The COVID confinement measures and EU labour markets

This paper assesses the potential impact of the early 2020 COVID confinement measures on EU labour markets, on the basis of an analysis of the restrictions on economic activity imposed in three EU Member States (Italy, Spain and Germany). Following the legislative measures adopted, we classify all economic sectors into different categories according to the likely impact of the COVID crisis, and compare the share of employment that is likely to be strongly affected in each country. Once this is done, we apply these categories of sectors to recent data on EU employment and estimate the groups of workers that would be more or less affected by the economic lockdown measures. Finally, we use all this information to speculate about possible mid-term developments and broader socio-economic implications of the COVID crisis in Europe.JRC.B.4-Human Capital and Employmen

Impact of operator experience and wiring technique on procedural efficacy of trans-radial percutaneous chronic total occlusion recanalization performed by dedicated radialists

The efficacy of trans-radial approach (TRA) in chronic total occlusions (CTO) percutaneous coronary interventions (PCI) is not well established. Thus, we sought to review the feasibility and long-term results of TRA for CTO PCI performed by dedicated TRA operatorsof our center

Advanced age, time to treatment and long-term mortality: single centre data from the FAST-STEMI network

Background. Optimization of the techniques and larger accessibility to mechanical reperfusion have significantly improved the outcomes of patients with ST-segment elevation myocardial infarction (STEMI). However, suboptimal results have been observed in certain higher-risk subsets of patients, as in advanced age, where the benefits of primary PCI are more debated. We evaluated the impact of systematic primary percutaneous coronary intervention (PCI) and an optimized STEMI network on the long-term prognosis from a single centre experience.Methods. We included STEMI patients included in the FAST-STEMI network between 2016 and 2019. Ischemia duration was defined as the time from symptoms onset to coronary reopening (pain-to-balloon, PTB). The primary study endpoint (PE) was a composite of mortality and recurrent MI at long-term follow-up. Indywidual outcome endpoints were also assessed.Results. We included 253 patients undergoing primary PCI and discharged alive. Mean age was 67.2 ± 12.5 years, 75.1% males and 19.8% diabetics. At a median follow-up of 581 [307–922] days, the primary endpoint occurred in 24 patients (7.9%), of whom 5.5% died. The occurrence of a cardiovascular event was significantly associated with advanced age (p < 0.001), renal failure (p = 0.03), lower ejection fraction at discharge (p = 0.04) and longer in-hospital stay (p = 0.01). The median PTB was 198 minutes [IQR: 125–340 min], that was significantly longer among patients experiencing the PE (p = 0.01). A linear relationship was observed between age and PTB (r = 0.13, p = 0.009). However, both age ≥ 75 years and PTB above the median emerged as independent predictors of the primary endpoint (age: HR [95%CI] = 5.56 [2.26–13.7], p < 0.001, PTB: HR [95%CI] = 3.59 [1.39–9.3], p = 0.01). Similar results were observed for overall mortality.Conclusion. The present study shows that among STEMI patients undergoing primary PCI in a single centre, the duration of ischemia and advance age are independently associated to long-term mortality and recurrent myocardial infarction. However, longer time to reperfusion was observed among elderly patients

Impact of operator experience and wiring technique on procedural efficacy of trans-radial percutaneous chronic total occlusion recanalization performed by dedicated radialists

Background: The efficacy of trans-radial approach (TRA) in chronic total occlusions (CTO) percutaneous coronary interventions (PCI) is not well established. Thus, we sought to review the feasibility and long-term results of TRA for CTO PCI performed by dedicated TRA operatorsof our center. Methods: CTO PCI performed by dedicated radialists were considered. Primary end-points were "PCI success" (stent implantation with residual stenosis < 20% and TIMI 3) and "patient success" (PCI success in a first or second attempt). Vascular complications and major adverse cardiac events (MACE) were also assessed. Procedures were divided into: Period 1 — no systematic adoption of TRA nor systematic wire selection, and Period 2 — systematic TRA with stepwise wire selection. The starting guidewire was initially an intermediate wire (Period 2a), and, thereafter, a tapered soft polymeric guidewire (Period 2b). Results: Two operators performed 167 TRA PCI on CTO in 158 patients. PCI success rate was 74.3% and patient success rate was 78.5%. Drug-eluting stents were implanted in 95.1% of successful procedures. One (0.6%) patient had a (minor) vascular complication. After a mean follow-up of 580 days, 93.7% of patients were free from MACE. PCI success (57.1% in Period 1 vs. 76.5% in Period 2a vs. 80.5% in Period 2b, p = 0.029) and patient success (62.5% in Period 1 vs. 77.8% in Period 2a vs. 86.1% in Period 2b, p = 0.025) significantly improved during the study. Conclusions: CTO PCI by TRA is safe and feasible. Its efficacy seems to be strongly dependenton operator experience with CTO techniques and may be influenced by the strategy of guidewire selection

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

Impact of operator experience and wiring technique on procedural efficacy of trans-radial percutaneous chronic total occlusion recanalization performed by dedicated radialists

Background: The efficacy of trans-radial approach (TRA) in chronic total occlusions (CTO) percutaneous coronary interventions (PCI) is not well established. Thus, we sought to review the feasibility and long-term results of TRA for CTO PCI performed by dedicated TRA operatorsof our center.Methods: CTO PCI performed by dedicated radialists were considered. Primary end-points were “PCI success” (stent implantation with residual stenosis &lt; 20% and TIMI 3) and “patient success” (PCI success in a first or second attempt). Vascular complications and major adverse cardiac events (MACE) were also assessed. Procedures were divided into: Period 1 — no systematic adoption of TRA nor systematic wire selection, and Period 2 — systematic TRA with stepwise wire selection. The starting guidewire was initially an intermediate wire (Period 2a), and, thereafter, a tapered soft polymeric guidewire (Period 2b).Results: Two operators performed 167 TRA PCI on CTO in 158 patients. PCI success rate was 74.3% and patient success rate was 78.5%. Drug-eluting stents were implanted in 95.1% of successful procedures. One (0.6%) patient had a (minor) vascular complication. After a mean follow-up of 580 days, 93.7% of patients were free from MACE. PCI success (57.1% in Period 1 vs. 76.5% in Period 2a vs. 80.5% in Period 2b, p = 0.029) and patient success (62.5% in Period 1 vs. 77.8% in Period 2a vs. 86.1% in Period 2b, p = 0.025) significantly improved during the study.Conclusions: CTO PCI by TRA is safe and feasible. Its efficacy seems to be strongly dependenton operator experience with CTO techniques and may be influenced by the strategy of guidewire selection

Angiographic assessment of microvascular perfusion-Myocardial blush in clinical practice

Assessment of myocardial “blush” by either Myocardial Blush Grade or TIMI Myocardial Perfusion Grade, is the angiographic method currently preferred to confirm myocardial tissue-level perfusion after primary percutaneous intervention. This review focuses on the utility of angiographic “blush” as a simple, widely available, and virtually costless technique for the immediate diagnosis of microvascular impairment at the time of acute catheterization. We comprehensively outline the available evidence behind the “blush,” its use in clinical practice, and draw comparisons with other new technologies for assessment of microvascular integrity