Differential host responses within the upper respiratory tract and peripheral blood of children and adults with SARS-CoV-2 infection (preprint)

Age is among the strongest risk factors for severe outcomes from SARS-CoV-2 infection. We sought to evaluate associations between age and both mucosal and systemic host responses to SARS-CoV-2 infection. We profiled the upper respiratory tract (URT) and peripheral blood transcriptomes of 201 participants (age range of 1 week to 83 years), including 137 non-hospitalized individuals with mild SARS-CoV-2 infection and 64 uninfected individuals. Among uninfected children and adolescents, young age was associated with upregulation of innate and adaptive immune pathways within the URT, suggesting that young children are primed to mount robust mucosal immune responses to exogeneous respiratory pathogens. SARS-CoV-2 infection was associated with broad induction of innate and adaptive immune responses within the URT of children and adolescents. Peripheral blood responses among SARS-CoV-2-infected children and adolescents were dominated by interferon pathways, while upregulation of myeloid activation, inflammatory, and coagulation pathways was observed only in adults. Systemic symptoms among SARS-CoV-2-infected subjects were associated with blunted innate and adaptive immune responses in the URT and upregulation of many of these same pathways within peripheral blood. Finally, within individuals, robust URT immune responses were correlated with decreased peripheral immune activation, suggesting that effective immune responses in the URT may promote local viral control and limit systemic immune activation and symptoms. These findings demonstrate that there are differences in immune responses to SARS-CoV-2 across the lifespan, including between young children and adolescents, and suggest that these varied host responses contribute to observed differences in the clinical presentation of SARS-CoV-2 infection by age.

The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions (preprint)

Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings.

Porous Cellulose Thin Films as Sustainable and Effective Antimicrobial Surface Coatings.

In the present work, we developed an effective antimicrobial surface film based on sustainable microfibrillated cellulose. The resulting porous cellulose thin film is barely noticeable to human eyes due to its submicrometer thickness, of which the surface coverage, porosity, and microstructure can be modulated by the formulations and the coating process. Using goniometers and a quartz crystal microbalance, we observed a threefold reduction in water contact angles and accelerated water evaporation kinetics on the cellulose film (more than 50% faster than that on a flat glass surface). The porous cellulose film exhibits a rapid inactivation effect against SARS-CoV-2 in 5 min, following deposition of virus-loaded droplets, and an exceptional ability to reduce contact transfer of liquid, e.g., respiratory droplets, to surfaces such as an artificial skin by 90% less than that from a planar glass substrate. It also shows excellent antimicrobial performance in inhibiting the growth of both Gram-negative and Gram-positive bacteria (Escherichia coli and Staphylococcus epidermidis) due to the intrinsic porosity and hydrophilicity. Additionally, the cellulose film shows nearly 100% resistance to scraping in dry conditions due to its strong affinity to the supporting substrate but with good removability once wetted with water, suggesting its practical suitability for daily use. Importantly, the coating can be formed on solid substrates readily by spraying, which requires solely a simple formulation of a plant-based cellulose material with no chemical additives, rendering it a scalable, affordable, and green solution as antimicrobial surface coating. Implementing such cellulose films could thus play a significant role in controlling future pan- and epidemics, particularly during the initial phase when suitable medical intervention needs to be developed and deployed.

TU-159. Repetitive transcranial magnetic stimulation as a therapeutic approach in a case of NORSE

Introduction: Status epilepticus (SE) is a neurologic emergency with high-mortality rates that requires early diagnosis and prompt treatment to improve the patient's chances. A SE is called refractory (RSE) when seizures are uncontrollable despite intravenous (IV) benzodiazepine in addition to anti-epileptic drugs (AED). If seizures continue despite IV-AED and/or IV-anesthetics, that is designated as super-RSE (SRSE). Recently, new-onset RSE (NORSE) has been described. The current armamentarium of AEDs, immunomodulation-drugs and non-pharmacological therapies available, including neuromodulation techniques, has been used to treat RSE. Lately, the use, efficacy, and safety of repetitive-transcranial-magnetic-stimulation (rTMS) are well known. Method(s): In October 2020, a 23-year-old male with a low level of consciousness and clinical SE was admitted to an intensive care unit. A febrile peak, the previous week, was the only pertinent data. SARS-CoV2 test was negative, although it became positive a week later. While in the hospital, SE therapeutic protocol was followed (antivirals, antibiotics, and AEDs, anesthetics, including cortical electrical silence pentothal-induced, immunomodulation drugs (tocilizumab, anakinra), and ketogenic diet) without achieving seizure control. Despite the lack of continuous electroencephalography (EEG) monitorization, daily EEGs were recorded and a diffuse slow-wave cortical activity led the way to bihemispheric fronto-temporal (FT) seizures;left-FT SE was also registered. On the 49th day, the decision was made to administer rTMS. Previously, the epileptiform zone had been located in the right-FT region. He received ten sessions of low-frequency (1-Hz) rTMS in a middle point between C4/T4. No side effects were reported. Result(s): After the first sessions, the patient's level of consciousness improved, and the EEG showed progressive improvement of the cortical slowing and the epileptiform activity over the following days. By the time of discharge, EEG activity was almost normal with some epileptiform discharge still present on the EEG record. Conclusion(s): To our knowledge, a few case series have been published on the use of low-frequency rTMS as a therapeutic approach in SE. Low-frequency rTMS applied over the active epileptogenic focus may swap the cortical excitability toward an inhibitory direction by inducing synaptic plasticity through a long-term depression mechanism, which translates into SE suppression. We cannot confirm that rTMS was the only reason for the positive outcome in this particular patient. However, the outstanding improvement of the EEG activity since the administration of rTMS, accompanied by the progressive recovery of the level of consciousness, means that this technique should be taken into account as a potential therapeutic option in the early onset of SE given its efficacy, and its harmless characteristics. Copyright © 2022

Assessing the implementation of a multi-component hypertension program in a Guatemalan under-resourced dynamic context: An application of the RE-AIM/PRISM extension for sustainability and health equity (preprint)

Background: The COVID-19 pandemic necessitated rapid changes in the delivery of care across public primary care settings in rural Guatemala in 2020. In response, a hypertension program implemented within the public primary care system required multiple adaptations, providing an illustrative example of dynamic implementation amidst changing context in an under-resourced setting. This study describes the evolvability of an evidence-based intervention (EBI; protocol-based hypertension treatment) and one of its main implementation strategies (team-based collaborative care) during the COVID-19 pandemic and discusses implications for health equity and sustainability. Methods: This convergent mixed methods analysis assessed implementation across five Ministry of Health districts during the initial phase of the pandemic. Qualitative and quantitative data were collected, analyzed, and integrated, informed by the RE-AIM (Reach, Effectiveness, Adoption, Implementation Maintenance) Framework’s extension for sustainability, and its contextual enhancement, PRISM (Pragmatic, Robust, Implementation and Sustainability Model). For RE-AIM, we focused on the “Implementation” domain, operationalizing it qualitatively as continued delivery and adaptations to the EBI and implementation strategy, and quantitatively as the extent of delivery over time. We conducted 18 in-depth interviews with health providers / administrators (n=8) and study staff (n=10) and performed a matrix-based thematic-analysis. Qualitative results informed the selection of quantitative implementation summarized as behavior over time graphs. Quantitative implementation data and illustrative quotes are presented as joint displays. Results: In relation to implementation, several organic adaptations hindered delivery, threatened sustainability, and may have exacerbated health inequities. Planned adaptations enhanced program delivery and may have supported improved equity and sustainability. Salient PRISM factors that influenced implementation included “Organizational perspective of the EBI”, “Fit” and “Implementation and sustainability infrastructure”. Facilitators to continued delivery included the perception that the EBI is beneficial, program champions, and healthcare team organization. Barriers included the perception that the EBI is complicated, competition with other primary care activities, and temporary suspension of services due to COVID-19. Conclusions: Multi-level contextual changes led to numerous adaptations of the EBI and implementation strategy. Systems thinking approaches may shed light on how a program’s sustainability and its equitable delivery are influenced by adaptations over time in response to dynamic, multi-level contextual factors. Trial registration: NCT03504124

COVID-19 progression and convalescence in common variable immunodeficiency patients shows incomplete adaptive responses and persistent inflammasome activation (preprint)

Patients with common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, are characterized by hypogammaglobulinemia, poorly protective vaccine titers and increased susceptibility to infections. New pathogens such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), might constitute a particular threat to these immunocompromised patients since many of them experience a slower recovery and do not achieve full response to SARS-CoV-2 vaccines. To define the molecular basis of the altered immune responses caused by SARS-CoV-2 infection in CVID patients, we generated longitudinal single-cell datasets of peripheral blood immune cells along viral infection and recovery. We sampled the same individuals before, during and after SARS-CoV-2 infection to model their specific immune response dynamics while removing donor variability. We observed that COVID-19 CVID patients show defective canonical NF-κB pathway activation and dysregulated expression of BCR-related genes in naïve B cells, as well as enhanced cytotoxic activity but incomplete cytokine response in NK and T cells. Moreover, monocytes from COVID-19 CVID patients show persistent activation of several inflammasome-related genes, including the pyrin and NLRC4 inflammasomes. Our results shed light on the molecular basis of the prolonged clinical manifestations observed in these immunodeficient patients upon SARS-CoV-2 infection, which might illuminate the development of tailored treatments for COVID-19 CVID patients.

Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines (preprint)

COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about the epigenetic alterations that occur in these cells during hyperinflammatory responses in severe COVID-19 patients. In this study, we obtained the DNA methylome and transcriptome of peripheral blood monocytes from severe COVID-19 patients. DNA samples extracted from CD14+CD15- monocytes of 48 severe COVID-19 patients and 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. In parallel, single-cell transcriptomics of 10 severe COVID-19 patients were generated. CellPhoneDB was used to infer changes in the crosstalk between monocytes and other immune cell types. We observed DNA methylation changes in CpG sites associated with interferon-related genes and genes associated with antigen presentation, concordant with gene expression changes. These changes significantly overlapped with those occurring in bacterial sepsis, although specific DNA methylation alterations in genes specific to viral infection were also identified. We also found these alterations to comprise some of the DNA methylation changes occurring during myeloid differentiation and under the influence of inflammatory cytokines. A progression of DNA methylation alterations in relation to the Sequential Organ Failure Assessment (SOFA) score was found to be related to interferon-related genes and T-helper 1 cell cytokine production. CellPhoneDB analysis of the single-cell transcriptomes of other immune cell types suggested the existence of altered crosstalk between monocytes and other cell types like NK cells and regulatory T cells. Our findings show the occurrence of an epigenetic and transcriptional reprogramming of peripheral blood monocytes, which could be associated with the release of aberrant immature monocytes, increased systemic levels of pro-inflammatory cytokines, and changes in immune cell crosstalk in these patients.

Finding answers to COVID-19-specific questions: An information retrieval system based on latent keywords and adapted TF-IDF

The scientific community has reacted to the COVID-19 outbreak by producing a high number of literary works that are helping us to understand a variety of topics related to the pandemic from different perspectives. Dealing with this large amount of information can be challenging, especially when researchers need to find answers to complex questions about specific topics. We present an Information Retrieval System that uses latent information to select relevant works related to specific concepts. By applying Latent Dirichlet Allocation (LDA) models to documents, we can identify key concepts related to a specific query and a corpus. Our method is iterative in that, from an initial input query defined by the user, the original query is expanded for each subsequent iteration. In addition, our method is able to work with a limited amount of information per article. We have tested the performance of our proposal using human validation and two evaluation strategies, achieving good results in both of them. Concerning the first strategy, we performed two surveys to determine the performance of our model. For all the categories that were studied, precision was always greater than 0.6, while accuracy was always greater than 0.8. The second strategy also showed good results, achieving a precision of 1.0 for one category and scoring over 0.7 points overall.

SARS-CoV-2 Viremia Precedes an IL6 Response in Severe COVID-19 Patients: Results of a Longitudinal Prospective Cohort

Background Interleukin 6 (IL6) levels and SARS-CoV-2 viremia have been correlated with COVID-19 severity. The association over time between them has not been assessed in a prospective cohort. Our aim was to evaluate the relationship between SARS-CoV-2 viremia and time evolution of IL6 levels in a COVID-19 prospective cohort. Methods Secondary analysis from a prospective cohort including COVID-19 hospitalized patients from Hospital Universitario La Princesa between November 2020 and January 2021. Serial plasma samples were collected from admission until discharge. Viral load was quantified by Real-Time Polymerase Chain Reaction and IL6 levels with an enzyme immunoassay. To represent the evolution over time of both variables we used the graphic command twoway of Stata. Results A total of 57 patients were recruited, with median age of 63 years (IQR [53–81]), 61.4% male and 68.4% Caucasian. The peak of viremia appeared shortly after symptom onset in patients with persistent viremia (more than 1 sample with > 1.3 log10 copies/ml) and also in those with at least one IL6 > 30 pg/ml, followed by a progressive increase in IL6 around 10 days later. Persistent viremia in the first week of hospitalization was associated with higher levels of IL6. Both IL6 and SARS-CoV-2 viral load were higher in males, with a quicker increase with age. Conclusion In those patients with worse outcomes, an early peak of SARS-CoV-2 viral load precedes an increase in IL6 levels. Monitoring SARS-CoV-2 viral load during the first week after symptom onset may be helpful to predict disease severity in COVID-19 patients.

Sustainable Development Goals in the COVID-19 Pandemic: A Narrative Review

The present narrative review aimed to analyze the impact of the COVID-19 pandemic on the sustainable development goals (SDGS). This information would allow a better comprehension of the actual state of the SDGS and a more efficient programming in future interventions. To achieve the objective of the study, a consensual and critical review was carried out using both primary sources, such as scientific articles, and secondary sources, such as bibliographic indexes, web pages and databases. The Sustainable Development Goals are a global call to action to end poverty, close the gender gap, protect the planet, and improve the lives of people around the world. In 2015, the United Nations General Assembly adopted 17 goals as part of the 2030 Agenda for Sustainable Development, which sets out a plan to achieve the goals in 15 years. However, the COVID-19 pandemic crisis has been a turning point in the achievement of these goals, due to all its consequences at the political, economic, and socio-cultural levels. This review can be used as a guide for future research and reviews in order to understand the status of each of the SDGs and what actions have been taken and proposed in the aftermath of the pandemic in recent years.

Detection of SARS-CoV-2 and its S and N proteins using surface enhanced Raman spectroscopy† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1ra03481b

The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection. This need has generated a high number of new testing methods aimed at replacing RT-PCR, which is the golden standard for testing. Most of the testing techniques are based on biochemistry methods and require chemicals that are often expensive and the supply might become scarce in a large crisis. In the present paper we suggest the use of methods based on physics that leverage novel nanomaterials. We demonstrate that using Surface Enhanced Raman Spectroscopy (SERS) of virion particles a very distinct spectroscopic signature of the SARS-CoV-2 virus can be obtained. We demonstrate that the spectra are mainly composed by signals from the spike (S) and nucleocapsid (N) proteins. It is believed that a clinical test using SERS can be developed. The test will be fast, inexpensive, and reliable. It is also clear that SERS can be used for analysis of structural changes on the S and N proteins. This will be an example of application of nanotechnology and properties of nanoparticles for health and social related matters. The COVID-19 pandemic demonstrated the critical need for accurate and rapid testing for virus detection.

Multicentric Study on the Effect of Rectal Ozone on COVID-19: the Spanish and Slovakian Experience. (preprint)

Objective: To evaluate the effect of rectal Ozone (O3) in severe COVID-19 pneumonia in two different cohorts differing in location (Madrid vs Zilina), ethnicity (Slovakian vs Spanish cohorts) and age. Material and Methods: In a multicenter-study, 32 severe bilateral-COVID-19-pneumonia patients and (+) RT-PCR (reverse transcriptase polymerase chain reaction) SARS-CoV-2 were evaluated (16 from each cohort). Primary outcomes: a) clinical (O2-saturation); b) biochemical (Lymphocyte-count, Fibrinogen, D-Dimer, Urea, Ferritin, LDH [lactate dehydrigenase], IL-6 and CRP [c-reactive protein]); and c) radiological improvement. Secondary outcomes: a) days-of-hospitalization, b) mortality-rate before discharge. The Ozone-protocol consisted of 10 sessions of intra-rectal Ozone, total dose 5.25 mg (150 mL volume, 35 g/ml concentration). The Standard-of-care protocol included O2 supply, antivirals (Remdesivir / Isoprinosine), corticosteroids (Dexamethasone / Metilprednisolone), monoclonal antibodies (Anakinra / Tocilizumab), antibiotics (Azytromicine), anticoagulants (Enoxaparine / Fraxiparine). Protocol was approved by Health Care Ethics Committee (Report 15/4/2020) of our Hospital and by Ethics Committee for Medical Investigation of La Princesa’s Hospital (ACTA CEIm 12/20, 28/5/20, Registry 4146). Results: Patients in Slovakian cohort were younger (53.38 vs 84.69 years). Grade of severity was worse in Spanish-cohort (4.78 vs 3.30 points). Length of stay was superior in Spanish-cohort (27.38 vs 10.07 days). Both cohorts improved O2-saturation and Lymphocyte-count. Inflammation biomarkers (Fibrinogen, D-Dimer, Urea, Ferritin, LDH, CRP and IL-6) decreased in both cohorts. In Spanish-cohort, Urea and Ferritin improvement was not significant (p>0.05), while in Slovakian-cohort, Urea, Fibrinogen and LDH were not significant (p>0.05) Radiological signs of bilateral pneumonitis decreased on both cohorts. Mortality was similar (12.5%). Conclusion: After Standard of care protocol, Rectal Ozone improved O2-saturation, decreased inflammation biomarkers and improved Taylor’s radiological scale in both cohorts. Although age, grade of severity and days of hospitalization were inferior in Slovakian cohort, mortality was similar in both cohorts, but inferior if compared to an external control cohort.

Transcriptomic clustering of critically ill COVID-19 patients (preprint)

Infections caused by SARS-CoV-2 may cause a severe disease, termed COVID-19, with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms, and their modulation is the only therapeutic strategy that has shown a mortality benefit. Herein, we used peripheral blood transcriptomes of critically-ill COVID-19 patients obtained at admission in an Intensive Care Unit (ICU), to identify two transcriptomic clusters characterized by expression of either interferon-related or immune checkpoint genes, respectively. These profiles have different ICU outcome, in spite of no major clinical differences at ICU admission. A transcriptomic signature was used to identify these clusters in an external validation cohort, yielding similar results. These findings reveal different underlying pathogenetic mechanisms and illustrate the potential of transcriptomics to identify patient endotypes in severe COVID-19, aimed to ultimately personalize their therapies.

Personality Traits, Cognitive Styles, Coping Strategies, and Psychological Impact of the COVID-19 Pandemic Lockdown on Healthy Youngsters.

The objective of the present study was to explore possible changes in the psychological wellbeing of young healthy students during the initial 14 days of the COVID-19 general lockdown that occurred in March of 2020, and if there was any relation with specific personality traits (neuroticism, psychoticism, and extraversion), cognitive styles (internal and external locus of control and intolerance of uncertainty), and coping strategies. One hundred twenty-two university students aged from 18 to 29 years participated in the study. The dispositional factors were assessed at the beginning of the study, while measures of psychological adjustment (anxiety, depression, and self-perceived health) were taken in three different assessment stages, employing validated questionnaires and scales. Anxiety and depression scores significantly increased after one week of lockdown, reaching a plateau pattern by the second week. The levels of self-perceived mental health, vitality, and quality of life showed a pattern of sustained progressive decrease, with a more acute lessening during the first week. Neuroticism, intolerance of uncertainty, and negative autofocus were associated to worse levels of psychological adjustment. These individual differences might be taken into consideration when designing prevention programs aiming to dampen the psychological impact of a general lockdown in healthy population.

Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents (preprint)

As SARS-CoV-2 continues to spread globally, questions have emerged regarding the strength and durability of immune responses in specific populations. In this study, we evaluated humoral immune responses in 69 children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection. We detected robust IgM, IgG, and IgA antibody responses to a broad array of SARS-CoV-2 antigens at the time of acute infection and 2 and 4 months after acute infection in all participants. Notably, these antibody responses were associated with virus neutralizing activity that was still detectable 4 months after acute infection in 94% of children. Moreover, antibody responses and neutralizing activity in sera from children and adolescents were comparable or superior to those observed in sera from 24 adults with mild symptomatic infection. Taken together, these findings indicate children and adolescents with mild or asymptomatic SARS-CoV-2 infection generate robust and durable humoral immune responses that are likely to protect from reinfection.

ATTENTION TO DIVERSITY DURING COVID-19: LEGISLATIVE REVIEW OF MEASURES ACCORDING TO LOMCE

Tras el establecimiento del estado de alarma provocado por la COVID-19 y, el consiguiente cierre de los centros educativos a nivel nacional, la educación formal se ha trasladado de un contexto de enseñanza presencial a entornos virtuales de aprendizaje en cuestión de horas. En este trabajo, presentamos una revisión de la normativa educativa española sobre la atención a la diversidad del alumnado y de las medidas a aplicar en contextos extraordinarios de aprendizaje, como el que vivimos a nivel mundial. Para su realización, hemos realizado un análisis de los contenidos, centrado en las medidas de atención a la diversidad existentes en la legislación orgánica nacional y en las directrices de aplicación del Ministerio de Educación y Formación Profesional. Las políticas educativas, y las administraciones responsables, no se encuentran preparadas para un cambio en la metodología de atención al alumnado, que incida en la disminución de las desigualdades del alumnado y proporcione un acceso equitativo al aprendizaje, ya que el rol compensador de la escuela (como institución) no puede suplirse a través de la virtualización de la enseñanza. En este aspecto, los docentes y la autonomía de los centros suponen un valor añadido en la igualdad de oportunidades, el cual se ve disminuido en entornos virtuales educativos por las condiciones socioeconómicas del alumnado, aumentando la desigualdad educativaAlternate abstract:Depois do estabelecimento do estado de alarme provocado pela COVID-19 e, o consequente fechamento dos centros educativos a nivel nacional, a educaçao formal foi transformada de um contexto de ensino presencial para entornos virtuais de aprendizado em questăo de horas. Neste trabalho, apresentamos uma revisăo da normativa educativa espanhola sobre a atençao a diversidade dos estudantes e das medidas a serem aplicadas em contextos extraordinarios de aprendizagem, como este que vivemos a nivel mundial. Para sua realizaçao, fizemos uma análise dos conteúdos, focando nas medidas de atençao a diversidade existentes na legislaçao orgánica nacional e nas diretrizes de aplicaçao do Ministério de Educaçao e Formaçao Profissional. As políticas educativas, e os entes responsáveis, năo estăo preparadas para uma mudança na metodologia de atençao aos alunos, que implique a diminuiçao das desigualdades dos alunos e proporcione um acceso equitativo ao aprendizado, já que o papel compensador da escola (como instituiçâo) năo pode ser fornecido através da virtualizaçâo do ensino. Nesse aspecto, os professores e a autonomia dos centros tém um valor adicionado na igualdade das oportunidades, o que se ve diminuido em entornos virtuais educativos pelas condiçöes socioeconómicas dos alunos, aumentando a desigualdade educativa.Alternate abstract:Following the establishment of the state of alarm caused by COVID-19 and the consequent closure of schools nationwide, formal education has moved from a presential learning context to virtual learning environments in a matter of hours. We present a review of the Spanish educational regulations on attention to students' diversity and the measures to be implemented in extraordinary learning contexts, such as the one we live worldwide. For its realization, we have conducted an analysis of the content embodied in the national organic legislation and in the guidelines of the Education and Vocational Training Ministry, focused on the measures for attention to diversity. The educational policy, and administrations in charge, are not prepared for a change in the methodology of attention to students that can reduce inequalities among students and provide an equitable access to learning, since the compensatory role of the school (as institution) cannot be supplied through the virtualization of teaching. In this regard, teachers and the autonomy of the centers represent an added value in equal opportunities, which is diminished in virtual educational environments due to the socioeconomic conditions of students, further increasing educational inequality

Age-related changes in the upper respiratory microbiome are associated with SARS-CoV-2 susceptibility and illness severity (preprint)

Children are less susceptible to SARS-CoV-2 and typically have milder illness courses than adults. We studied the nasopharyngeal microbiomes of 274 children, adolescents, and young adults with SARS-CoV-2 exposure using 16S rRNA gene sequencing. We find that higher abundances of Corynebacterium species are associated with SARS-CoV-2 infection and SARS-CoV-2-associated respiratory symptoms, while higher abundances of Dolosigranulum pigrum are present in SARS-CoV-2-infected individuals without respiratory symptoms. We also demonstrate that the abundances of these bacteria are strongly, and independently, associated with age, suggesting that the nasopharyngeal microbiome may be a potentially modifiable mechanism by which age influences SARS-CoV-2 susceptibility and severity.

Introduction: Nodes in global networks

The on-going COVID-19 crisis demonstrates how interlinked and networked our globalized society has become. Overall, the special issue advances our knowledge of nodes in global networks by further investigating the particularities of such nodes, drawing conclusions on both the nodes themselves and the networks they are involved in. Yet, there are also examples of gateway cities serving as engines of peripheral growth (Scholvin, 2017), which indicates that considerably more research is needed to fully understand nodes in global networks from this particular angle. These functions are not necessarily additive, meaning that gateways are diverse - both in terms of the role they play in global networks and regarding their spatial range (Breul, 2019;Breul & Revilla Diez, 2017;Scholvin, 2020a). [Extracted from the article] Copyright of Growth & Change is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)