Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

Targeted genetic analysis unveils novel associations between ACE I/D and APO T158C polymorphisms with D-dimer levels in severe COVID-19 patients with pulmonary embolism.

Only a percentage of COVID-19 patients develop thrombotic complications. We hypothesized that genetic profiles may explain part of the inter-individual differences. Our goal was to evaluate the genotypic distribution of targeted DNA polymorphisms in COVID-19 patients complicated (PE+) or not (PE-) by pulmonary embolism. We designed a retrospective observational study enrolling N = 94 consecutive patients suffering severe COVID-19 with pulmonary embolism (PE+, N = 47) or not (PE-, N = 47) during hospitalization. A panel of N = 13 prothrombotic DNA polymorphisms (FV R506Q and H1299R, FII G20210A, MTHFR C677T and A1298C, CBS 844ins68, PAI-1 4G/5G, GPIIIa HPA-1 a/b, ACE I/D, AGT T9543C, ATR-1 A1166C, FGB - 455G > A, FXIII103G > T) and N = 2 lipid metabolism-related DNA polymorphisms (APOE T 112C and T158C) were investigated using Reverse Dot Blot technique. Then, we investigated possible associations between genotypic subclasses and demographic, clinical, and laboratory parameters including age, obesity, smoking, pro-inflammatory cytokines, drug therapy, and biomarkers of thrombotic risk such as D-dimer (DD). We found that 58.7% of PE+ had homozygous mutant D/D genotype at ACE I/D locus vs. PE- (40.4%) and 87% of PE+ had homozygous mutant C/C genotype at APOE T158C locus vs. PE- (68.1%). In PE+ group, DD levels were significantly higher in D/D and I/D genotypes at ACE I/D locus (P = 0.00066 and P = 0.00023, respectively) and in C/C and T/C genotypes at APOE T158C locus (P = 1.6e-06 and P = 0.0012, respectively) than PE- group. For the first time, we showed significant associations between higher DD levels and ACE I/D and APOE T158C polymorphisms in PE+ vs. PE- patients suggesting potential useful biomarkers of poor clinical outcome.

Respiratory Intensive Care Unit management and efficacy during the COVID-19 outbreak in Naples, Italy.

The World Health Organization declared the Coronavirus Diseases 2019 (COVID-19) outbreak a global pandemic on March 11, 2020. COVID-19 had an impact on over 500 million people worldwide. According to the American Thoracic Society criteria, the respiratory spectrum of this disease ranges from mild illness to severe pneumonia, with the latter occurring in a not insignificant 15% of patients. A rapid increase in the incidence of COVID-19 pneumonia cases has been observed all over the world, resulting in a saturation of the Intensive Care Unit's capacity (ICUs). Because of this impressive outbreak, the ICU beds and invasive mechanical ventilators reached their capacity. Non-invasive supportive care has become an important option for keeping respiratory conditions under control. As a result, proper healthcare resource management was required to ensure adequate patient care. Respiratory Intensive Care Units (RICUs) have become a useful resource for managing complex patients due to a shortage of ICU capacity. This highlighted the importance of RICUs, where patients with moderate to severe respiratory failure can be treated with non-invasive respiratory support rather than being admitted to the ICU. The clinical outcomes and baseline characteristics of patients admitted to the RICU of Cotugno Hospital, a tertiary referral center in Naples (Italy), from January 2021 to October 2021 are described in this report.

The Serum Metabolome of Moderate and Severe COVID-19 Patients Reflects Possible Liver Alterations Involving Carbon and Nitrogen Metabolism.

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.

Bleeding events in COVID-19: the other side of the coin?

We present three cases of patients affected by severe SARS-CoV-2-related pneumonia treated with a low molecular weight heparin for prevention or treatment of pulmonary embolism, who presented a major bleed, in particular an ileopsoas haematoma that caused severe anaemia; in one case it was fatal. In the recent outbreak of novel coronavirus infection, significantly abnormal coagulation parameters in SARS-CoV-2 infection occur very often, but complications in the opposite direction such as bleeding diathesis are very rare. In these cases, there are different levels of gravity: for one patient the major bleed required the anticoagulant therapy to be stopped until bleeding stabilized, one patient needed interventional radiology and one patient died.

A Rare Evolution to Pneumopericardium in Patient with COVID-19 Pneumonia Treated with High Flow Nasal Cannula.

Infection with severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) which was revealed an official pandemic by the World Health Organization on 11 March 2020. The current pandemic, the third of this decade, is the worst in terms of suffering and deaths related. COVID-19 represents an unprecedented challenge for medical communities and patients around the world. High-resolution computed tomography of the chest (HRCT) is a fundamental tool in both management and diagnosis of the disease. Imaging plays an essential role in the diagnosis of all the manifestations of the disease and its complications and the correct use and interpretation of imaging tests are essential. Pneumomediastinum has been reported rarely in COVID-19 patients. We were one of the first groups to share our experiences in uncommon parenchymal complications of COVID-19 with spontaneous pneumothorax and pneumomediastinum, but also with new-onset bronchiectasis and cysts. A finding of pneumopericardium is also unusual. We hereby report a rare case of spontaneous pneumopericardium in a patient with COVID-19 pneumonia treated only with a high-flow nasal cannula (HFNC).

The Angiotensin Converting Enzyme Deletion/Deletion Genotype Is a Risk Factor for Severe COVID-19: Implication and Utility for Patients Admitted to Emergency Department.

Background and objective: Insertion/deletion polymorphisms of angiotensin-converting enzyme (ACE) have been previously described in association with adult respiratory distress syndrome (ARDS) and correlated to outcome. The ACE deletion/deletion(D/D)genotype represents a marker of thrombosis in subjects apparently without predisposing factors and/or traditional thrombophilic alterations and increases the risk of venous thromboembolism in subjects in whom a thrombogenic condition occurs. Thrombosis seems to play a role very early in the disease caused by SARS-CoV-2, in particular in those with severe COVID-19 pneumonia. The counterbalance between angiotensin-converting enzyme (ACE) and ACE2 activities in COVID-19 disease may play a crucial role in the thrombo-inflammatory process. We hypothesised that a genetic predisposition could condition the severity and complications of SARS-CoV-2 infection. Materials and methods: We conducted a spontaneous, single centre observational study in the Sub-Intensive Care Unit of A.O.R.N. Ospedali dei Colli, Cotugno Hospital, Naples (Italy). In this study, we performed genetic screening for ACE D/D genotype and other thrombophilic mutations in 20 patients affected by ARDS related to COVID-19 pneumonia, compared to 19 age- and sex-matched healthy controls. Results: All tested patients had multiple polymorphisms and, in particular, a significantly higher prevalence of ACE D/D polymorphism in severe COVID-19 patients Conclusion: We found that the majority of patients who tested positive for ACE D-D genotype and who were not associated with other risk factors for VTE showed an evolution to ARDS. This finding could have a predicting role in the selection of patients more prone to developing severe COVID-19 during clinical observation in emergency department.

Pathophysiology of Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT) and Vaccine-Induced Thrombocytopenic Thrombosis (VITT) and Their Diagnostic Approach in Emergency.

SARS-CoV-2 induced a pandemic that is reported to have started in Asia and was then extended to other countries in the world. Main clinical aspects of this viral infection have been lung injuries with severe pneumonia requiring prolonged hospitalization and associated morbidities such as venous thromboembolism and/or superinfection by bacteria, fungus or other pests. Immediately there was a need to develop a sustainable therapeutic strategy, such as vaccination. Vaccines against Covid-19, in fact, exert a protective action for common people and reduce viral diffusion. Yet, vaccination of a large number of people raises the question of a well-known complication of several types of vaccines; this complication is immune thrombocytopenia, which is sometimes associated with thrombosis as well. In this short review, we summarized mechanisms involved in the pathogenesis of vaccine-induced prothrombotic immune thrombocytopenia and vaccine-induced thrombocytopenic thrombosis.

Exercise and Chronic Obstructive Pulmonary Disease (COPD).

Systemic effects of COPD lead to cardiovascular co-morbidities, muscle wasting and osteoporosis that, in turn, lead to inactivity and physical deconditioning. This evolution has a direct influence on the health-related quality of life (HRQoL) of patients suffering from this respiratory disease. Pharmacological therapy leads to improvement in shortness of breath, but it has a limited effect on the physical deconditioning. Pulmonary rehabilitation relieves dyspnoea and fatigue, improves emotional function and enhances the sense of control that individuals have over their condition. These improvements are moderately substantial and clinically significant. Rehabilitation serves as an essential component of the management of COPD and is beneficial in improving health-related quality of life and exercise capacity.

Different presentation of pulmonary parenchymal disruption in COVID-19 pneumonia. Case series of Sub-Intensive Care Unit in Naples, Italy.

The coronavirus disease 2019 (COVID-19) is a recent pandemic that affected more than 5 million people worldwide. Chest high resolution computed tomography (HRCT) is an essential tool in diagnosis and management of the disease. Pulmonary parenchymal opacity is a typical sign of the disease, but not the only one. Pneumothorax, pneumomediastinum, bronchiectasis and cysts are probably underrated complications of COVID-19 that can worsen prognosis, in terms of prolonged hospitalization and need of oxygen therapy. In our single center case series, we outline four different manifestations of pneumothorax, pneumomediastinum and cysts in hospitalized patients with COVID-19 pneumonia.

Acute and Chronic Effects of Noninvasive Ventilation on Left and Right Myocardial Function in Patients with Obstructive Sleep Apnea Syndrome: A Speckle Tracking Echocardiographic Study.

BACKGROUND: In patients with obstructive sleep apnea syndrome (OSAS), repetitive hypoxia due to sleep-induced apnea adversely affects the interaction between myocardial oxygen demand and supply, resulting in the development of subclinical cardiac dysfunction. The purpose of the study was to analyze the different involvement of left and right heart myocardial function in patients with OSAS treated with noninvasive ventilation (NIV). METHODS: Conventional Doppler echocardiography, Doppler myocardial imaging (DMI), and two-dimensional speckle tracking echocardiography (2DSTE) of left (LV) and right ventricular (RV) longitudinal and right atrial (RA) deformation were performed in 55 patients with OSAS undergoing NIV (M/F 38/17; mean age 67.8 ± 11.2 years). LV and RV global longitudinal strain (GLS) was calculated by averaging local strain along the entire right and left ventricle, before and during NIV, and after 6 months of nocturnal NIV therapy. RESULTS: LV morphology was comparable before and during NIV, whereas LV ejection fraction and LV DMI early diastolic peak velocity were significantly improved in patients with OSAS during NIV, as was LV regional peak myocardial strain (P < 0.001). RV diameters were slightly increased in patients with OSAS during ventilation, whereas pulmonary artery systolic pressure (PASP), RV GLS, and regional peak myocardial RV strain were significantly reduced during ventilation (P < 0.0001). RA transverse diameters and RA area were also slightly increased during NIV, whereas RA lateral wall strain was reduced (P < 0.001). Acute RV myocardial impairment completely reversed at follow-up, with a decrease in PASP and subsequent increase in both RV and RA myocardial performance. CONCLUSIONS: Conventional 2DSTE is a useful tool for assessing left and right heart morphology and myocardial deformation in patients with OSAS and for monitoring both acute and chronic effects of NIV.

miR-338-3p is over-expressed in blood, CFS, serum and spinal cord from sporadic amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Ninety percent of ALS patients are sporadic cases (sALS) with no clear genetic linkage. Accumulating evidence indicates that various microRNAs (miRNAs), expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, microRNA dysregulation contributes to some mental disorders and neurodegeneration diseases. In our research, the expression of one selected miRNA, miR-338-3p, which previously we have found over-expressed in blood leukocytes, was studied in several different tissues from sALS patients. For the first time, we detected a specific microRNA disease-related upregulation, miR-338-3p, in blood leukocytes as well in cerebrospinal fluid, serum, and spinal cord from sALS patients. Besides, staining of in situ hybridization showed that the signals of miR-338-3p were localized in the grey matter of spinal cord tissues from sALS autopsied patients. We propose that miRNA profiles found in tissue samples from sALS patients can be relevant to understand sALS pathogenesis and lead to set up effective biomarkers for sALS early diagnosis.

Telomerase expression in amyotrophic lateral sclerosis (ALS) patients.

Telomerase and telomeric complex have been linked to a variety of disease states related to neurological dysfunction. In amyotrophic lateral sclerosis (ALS) patients, telomerase activity, as human telomerase reverse transcriptase (hTERT) expression, has not been characterized yet. Here, for the first time, we characterized telomerase and related pathway in blood sample and spinal cord from ALS patients compared with healthy controls. We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS. As a consequence of the reduced telomerase activity, we identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy control group.

Sleep breathing disorders and nocturnal respiratory pattern in patients with glycogenosis type II.

Patients affected by glycogenosis type II frequently present sleep disordered breathing. The presence of symptoms suggestive of sleep breathing disorders was investigated, by a questionnaire, in 10 patients, affected by adult or juvenile forms of glycogenosis type II. Diurnal respiratory function, diaphragm weakness and nocturnal respiratory pattern were evaluated at the enrolment. In patients presenting sleep disordered breathing, the same parameters were re-evaluated after treatment with assisted non invasive ventilation. Out of 10 patients, 5 presented symptoms suggestive of sleep-disordered breathing at the baseline, 2 a pattern of sleep apnea syndrome and 3 nocturnal hypoventilation. All patients presented diaphragmatic weakness. No correlation was found between forced vital capacity values (FVC) in sit position and nocturnal respiratory disorders. Five patients with respiratory disorders were treated with non invasive ventilation. All patients - after one month of treatment - showed an improvement in symptoms with reduced diurnal hypersomnia (ESS < 10), absence of morning headaches and nocturnal awakenings, and reduced nicturia regardless the modality of ventilation. We recommend that all patients with glycogenosis type II, once diagnosed, are carefully monitored for the development of respiratory involvement, even in the absence of reduced FVC values and in the early stages of the disease, to receive appropriate therapy.

Indications and techniques of non-invasive ventilation (NIV) in neuromuscular diseases.

The neuromuscular patients may experience the need for respiratory support due to the onset of respiratory failure. Some skills are essential to achieve therapeutic success. In addition to technical knowledge, it is essential to have knowledge relating to individual neuromuscular diseases. The availability of alternative respiratory supports and various interfaces can be a valuable weapon at different moments in the course of the neuromuscular disease. Furthermore, the doctor-patient relationship plays a key role as does taking care of the patient's psychological sphere.

Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p = 0.04 and p = 0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p = 0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p = 0.0004, p < 0.0001, p = 0.007, respectively) and, at the one-year follow-up, they displayed a significantly higher FEV1 and DLCO decline (p = 0.0022, p = 0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p = 0.0083, p = 0.043, p = 0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.

An unusual way to improve lung function in congenital myopathies: the power of singing.

Congenital myopathies (CMs) are a clinically and genetically heterogeneous group of disorders characterized by early onset weakness, hypotonia and characteristic structural abnormalities in muscle fibres. Hypotonia and weakness can be present at birth or appear in infancy, and a static or slowly progressive clinical course may present with muscle weakness, loss of spontaneous movement, involuntary muscle activity, and muscle atrophy. Often patients develop a restrictive syndrome and respiratory failure and require respiratory support In our case, we described lung improvement and respiratory muscle training due to singing in a young patient, affected by CMs with a poor adherence to non-invasive mechanical ventilation.

Psychological Factors Influencing Adherence to NIV in Neuromuscular Patients Dependent on Non Invasive Mechanical Ventilation: Preliminary Results.

BACKGROUND: Non-invasive ventilation (NIV) is associated with improvement of both morbility and mortality in patients affected by neuromuscular diseases with chronic respiratory failure. Several studies have also shown that long-term NIV positively impacts the patient's quality of life and perception of disease status. Its effectiveness is likely related to the adherence to NIV. Several factors, patient- and not patient-related, may compromise adherence to NIV, such as physical, behavioral, familiar, and social issues. Few data are currently available on the role of psychological factors in influencing NIV adherence. MATERIALS AND METHODS: In this pilot study, we evaluated the adherence to NIV in a group of 15 adult patients with neuromuscular diseases (Duchenne muscular dystrophy, myotonic dystrophy, and amyotrophic lateral sclerosis) in relation to their grade of depression assessed by the Beck Depression Inventory (BDI) questionnaire. Other data were collected, such as clinical features (age and sex), use of anxiolytic drugs, the presence of a family or professional caregiver, the quality of patient-physician relationship, the beginning of psychological support after BDI screening, and the family acceptance of NIV. NIV adherence was definied as the use of NIV for at least 4 h per night on 70% of nights in a month. RESULTS: The overall rate of NIV adherence was 60%. Based on the BDI questionnaire, patients who were non-adherent to NIV had a higher rate of depression, mainly observed in the oldest patients. The acceptance of NIV by the family and positive physician-patient interaction seem to favor NIV adherence. CONCLUSION: Depression can interfere with NIV adherence in patients with neuromuscolar diseases.