Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications

Aims: Data on the impact of COVID-19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID-19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline-directed medical therapy (GDMT) and worse outcomes during hospitalization. Methods and results: Data for a total of 3080 consecutive patients with confirmed COVID-19 infection and follow-up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N-terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in-hospital mortality. Conclusions: Patients with COVID-19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID-19 diagnosis. The withdrawal of GDMT was associated with higher mortalit

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Unearthing the soil‐borne microbiome of land plants

17 páginas.- 8 figuras.- referenciasPlant–soil biodiversity interactions are fundamental for the functioning of terrestrial ecosystems. Yet, the existence of a set of globally distributed topsoil microbial and small invertebrate organisms consistently associated with land plants (i.e., their consistent soil-borne microbiome), together with the environmental preferences and functional capabilities of these organisms, remains unknown. We conducted a standardized field survey under 150 species of land plants, including 58 species of bryophytes and 92 of vascular plants, across 124 locations from all continents. We found that, despite the immense biodiversity of soil organisms, the land plants evaluated only shared a small fraction (less than 1%) of all microbial and invertebrate taxa that were present across contrasting climatic and soil conditions and vegetation types. These consistent taxa were dominated by generalist decomposers and phagotrophs and their presence was positively correlated with the abundance of functional genes linked to mineralization. Finally, we showed that crossing environmental thresholds in aridity (aridity index of 0.65, i.e., the transition from mesic to dry ecosystems), soil pH (5.5; i.e., the transition from acidic to strongly acidic soils), and carbon (less than 2%, the lower limit of fertile soils) can result in drastic disruptions in the associations between land plants and soil organisms, with potential implications for the delivery of soil ecosystem processes under ongoing global environmental change.This study work associated with this manuscript was founded by a Large Research Grant from the British Ecological Society (No LRB17\1019; MUSGONET). M.D.-B. was supported from the Spanish Ministry of Science and Innovation for the I + D + i project PID2020-115813RA-I00 funded by MCIN/AEI/10.13039/501100011033 and by the TED2021-130908B-C41 funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/PRTR.” R.O.-H. was supported by the Ramón y Cajal program from the MICINN (RYC-2017 22032), by the Spanish Ministry of Science and Innovation for the I + D + i project PID2019-106004RA-I00 funded by MCIN/AEI/10.13039/501100011033, by the Fondo Europeo de Desarrollo Regional (FEDER) y la Consejería de Transformación Económica, Industria, Conocimiento y Universidades of the Junta de Andalucía (FEDER Andalucía 2014-2020 Objetivo temático “01 - Refuerzo de la investigación, el desarrollo tecnológico y la innovación”): P20_00323 (FUTUREVINES), and by the Fondo Europeo Agrícola de Desarrollo Rural (FEADER) through the “Ayudas a Grupos operativos de la Asociación Europea de Innovación (AEI) en materia de productividad y sostenibilidad agrícolas”, References: GOPC-CA-20-0001 (O.G. Suelos Vivos) and GO2022-01 (O.G. Viñas Vivas). TG and TUN were supported by the research project J4-1766 “Methodology approaches in genome-based diversity and ecological plasticity study of truffles from their natural distribution areas”, the Research Program in Forest Biology, Ecology and Technology (P4-0107), and a Young Researcher scheme (TUN) of the Slovenian Research Agency. J.L.B.-P. is supported by the EMERGIA programme of the Junta de Andalucía (EMC21_00207).Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Large perpendicular magnetic anisotropy in nanometer-thick epitaxial graphene/co/heavy metal heterostructures for spin-orbitronics devices

Nanometer-thick epitaxial Co films intercalated between graphene (Gr) and a heavy metal (HM) substrate are promising systems for the development of spin-orbitronic devices due to their large perpendicular magnetic anisotropy (PMA). A combination of theoretical modeling and experiments reveals the origin of the PMA and explains its behavior as a function of the Co thickness. High quality epitaxial Gr/Co-n/HM(111) (HM = Pt,Ir) heterostructures are grown by intercalation below graphene, which acts as a surfactant that kinetically stabilizes the pseudomorphic growth of highly perfect Co face-centered tetragonal (fct) films, with a reduced number of stacking faults as the only structural defect observable by high-resolution scanning transmission electron microscopy (STEM). Magneto-optic Kerr effect (MOKE) measurements show that such heterostructures present PMA up to large Co critical thicknesses of about 4 nm (20 ML) and 2 nm (10 ML) for Pt and Ir substrates, respectively. X-ray magnetic circular dichroism (XMCD) measurements show an inverse power law of the anisotropy of the orbital moment with Co thickness, reflecting its interfacial nature, that changes sign at about the same critical values. First principles calculations show that, regardless of the presence of graphene, ideal Co fct films on HM buffers do not sustain PMAs beyond around 6 mLs due to the in-plane contribution of the inner bulk-like Co layers. The large experimental critical thicknesses sustaining PMA can only be retrieved by the inclusion of structural defects that promote a local hcp stacking such as twin boundaries or stacking faults. Remarkably, a layer resolved analysis of the orbital momentum anisotropy reproduces its interfacial nature, and reveals that the Gr/Co interface contribution is comparable to that of the Co/Pt(Ir).Financial support from MINECO (Grant Nos. RTI2018-097895-B-C41, RTI2018-097895-BC42 and RTI2018-097895-B-C43 (FUN-SOC), PID2019- 103910GB-I00, FIS2016-78591-C3-1-R and FIS2016-78591- C3-2-R (SKYTRON), PGC2018-098613-B-C21 (SpOrQuMat), PCI2019-111908-2 and PCI2019-111867-2 (FLAGERA 3 grant SOgraphMEM)], from Regional Government of Madrid (grant number P2018/NMT-4321 (NANOMAGCOST-CM)) and from Gobierno Vasco-UPV/EHU (grant numbers GIU18/138 and IT-1246-19). We acknowledge experiments at ALBA BL29 via proposal no. 2019023333. IMDEA-Nanociencia acknowledges support from the “Severo Ochoa” Program for Centres of Excellence in R&D (MINECO, Grant SEV-2016-0686

Differential reporting of biodiversity in two citizen science platforms during COVID-19 lockdown in Colombia

The COVID-19 pandemic highlighted the potential of using data from long-term citizen science projects to answer questions about the impacts of unexpected events on biodiversity. We evaluate the suitability of data from the citizen science platforms iNaturalist and eBird to describe the effects of the "anthropause" on biodiversity observation in Colombia. We compared record distribution according to human footprint, sampling behaviors, overall and conservation priority species composition during the strictest phase of the COVID-19 lockdown in 2020 to the same periods in 2015-2019. Overall participation in both platforms during the lockdown was high when compared to previous years, but records were concentrated on highly-transformed regions, had lower sampling efforts, and fewer species were recorded. For eBird, species composition was similar to that observed in previous years, and records of species of conservation concern declined in proportion to the decrease in overall species richness across samples. For iNaturalist, the species pool sampled each year remained too dissimilar for comparisons. Once differences in observer behaviors are accounted for, data from these platforms can be used in unplanned comparisons of relatively common species, in regions with high levels of human transformation, and at narrowly defined geographical contexts. To increase the potential of citizen science to monitor rarer species, more natural areas, or be used in large-scale analyses, we need to build and strengthen more diverse networks of observers that can further promote decentralization, democratization, and cost-effectiveness in biodiversity research

Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism.

Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available