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.

The prognostic role of interatrial block among COVID-19 patients hospitalized in medicine wards.

INTRODUCTION: Some abnormal electrocardiographic findings were independently associated with increased mortality in patients admitted for COVID-19; however, no studies have focussed on the prognosis impact of the interatrial block (IAB) in this clinical setting. The aim of our study was to assess the prevalence and clinical implications of IAB, both partial and advanced, in hospitalized COVID-19 patients. MATERIALS: We retrospectively evaluated 300 consecutive COVID-19 patients (63.22 ± 15.16 years; 70% males) admitted to eight Italian Hospitals from February 2020 to April 2020 who underwent twelve lead electrocardiographic recording at admission. The study population has been dichotomized into two groups according to the evidence of IAB at admission, both partial and advanced. The differences in terms of ARDS in need of intubation, in-hospital mortality and thromboembolic events (a composite of myocardial infarction, stroke and transient ischaemic attack) have been evaluated. RESULTS: The presence of IAB was noticed in 64 patients (21%). In the adjusted logistic regression model, the partial interatrial block was found to be an independent predictor of ARDS in need of intubation (HR: 1.92; p: .04) and in-hospital mortality (HR: 2.65; p: .02); moreover, the advanced interatrial block was an independent predictor of thrombotic events (HR: 7.14; p < .001). CONCLUSIONS: Among COVID-19 patients hospitalized in medical wards, the presence of interatrial block is more frequent than in the general population and it might be useful as an early predictor for increased risk of incident thrombotic events, ARDS in need of intubation and in-hospital mortality.

Aldosterone and interleukin-6: the synergic effect in COVID-19

Aims Several evidence have identified the role of Interleukin-6 (IL-6) in the cytokine storm induced by COVID-19. Interestingly, the correlation between the serum levels of IL-6 and the plasma aldosterone has already been demonstrated in patients affected by primary aldosteronism (PA). Thus, we suppose that hyperaldosteronism may increase IL-6 levels in COVID-19. Methods and results We report a case of 47-year-old female Covid-19 patient who had developed severe pneumonia complicated by Guillain–Barreé syndrome (GBS). Blood test revealed high levels of IL-6 (serum IL-6: 402 pg/ml) and of its soluble receptor (soluble IL-6 receptor >1900 pg/ml) and she required mechanical ventilation for severe hypoxaemia. Furthermore, the evidence of right adrenal adenoma, resistant hypertension, severe hypokalaemia, and high serum levels of aldosterone with high aldosterone/renin ratio were also consistent with diagnosis of PA. Thus, Spironolactone was administered with rapid improvements in clinical condition. Finally, she was diagnosed with acute motor sensitive neuropathy and started the rehabilitation phase. Conclusions Elevated aldosterone levels in PA may stimulate IL-6 production, inducing more severe forms of COVID-19 with the development of serious complications such as GBS. Hyperaldosteronism may also contribute to the poorest prognosis of patients with secondary aldosteronism such as heart failure and COVID-19, in which elevated IL-6 levels could exert its detrimental effects, mostly on the progression of ventricular dysfunction. Further studies are necessary to evaluate therapy with mineralocorticoid receptors antagonists such as spironolactone in COVID-19.

Personal protective equipment in Covid-19: Evidence-based quality and analysis of YouTube videos after one year of pandemic.

BACKGROUND: The correct use of personal protective equipment (PPE) during the Covid-19 pandemic is mandatory to minimize the contagion risk. The current study aimed to evaluate quality information of YouTube videos on PPE use during the pandemic. METHODS: Using Google Trend tool, the frequency of worldwide YouTube and Google searches for "donning and doffing" was examined. We queried YouTube with terms related to donning and doffing of PPE. Validated quality information assessment tools were used. RESULTS: From the December 1, 2019 to the January 31, 2021, according to YouTube and Google searches, both peaks occurred in April 2020 (69.5% and 72.0%, respectively). Of all videos, 144 were eligible for the analyses. According to misinformation tool, 90 (62.5%) videos contained inaccuracies. The median DISCERN Section 1 ranged from 3 to 5. The median DISCERN Section 3 was 4. According to Global Quality Score, 8.3% (n = 12), 14.6% (n = 21), 22.9% (n = 33), 30.6% (n = 44) and 23.6% (n = 34) were classified as poor, partially poor, moderate, partially good and excellent quality videos, respectively. CONCLUSIONS: Nowadays, YouTube may be recommended as a reliable source of information. Nevertheless, a not negligible number of videos contained inaccuracies. Future authors should improve videos contents to provide more complete information.

The elderly at risk: aldosterone as modulator of the immune response to SARS-CoV-2 infection.

The elderly population is the most susceptible to SARS-CoV-2 infection and develops the worst clinical phenotype with severe pneumonia and cardiac complications. Older COVID-19 patients are also at higher risk of sudden death, mainly attributable to electrolyte disorders and to an uncontrolled inflammatory response. After the identification of ACE 2 as the receptor of SARS-CoV-2 in human cells, several research studies have focused on the role of the activation of Renin Angiotensin System in COVID-19 clinical course. In the present opinion paper, we discuss the role of hyperaldosteronism in the increasing risk of cardiac complications in COVID-19 older patients. In particular, we focus on the immunoregulatory activity of aldosterone, as the last mediator of the Renin Angiotensin System cascade, in activating the innate and adaptive immune response related to SARS-CoV-2 infection in the elderly. Aldosterone may stimulate dendritic cells and the recruitment of monocytes/macrophages in the endothelium of coronary vessels, favoring the production of pro-inflammatory mediators and T-cells response. Higher basal levels of aldosterone together with SARS-CoV-2-induced production may explain the unfavorable course of COVID-19 in the elderly.

Cytokine signature and COVID-19 prediction models in the two waves of pandemics.

In Europe, multiple waves of infections with SARS-CoV-2 (COVID-19) have been observed. Here, we have investigated whether common patterns of cytokines could be detected in individuals with mild and severe forms of COVID-19 in two pandemic waves, and whether machine learning approach could be useful to identify the best predictors. An increasing trend of multiple cytokines was observed in patients with mild or severe/critical symptoms of COVID-19, compared with healthy volunteers. Linear Discriminant Analysis (LDA) clearly recognized the three groups based on cytokine patterns. Classification and Regression Tree (CART) further indicated that IL-6 discriminated controls and COVID-19 patients, whilst IL-8 defined disease severity. During the second wave of pandemics, a less intense cytokine storm was observed, as compared with the first. IL-6 was the most robust predictor of infection and discriminated moderate COVID-19 patients from healthy controls, regardless of epidemic peak curve. Thus, serum cytokine patterns provide biomarkers useful for COVID-19 diagnosis and prognosis. Further definition of individual cytokines may allow to envision novel therapeutic options and pave the way to set up innovative diagnostic tools.

Mechanical complications of myocardial infarction during COVID-19 pandemic: An Italian single-centre experience.

COVID-19 pandemic triggered in many patients the fear to go to the emergency rooms in order to avoid a possible infection. This phenomenon caused a significant reduction in acute coronary syndrome-related interventional procedures with a subsequent increase in critical hospitalizations and post-infarction mechanical complications. A case series of cardiac ruptures during the COVID-19 lockdown and the surgical treatment of a huge post-ischemic cardiac pseudoaneurysm complicated by a "contained" free wall rupture are presented.

Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection.

The ongoing pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has so far infected about 2.42 × 107 (as at 27 August 2020) subjects with more than 820,000 deaths. It is the third zoonotic coronavirus-dependent outbreak in the last twenty years and represents a major infective threat for public health worldwide. A main aspect of the infection, in analogy to other viral infections, is the so-called "cytokine storm", an inappropriate molecular response to virus spread which plays major roles in tissue and organ damage. Immunological therapies, including vaccines and humanized monoclonal antibodies, have been proposed as major strategies for prevention and treatment of the disease. Accordingly, a detailed mechanistic knowledge of the molecular events with which the virus infects cells and induces an immunological response appears necessary. In this review, we will report details of the initial process of SARS-CoV-2 cellular entry with major emphasis on the maturation of the spike protein. Then, a particular focus will be devoted to describe the possible mechanisms by which dendritic cells, a major cellular component of innate and adaptive immune responses, may play a role in the spread of the virus in the human body and in the clinical evolution of the disease.