Prediction Value of KREBS Von Den Lungen-6 (KL-6) Biomarker in COVID-19 Patients: A Systematic Review and Meta-Analysis.

The SARS-CoV-2 (COVID-19) pandemic is a major issue that necessitates the use of cutting-edge disease prediction models. The aim of the study was to assess the existing evidence regarding association between Krebs von den Lungen-6 levels and COVID-19 severity. A literature search was performed on Web of Science, PubMed, Scopus and Cochrane Central Register of Controlled Trials databases from 1 January 2020 up to 2 August 2022. The electronic database search was supplemented by searching Google Scholar. In addition, reference lists of relative articles were also reviewed. KL-6 levels among COVID-19 positive vs. negative patients varied and amounted to 443.37 ± 249.33 vs. 205.73 ± 86.8 U/mL (MD = 275.33; 95%CI: 144.57 to 406.09; p < 0.001). The KL-6 level was 402.82 ± 261.16 U/mL in the severe group and was statistically significantly higher than in the non-severe group (297.38 ± 90.46 U/mL; MD = 192.45; 95%CI: 118.19 to 266.72; p < 0.001). The KL-6 level in the mild group was 272.28 ± 95.42 U/mL, compared to 268.04 ± 55.04 U/mL in the moderate COVID-19 group (MD = -12.58; 95%CI: -21.59 to -3.57; p = 0.006). Our meta-analysis indicates a significant association between increased KL-6 levels and SARS-CoV-2 infection. Moreover, KL-6 levels are significantly higher in patients with a more severe course of COVID-19, indicating that KL-6 may be a useful predictor to identify patients at risk for severe COVID-19.

Diagnostic value of lactate dehydrogenase in COVID-19: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis outlines the role of elevated lactate dehydrogenase (LDH) levels in assessing the severity of coronavirus disease 2019 (COVID-19). METHODS: The current study was designed as a systematic review and meta-analysis. Embase, Pub- Med, Web of Science, Scopus and Cochrane Central Register of Controlled Trials were searched to identify the usefulness of LDH as a marker of COVID-19 severity. All extracted data were analyzed using RevMan V.5.4 or STATA V.14 software. RESULTS: A total of 264 records were selected for this meta-analysis. Pooled analysis showed that LDH levels were statistically significantly lower in the group of survivors compared to patients who died in hospital (standardized mean differences [SMD] = -3.10; 95% confidence interval [CI]: -3.40 to -2.79; I2 = 99%; p < 0.001). Lower LDH levels were observed in non-severe groups compared to severe course of COVID-19 (SMD = -2.38; 95% CI: -2.61 to -2.14; I2 = 99%; p < 0.001). The level of LDH was statistically significantly lower in the severe group compared to the critical group (SMD = -1.48; 95% CI: -2.04 to -0.92; I2 = 98%; p < 0.001). Patients who did not require treatment in the intensive care unit (ICU) showed significantly lower levels of LDH compared to patients who required treatment in the ICU (SMD = -3.78; 95% CI: -4.48 to -3.08; I2 = 100%; p < 0.001). CONCLUSIONS: This meta-analysis showed that elevated LDH was associated with a poor outcome in COVID-19.

Arrhythmias in COVID-19/SARS-CoV-2 Pneumonia Infection: Prevalence and Implication for Outcomes.

Arrhythmias (ARs) are potential cardiovascular complication of COVID-19 but may also have a prognostic role. The aim of this study was to explore the prevalence and impact of cardiac ARs in hospitalized COVID-19 patients. All-comer patients admitted to the emergency department of Modena University Hospital from 16 March to 31 December 2020 and diagnosed with COVID-19 pneumonia infection were included in the study. The primary endpoint was 30-day mortality. Out of 902 patients, 637 (70.6%) presented a baseline 12-lead ECG registration; of these, 122 (19.2%) were diagnosed with ARs. Atrial fibrillation (AF, 40.2%) was the most frequent AR detected. The primary endpoint (30-day mortality) occurred in 33.6% (p < 0.001). AR-patients presented an almost 3-fold risk of mortality compared to non-AR-patients at 30d (Adj. OR = 2.8, 95%CI: 1.8-4.3, p < 0.001). After adjustment for significant baseline characteristics selected by a stepwise backward selection, AR-patients remained at increased risk of mortality (Adj. HR = 2.0, 95%CI: 1.9-2.3, p < 0.001). Sub-group analysis revealed that among ARs patients, those with AF at admission presented the highest risk of 30-day mortality (Adj. HR = 3.1, 95%CI: 2.0-4.9, p < 0.001). In conclusion, ARs are a quite common manifestation in COVID-19 patients, who are burdened by even worse prognosis. AR patients with AF presented the highest risk of mortality; thus, these patients may benefit from a more aggressive secondary preventive therapy and a closer follow up.

Effect of Coronary Artery Disease on COVID-19-Prognosis and Risk Assessment: A Systematic Review and Meta-Analysis.

Coronary artery disease (CAD) is the leading cause of death worldwide. Patients with pre-existing CAD were shown to have a more severe course of COVID-19, but this association has not been clarified. We performed a meta-analysis to determine the association between CAD and COVID-19 outcomes. We searched Scopus, Medline (PubMed), Web of Science, Embase, and Cochrane databases up to 2 November 2021. There were 62 studies with a total population of 49,286 patients included in the meta-analysis. CAD occurrence in survivor vs. non-survivor groups varied and amounted to 9.2% vs. 22.9%, respectively (OR = 0.33; 95%CI: 0.29 to 0.39; I2 = 70%; p < 0.001). CAD was also associated with increased severity of COVID-19 disease and was (10.8% vs. 5.6%, respectively, for severe vs. non-severe groups (OR = 2.28; 95%CI: 1.59 to 3.27; I2 = 72%; p < 0.001). The role of history of CAD in mortality and severe condition in COVID-19 presents itself as prominent-although a risk of bias in retrospective trials needs to be assessed, in case of our meta-analysis the statistically significant results when it comes to higher mortality among patients with CAD compared to non-CAD patients, a more severe condition observed in patients with CAD, and a visibly more frequent admission to intensive care unit in patients with CAD, it seems that an incidence of cardiovascular events plays a role in COVID-19 prognosis.

Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size. DESIGN: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg every day; days 4 and 5: 5.0 mg every day) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 hours to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days. CONCLUSION: The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI.

Impact of COVID-19 on in-hospital cardiac arrest outcomes: An updated meta-analysis.

BACKGROUND: The main purposes of this meta-analysis are to update the information about the impact of coronavirus disease 2019 (COVID-19) pandemic on outcomes of in-hospital cardiac arrest (IHCA) and to investigate the impact of being infected by by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) on IHCA outcomes. METHODS: The current meta-analysis is an update and follows the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: In analyses, pre- and intra-COVID-19 periods were observed for: shockable rhythms in 17.6% vs. 16.2% (odds ratio [OR]: 1.11; 95% confidence interval [CI]: 0.71-1.72; p = 0.65), return of spontaneous circulation (ROSC) in 47.4% vs. 44.0% (OR: 1.36; 95% CI: 0.90-2.07; p = 0.15), 30-day mortality in 59.8% vs. 60.9% (OR: 0.95; 95% CI: 0.75-1.22; p = 0.69) and overall mortality 75.8% vs. 74.7% (OR: 0.80; 95% CI: 0.49-1.28; p = 0.35), respectively. In analyses, SARS-CoV-2 positive and negative patients were observed for: shockable rhythms in 9.6% vs. 19.8% (OR: 0.51; 95% CI: 0.35-0.73; p < 0.001), ROSC in 33.9% vs. 52.1% (OR: 0.47; 95% CI: 0.30-0.73; p < 0.001), 30-day mortality in 77.2% vs. 59.7% (OR: 2.08; 95% CI: 1.28-3.38; p = 0.003) and overall mortality in 94.9% vs. 76.7% (OR: 3.20; 95% CI: 0.98-10.49; p = 0.05), respectively. CONCLUSIONS: Despite ROSC, 30-day and overall mortality rate were not statistically different in pre- vs. intra-COVID-19 periods, a lower incidence of ROSC and higher 20-day mortality rate were observed in SARS-CoV-2 (+) compared to SARS-CoV-2 (-) patients.

Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the adult population. Herein, is a systematic review with meta-analysis to determine the impact of AF/atrial flutter (AFL) on mortality, as well as individual complications in patients hospitalized with the coronavirus disease 2019 (COVID-19). METHODS: A systematic search of the SCOPUS, Medline, Web of Science, CINAHL and Cochrane databases was performed. The a priori primary outcome of interest was in-hospital mortality. A random-effects model was used to pool study results. RESULTS: Nineteen studies which included 33,296 patients were involved in this meta-analysis. Inhospital mortality for AF/AFL vs. no-AF/AFL groups varied and amounted to 32.8% vs. 14.2%, respectively (risk ratio [RR]: 2.18; 95% confidence interval [CI]: 1.79-2.65; p < 0.001). In-hospital mortality in new onset AF/AFL compared to no-AFAFL was 22.0% vs. 18.8% (RR: 1.86; 95% CI: 1.54-2.24; p < 0.001). Intensive care unit (ICU) admission was required for 17.7% of patients with AF/AFL compared to 10.8% for patients without AF/AFL (RR: 1.94; 95% CI: 1.04-3.62; p = 0.04). CONCLUSIONS: The present study reveals that AF/AFL is associated with increased in-hospital mortality and worse outcomes in patients with COVID-19 and may be used as a negative prognostic factor in these patients. Patients with AF/AFL are at higher risk of hospitalization in ICU. The presence of AF/AFL in individuals with COVID-19 is associated with higher risk of complications, such as bleeding, acute kidney injury and heart failure. AF/AFL may be associated with unfavorable outcomes due to the hemodynamic compromise of cardiac function itself or hyperinflammatory state typical of these conditions.

Clinical and electrocardiographic characteristics at admission of COVID-19/SARS-CoV2 pneumonia infection.

BACKGROUND: The aim of the present study was to compare clinical and electrocardiographic characteristics of patients with COVID-19 pneumonia in Modena, Emilia Romagna, Italy. METHODS: Patients admitted to the emergency department for suspected COVID-19 pneumonia from March the 16th to April the 15th were enrolled in the study. COVID-19 pneumonia was confirmed by positive nasopharyngeal swab. Primary endpoint was 30-day mortality. RESULTS: 201 patients were diagnosed with COVID-19 pneumonia. Compared to survivors, patients who died were older (79.7 ± 10.8 vs 65.6 ± 14.1, p < 0.001), with a more complex cardiovascular history, including coronary artery disease (CAD, 33.3% vs 13.3%, p = 0.004), atrial fibrillation (23.8 vs 8.8, p = 0.011) and chronic kidney disease (CKD 35.7% vs 7.0%, p < 0.001). 30-day mortality was 20,9% in these patients; atrial fibrillation (OR 12.74, 95% CI 3.65-44.48, p < 0.001), ST-segment depression (OR 5.30, 95% CI 1.50-18.81, p = 0.010) and QTc-interval prolongation (OR 3.17, 95% CI 1.24-8.10, p = 0.016) at ECG admission were associated to an increased mortality risk. On the contrary, sinus rhythm (OR 0.08, 95% CI 0.02-0.27, p < 0.001) and low-molecular weight heparin (LMWH) administration (OR 0.08, 95% CI 0.02-0.29, p < 0.001) were related to reduced mortality. At multivariate analysis, after adjustment for age, sex, diabetes, CAD, and MCA admission, sinus rhythm (HR 2.7, CI 95% 1.1-7.0, p = 0.038) and LMWH (HR 8.5, 95% CI 2.0-36.6, p = 0.004) were confirmed to be independent predictors of increased survival. CONCLUSION: Sinus rhythm at ECG admission in COVID-19 pneumonia patients was associated with greater survival as well as LMWH administration, which conferred an overall better outcome.