Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period.

Purpose: To investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period. Methods: All consecutive hospitalized laboratory-confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality. Results: 74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%. Conclusions: High comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.

A Case of Acute Pericarditis After COVID-19 Vaccination.

A two-dose regimen of Pfizer-BioNTech COVID-19 vaccination confers 95% protection against COronaVIrus Disease 19 (COVID-19) and the safety profile is adequate. To the submission date, there were no reports in literature of acute pericarditis after BNT162b2 vaccination. However, pericarditis has been reported as a rare event associated with COVID-19 infection, which could be due to the pro-inflammatory effects of the spike protein. Recent evidence of post-vaccine myocarditis has been published. Herein we describe the case of a middle-aged healthy women who developed symptoms and signs of acute pericarditis 7-10 days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Although a direct effect cannot be stated, it is important to report a potential adverse vaccine reaction effect that could be associated with the expression of SARS-CoV-2 spike protein induced from the mRNA of the vaccine.

COVID-19 in Elderly Patients Surgically Treated for Lower Limbs Fracture.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic outbreak has posed new problems in the context of patients suffering from other diseases. In particular, musculoskeletal sequelae related to the state of debilitation associated with COVID-19 are important to consider in elderly patients undergoing surgery after lower limbs fracture, especially in the post-operative period. The objective of this study was to evaluate whether COVID-19 influenced biochemical parameter, recovery and mortality of surgically treated patients suffering from lower extremity fractures. METHODS: Laboratory and clinical data of 30 patients were extrapolated and analyzed in the pre-operative and post-operative periods. Among these patients, 13 had COVID-19 infection (COVID-19 +), whereas 17 had no signs of COVID-19 infections (COVID-19 -). Long-term clinical and functional outcomes were also analyzed. RESULTS: Lower calcium, slightly higher values of CRP and much higher values of CPK and AST were observed pre-operatively in COVID-19 + patients, who also showed higher prevalence of long-term sequelae than COVID-19 - patients. CONCLUSIONS: COVID-19 affects long-term outcome of elderly patients with lower limb fractures in a multifactorial way. First, the virus directly damages the muscle tissue. Secondly, the lung function impairment worsens the overall performance, making rehabilitation more challenging.

Preliminary Evidence for IL-10-Induced ACE2 mRNA Expression in Lung-Derived and Endothelial Cells: Implications for SARS-Cov-2 ARDS Pathogenesis.

Angiotensin-converting enzyme 2 (ACE2) is a receptor for the spike protein of SARS-COV-2 that allows viral binding and entry and is expressed on the surface of several pulmonary and non-pulmonary cell types, with induction of a "cytokine storm" upon binding. Other cell types present the receptor and can be infected, including cardiac, renal, intestinal, and endothelial cells. High ACE2 levels protect from inflammation. Despite the relevance of ACE2 levels in COVID-19 pathogenesis, experimental studies to comprehensively address the question of ACE2 regulations are still limited. A relevant observation from the clinic is that, besides the pro-inflammatory cytokines, such as IL-6 and IL-1ß, the anti-inflammatory cytokine IL-10 is also elevated in worse prognosis patients. This could represent somehow a "danger signal", an alarmin from the host organism, given the immuno-regulatory properties of the cytokine. Here, we investigated whether IL-10 could increase ACE2 expression in the lung-derived Calu-3 cell line. We provided preliminary evidence of ACE2 mRNA increase in cells of lung origin in vitro, following IL-10 treatment. Endothelial cell infection by SARS-COV-2 is associated with vasculitis, thromboembolism, and disseminated intravascular coagulation. We confirmed ACE2 expression enhancement by IL-10 treatment also on endothelial cells. The sartans (olmesartan and losartan) showed non-statistically significant ACE2 modulation in Calu-3 and endothelial cells, as compared to untreated control cells. We observed that the antidiabetic biguanide metformin, a putative anti-inflammatory agent, also upregulates ACE2 expression in Calu-3 and endothelial cells. We hypothesized that IL-10 could be a danger signal, and its elevation could possibly represent a feedback mechanism fighting inflammation. Although further confirmatory studies are required, inducing IL-10 upregulation could be clinically relevant in COVID-19-associated acute respiratory distress syndrome (ARDS) and vasculitis, by reinforcing ACE2 levels.

Mechanical concordance between left atrium and left atrial appendage in nonvalvular atrial fibrillation: can it be exploited to avoid transesophageal echocardiography prior to electrical cardioversion during Covid-19 pandemic?

Transesophageal echocardiography (TEE) is the gold standard for assessing left atrial appendage (LAA) mechanic and thrombosis (LAAT); however, TEE is a high-risk procedure for viral transmission during coronavirus disease 2019 (COVID-19) pandemic. We investigated whether deformation indices of left atrium (LA) at transthoracic echocardiography (TTE) correlate with those of LAA assessed by TEE in nonvalvular atrial fibrillation (NVAF) patients undergoing electrical cardioversion (ECV). Consecutive patients with NVAF of ≥ 48 h or unknown duration, who underwent TEE and TTE at our Institution before ECV were retrospectively investigated. Standard echo-Doppler and LA and LAA myocardial strain and strain rate parameters were analyzed. A total of 115 NVAF patients (71.3 ± 8.1 yr/o, 59.1% men) were included: LAAT was diagnosed in 25 (21.7%) patients. Compared to patients without LAAT, those with LAAT had significantly higher CHA2DS2-VASc Risk score (4.5 ± 1.4 vs. 3.5 ± 1.1, p < 0.001), and lower ejection fraction (46.0 ± 14.8 vs. 57.6 ± 8.6%, p < 0.001). In LAAT patients, global strain of LA (8.7 ± 2.6 vs. 16.3 ± 4.5%, p < 0.001) and LAA (7.0 ± 1.7 vs. 11.7 ± 2.0%, p < 0.001) was significantly reduced compared to non-LAAT patients. A close relationship between left atrial strain reservoir (LASr) and LAA-global strain was demonstrated (r = 0.81). By univariable analysis, CHA2DS2-VASc Risk Score (OR 2.01, 95%CI 1.34-3.00), NT-proBNP (OR 1.36, 95%CI 1.19-1.54), ejection fraction (OR 0.92, 95%CI 0.88-0.96), E/e' ratio (OR 2.07, 95%CI 1.51-2.85), and LASr (OR 0.39, 95%CI 0.25-0.62) were strongly associated with LAAT presence at TEE. By multivariable analysis, only LASr (OR 0.40, 95%CI 0.24-0.70) retained statistical significance. ROC curve analysis revealed that an LASr cut-off value ≤ 9.3% had 98.9% sensibility and 100% specificity to identify LAAT by TEE (AUC = 0.98). In patients with NVAF of ≥ 48 h or unknown duration, scheduled to undergo ECV, LA deformation assessment by TTE might substitute invasive measurement of LAA function by TEE, simplifying diagnostic approach and possibly contributing to reduce COVID-19 infection diffusion.

Case Report: An Unusual Case of Biventricular Thrombosis in a COVID-19 Patient With Ischemic Dilated Cardiomyopathy: Assessment of Mass Mobility and Embolic Risk by Tissue Doppler Imaging.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds to angiotensin-converting enzyme 2 (ACE2) receptor on vascular cells. As a consequence, patients with COVID-19 have an increased incidence of thromboembolic complications of the SARS-CoV-2 infection and subsequent endothelial cell damage with consequence of development of systemic vasculitis and diffuse intravascular coagulation. The present case describes a COVID-19 female patient with ischemic dilated cardiomyopathy, who presented with congestive heart failure and echocardiographic evidence of biventricular apical thrombi. The peak antegrade longitudinal velocity (Va) of each thrombotic mass was measured by pulsed wave tissue Doppler imaging (PW-TDI). Both left ventricular and right ventricular apical thrombi were found with a TDI-derived mass peak Va < 10 cm/s. There was no clinical evidence of neither systemic nor pulmonary embolization, probably due to the hypomobility of both left and right ventricular masses.

Long-Term Coronavirus Disease 2019 Complications in Inpatients and Outpatients: A One-Year Follow-up Cohort Study.

BACKGROUND: As the coronavirus pandemic spreads, more and more people are infected with severe acute respiratory syndrome coronavirus 2. The short- and medium-term effects of the infection have been described, but the description of the long-term sequelae is lacking in the literature. METHODS: Patients healed from coronavirus disease 2019 (COVID-19) from February 2020 to May 2020 were considered for inclusion in this study, regardless of the severity of the disease during the acute phase. Eligible patients were consecutively contacted and a semistructured interview was administered between February and March 2021 by trained medical staff. RESULTS: Three hundred three patients were eligible and accepted to participate in the study and were enrolled. Of those surveyed, most patients (81%) reported at least 1 symptom, and the most prevalent symptoms were fatigue (52%), pain (48%), and sleep disorders (47%). Sensory alterations were present in 28% of surveyed patients, but in most of these cases (74% of those affected by sensory alterations or 20% of the overall sample) symptoms reported were either anosmia or dysgeusia. Higher prevalence was generally observed with increasing age, although the most relevant differences were observed when comparing young versus middle-aged adults. CONCLUSIONS: At 12 months after acute infection, COVID-19 survivors were still suffering from symptoms identified at shorter follow-up, and the most frequent symptoms included fatigue, pain, and sleep disorders. A more severe impairment in the acute phase did not seem to predict more severe complications.

Effect of the COVID-19 Outbreak on Pediatric Patients' Admissions to the Emergency Department in an Italian Orthopedic Trauma Hub.

BACKGROUND: The rapid diffusion of Coronavirus disease (COVID-19) in Northern Italy led the Italian government to dictate a national lockdown from 12 March 2020 to 5 May 2020. The aim of this observational cohort study is to analyze the differences in the number of pediatric patients' admission to the Emergency Room (ER) and in the type and causes of injury. METHODS: The pediatric population during the pandemic was compared to a similar group of patients admitted to the ER in 2019. Sex, age, triage color-code at admission, cause of trauma and presence of symptoms related to COVID-19 infection, discharge diagnosis and discharge modes were investigated. RESULTS: The lockdown period led to a reduction of 87.0% in ER admissions with a particular decrease in patients older than 12 years old. Moreover, a trend towards more severe codes and an increase in home-related injuries were observed during the pandemic, whereas the diagnosis of fracture was less frequent in the pre-pandemic group (p < 0.0001). CONCLUSIONS: A significant decrease in the ER attendances was reported during the lockdown. A shift in the cause and type of injury was observed; only the most serious traumas sought medical care with a higher percentage of severe triage codes and fractures.

Incremental diagnostic role of left atrial strain analysis in thrombotic risk assessment of nonvalvular atrial fibrillation patients planned for electrical cardioversion.

During the COVID-19 pandemic, transesophageal echocardiography (TEE) for left atrial appendage thrombosis (LAAT) detection should be limited to situations of absolute necessity. We sought to identify the main conventional and functional echocardiographic parameters associated with LAAT on TEE in non-valvular atrial fibrillation (NVAF) patients planned for electrical cardioversion (ECV). This retrospective study included 125 consecutive NVAF patients (71.5±7.8 yrs, 75 males), who underwent TEE at our Institution between April 2016 and January 2020, to exclude LAAT before scheduled ECV. All patients underwent a transthoracic echocardiography (TTE) implemented with speckle tracking echocardiography (STE) analysis of left atrial (LA) strain and strain rate (SR) parameters. 28% of patients were diagnosed with LAAT, while 72% without LAAT. Compared to controls, patients with LAAT had significantly higher CHA2DS2-Vasc Score and average E/e' ratio, and significantly lower left ventricular ejection fraction (LVEF). Moreover, LA-peak positive global atrial strain (GSA+) and LA-SR parameters were significantly reduced in patients with LAAT. Multivariate logistic regression revealed that, differently from CHA2DS2-Vasc Score, LVEF (OR 0.88, 95%CI 0.81-0.97, p = 0.01), average E/e' ratio (OR 2.36, 95%CI 1.41-3.98, p = 0.001), and LA-GSA+ (OR 0.57, 95%CI 0.36-0-90, p = 0.01) were independently associated with LAAT. LA-GSA+ (optimal cut-off ≤ 9.1%, AUC 0.95) showed the highest diagnostic performance. Finally, a strong linear correlation of LA peak-to-peak SR with both LA appendage filling (r = 0.86) and emptying (r = 0.83) velocities was demonstrated. TTE implemented with STE analysis of LA mechanics improves thrombotic risk assessment of NVAF patients.

Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection.

Growing interest in hypertension-one of the main factors characterizing the cardiometabolic syndrome (CMS)-and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects. New natural compounds, such as peptides, might be useful to treat some hypertensive patients. The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. Peptides isolated from marine vertebrates, invertebrates, seaweeds, or sea microorganisms displayed important biological activities to treat hypertensive patients. Here, we reviewed the anti-hypertensive activities of bioactive molecules isolated/extracted from marine organisms and discussed the associated molecular mechanisms involved. We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.