-19, its level can be used to estimate the presence of high-grade diastolic heart failure on the left side and the right side of the heart and the presence of high filling pressures. Lower levels of NT-proBNP are associated with right-sided diastolic failure.

Impaired Vagal Activity in Long-COVID-19 Patients.

Long-COVID-19 refers to the signs and symptoms that continue or develop after the "acute COVID-19" phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized ß-coefficient = 0.259), NT-ProBNP (standardized ß-coefficient = 0.281), HF component of spectral analysis (standardized ß-coefficient = 0.696), and LF/HF ratio (standardized ß-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.

Plasma Proteomics of COVID-19-Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics.

To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFß signaling, and ADAMTS13, the von Willebrand Factor-cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.

Optimal cut points of N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) in patients with COVID-19.

BACKGROUND: COVID19 patients may suffer from multiple cardiovascular complications. Recently, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) was a potentially independent risk factor for COVID-19 in-hospital death. The present study aimed to find new optimal cut points for NT-proBNP across censored survival failure time outcomes in hospitalized COVID-19 patients. RESULTS: This cohort study was conducted on 272 patients with COVID-19 whose initial records were recorded from March 2020 to July 2020. Demographic characteristics, clinical examinations, and laboratory measurements were collected at the beginning of the admission registered in the patient record system located in the hospital. We used the maximally selected rank statistics to determine the optimal cut points for NT-proBNP (the most significant split based on the standardized log-rank test). Survival time was defined as the days from hospital admission to discharge day. In this cohort study, two optimal cut points for NT-proBNP were 331 (pg/mL) and 11,126 (pg/mL) based on a survival model. The adjusted HR of NT-proBNP for in-hospital death was 3.41 (95% CI: 1.22-9.51, P = 0.02) for medium against low category, and 3.84 (95% CI: 1.30-11.57, P = 0.01) for high in comparison with low group. CONCLUSIONS: We reported a dramatically increased concentration of NT-proBNP among COVID-19 patients without heart failure in both severe and non-severe cases. Moreover, our study showed that a high level of NT-proBNP was highly associated with the prolonged survival time of patients with COVID-19. NT-proBNP is a strong prognostic indicator of in-hospital death in the second week of admission.

Prognostic value of biochemical parameters among severe COVID-19 patients admitted to an intensive care unit of a tertiary hospital in South Africa.

Background: Data on biochemical markers and their association with mortality rates in patients with severe coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) in sub-Saharan Africa are scarce. An evaluation of baseline routine biochemical parameters was performed in COVID-19 patients admitted to the ICU, in order to identify prognostic biomarkers. Methods: Demographic, clinical, and laboratory data were collected prospectively from patients with PCR-confirmed COVID-19 admitted to the adult ICU of a tertiary hospital in Cape Town, South Africa, between October 2020 and February 2021. Robust Poisson regression methods and the receiver operating characteristic (ROC) curve were used to explore the association of biochemical parameters with severity and mortality. Results: A total of 82 patients (median age 53.8 years, interquartile range 46.4-59.7 years) were enrolled, of whom 55 (67%) were female and 27 (33%) were male. The median duration of ICU stay was 10 days (interquartile range 5-14 days); 54/82 patients died (66% case fatality rate). Baseline lactate dehydrogenase (LDH) (adjusted relative risk 1.002, 95% confidence interval 1.0004-1.004; P = 0.016) and N-terminal pro B-type natriuretic peptide (NT-proBNP) (adjusted relative risk 1.0004, 95% confidence interval 1.0001-1.0007; P = 0.014) were both found to be independent risk factors of a poor prognosis, with optimal cut-off values of 449.5 U/l (sensitivity 100%, specificity 43%) and 551 pg/ml (sensitivity 49%, specificity 86%), respectively. Conclusions: LDH and NT-proBNP appear to be promising predictors of a poor prognosis in COVID-19 patients in the ICU. Studies with a larger sample size are required to confirm the validity of this combination of biomarkers.

Clinically suspected myocarditis in COVID-19 patients: Case series and review of the literature.

This Study describes eleven patients positive for severe acute respiratory syndrome coronavirus 2. In our cases, females and younger patients developed more severe disease. In contrast, improvement in left ventricular ejection fraction and N-terminal prohormone brain natriuretic peptide within the first week of treatment contributed to promising outcomes.

Relationships between NT-proBNP and novel biochemical parameters and increased cardiovascular risk in COVID-19 NT-proBNP levels and novel inflammatory biomarkers in COVID-19

Aim: The ongoing pandemic of coronavirus disease 2019 (COVID-19) infection has been declared a global emergency. Although most people have had mad illness due to this infection, some patients are seriously affected with complications particularly involving the respiratory and cardiovascular systems. Although respiratory system involvement is in the foreground, cardiovascular complications result in worse clinical outcomes. The aim of this study is to compare the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios, which are accepted as markers of negative outcomes in cases of cardiovascular diseases, of patients with COVID-19 and healthy subjects and reveal the increased risk of cardiovascular disease in patients with COVID-19. Material and Methods: This prospective study was designed In a single center and included 33 patients with COVID-19 (Group 1) and 33 healthy subjects selected from among healthcare professionals (Group 2). The NT-proBNP levels and neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and platelet-tolymphocyte ratios were compared between the groups. Results: NT-proBNP levels, neutrophil-to-lymphocyte ratios, and platelet-to-lymphocyte ratios were statistically significantly higher in the patients with COVID-19 (p<0.0001) and lymphocyte-to-monocyte ratios were statistically significantly lower in the same group (p<0.0001). Discussion: Cardiovascular manifestations result in worse outcomes in patients with COVID-19 even though the disease primarily affects the respiratory system. Early detection of this clinical situation and the taking of precautions have vital importance in the progress of the disease. The NT-proBNP level and neutrophil-to-lymphocyte, lymphocyte-to-monocyte, and platelet-to-lymphocyte ratios are inexpensive, easy, fast, and reproducible parameters that can be used in the determination of probable cardiovascular events that may develop during COVID-19 and enable early optimal treatment strategies for patients.

Normalized Cardiac Structure and Function in COVID-19 Survivors Late After Recovery.

Background: Coronavirus disease 2019 can result in myocardial injury in the acute phase. However, information on the late cardiac consequences of coronavirus disease 2019 (COVID-19) is limited. Methods: We conducted a prospective observational cohort study to investigate the late cardiac consequences of COVID-19. Standard echocardiography and myocardial strain assessment were performed, and cardiac blood biomarkers were tested in 86 COVID-19 survivors 327 days (IQR 318-337 days) after recovery. Comparisons were made with 28 age-matched and sex-matched healthy controls and 30 risk factor-matched patients. Results: There were no significant differences in all echocardiographic structural and functional parameters, including left ventricular (LV) global longitudinal strain, right ventricular (RV) longitudinal strain, LV end-diastolic volume, RV dimension, and the ratio of peak early velocity in mitral inflow to peak early diastolic velocity in the septal mitral annulus (E/e') among COVID-19 survivors, healthy controls and risk factor-matched controls. Even 26 patients with myocardial injury at admission did not have any echocardiographic structural and functional abnormalities. There were no significant differences among the three groups with respect to serum concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI). Conclusion: This study showed that COVID-19 survivors, including those with myocardial injury at admission and those with severe and critical types of illness, do not have any echocardiographic evidence of cardiac structural and functional abnormalities 327 days after diagnosis.

Heart Failure Probability and Early Outcomes of Critically Ill Patients With COVID-19: A Prospective, Multicenter Study.

Background: The relationship between cardiac functions and the fatal outcome of coronavirus disease 2019 (COVID-19) is still largely underestimated. We aim to explore the role of heart failure (HF) and NT-proBNP in the prognosis of critically ill patients with COVID-19 and construct an easy-to-use predictive model using machine learning. Methods: In this multicenter and prospective study, a total of 1,050 patients with clinical suspicion of COVID-19 were consecutively screened. Finally, 402 laboratory-confirmed critically ill patients with COVID-19 were enrolled. A "triple cut-point" strategy of NT-proBNP was applied to assess the probability of HF. The primary outcome was 30-day all-cause in-hospital death. Prognostic risk factors were analyzed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression, further formulating a nomogram to predict mortality. Results: Within a 30-day follow-up, 27.4% of the 402 patients died. The mortality rate of patients with HF likely was significantly higher than that of the patient with gray zone and HF unlikely (40.8% vs. 25 and 16.5%, respectively, P < 0.001). HF likely [Odds ratio (OR) 1.97, 95% CI 1.13-3.42], age (OR 1.04, 95% CI 1.02-1.06), lymphocyte (OR 0.36, 95% CI 0.19-0.68), albumin (OR 0.92, 95% CI 0.87-0.96), and total bilirubin (OR 1.02, 95% CI 1-1.04) were independently associated with the prognosis of critically ill patients with COVID-19. Moreover, a nomogram was developed by bootstrap validation, and C-index was 0.8 (95% CI 0.74-0.86). Conclusions: This study established a novel nomogram to predict the 30-day all-cause mortality of critically ill patients with COVID-19, highlighting the predominant role of the "triple cut-point" strategy of NT-proBNP, which could assist in risk stratification and improve clinical sequelae.

N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for the Severity and Outcomes With COVID-19 in a Nationwide Hospitalized Cohort.

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.

The Prognostic Value of Cardiac Biomarkers and Echocardiography in Critical COVID-19.

Background: Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores. Methods: Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 h of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index. Results: A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value < 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value = 0.011) were significantly associated with mortality, while other biomarkers (D-dimer, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7). Conclusion: Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.

A comparative study of IL-6, CRP and NT-proBNP levels in post-COVID multisystem inflammatory syndrome in children (MISC) and Kawasaki disease patients.

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.

Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management.

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.