Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

SignificanceThere is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged 4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute; The Rockefeller University; the St. Giles Foundation; the NIH (Grants R01AI088364 and R01AI163029); the National Center for Advancing Translational Sciences; NIH Clinical and Translational Science Awards program (Grant UL1 TR001866); a Fast Grant from Emergent Ventures; Mercatus Center at George Mason University; the Yale Center for Mendelian Genomics and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (Grants UM1HG006504 and U24HG008956); the Yale High Performance Computing Center (Grant S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the JPB Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (Grant ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (Grant ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM) (Grant EQU201903007798); the French Agency for Research on AIDS and Viral hepatitis (ANRS) Nord-Sud (Grant ANRS-COV05); the ANR GENVIR (Grant ANR-20-CE93-003), AABIFNCOV (Grant ANR-20-CO11-0001), CNSVIRGEN (Grant ANR-19-CE15-0009-01), and GenMIS-C (Grant ANR-21-COVR-0039) projects; the Square Foundation; Grandir–Fonds de solidarité pour l’Enfance; the Fondation du Souffle; the SCOR Corporate Foundation for Science; The French Ministry of Higher Education, Research, and Innovation (Grant MESRI-COVID-19); Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM; and the University Paris Cité. P. Bastard was supported by the FRM (Award EA20170638020). P. Bastard., J.R., and T.L.V. were supported by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt Schueller). Work at the Neurometabolic Disease lab received funding from Centre for Biomedical Research on Rare Diseases (CIBERER) (Grant ACCI20-767) and the European Union's Horizon 2020 research and innovation program under grant agreement 824110 (EASI Genomics). Work in the Laboratory of Virology and Infectious Disease was supported by the NIH (Grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1), a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Infanta Leonor University Hospital supported the research of the Department of Internal Medicine and Allergology. The French COVID Cohort study group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (Grant RECOVER WP 6). This work was also partly supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research, NIH (Grants ZIA AI001270 to L.D.N. and 1ZIAAI001265 to H.C.S.). This program is supported by the Agence Nationale de la Recherche (Grant ANR-10-LABX-69-01). K.K.’s group was supported by the Estonian Research Council, through Grants PRG117 and PRG377. R.H. was supported by an Al Jalila Foundation Seed Grant (Grant AJF202019), Dubai, United Arab Emirates, and a COVID-19 research grant (Grant CoV19-0307) from the University of Sharjah, United Arab Emirates. S.G.T. is supported by Investigator and Program Grants awarded by the National Health and Medical Research Council of Australia and a University of New South Wales COVID Rapid Response Initiative Grant. L.I. reports funding from Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”). This research was partially supported by the Instituto de Salud Carlos III (Grant COV20/0968). J.R.H. reports funding from Biomedical Advanced Research and Development Authority (Grant HHSO10201600031C). S.O. reports funding from Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development (Grant JP20fk0108531). G.G. was supported by the ANR Flash COVID-19 program and SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University iCOVID programs. The 3C Study was conducted under a partnership agreement between INSERM, Victor Segalen Bordeaux 2 University, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also supported by the Caisse Nationale d’Assurance Maladie des Travailleurs Salariés, Direction générale de la Santé, Mutuelle Générale de l’Education Nationale, Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Program “Cohortes et collections de données biologiques.” S. Debette was supported by the University of Bordeaux Initiative of Excellence. P.K.G. reports funding from the National Cancer Institute, NIH, under Contract 75N91019D00024, Task Order 75N91021F00001. J.W. is supported by a Research Foundation - Flanders (FWO) Fundamental Clinical Mandate (Grant 1833317N). Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. Work at Vall d’Hebron was also partly supported by research funding from Instituto de Salud Carlos III Grant PI17/00660 cofinanced by the European Regional Development Fund (ERDF/FEDER). C.R.-G. and colleagues from the Canarian Health System Sequencing Hub were supported by the Instituto de Salud Carlos III (Grants COV20_01333 and COV20_01334), the Spanish Ministry for Science and Innovation (RTC-2017-6471-1; AEI/FEDER, European Union), Fundación DISA (Grants OA18/017 and OA20/024), and Cabildo Insular de Tenerife (Grants CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). T.H.M. was supported by grants from the Novo Nordisk Foundation (Grants NNF20OC0064890 and NNF21OC0067157). C.M.B. is supported by a Michael Smith Foundation for Health Research Health Professional-Investigator Award. P.Q.H. and L. Hammarström were funded by the European Union’s Horizon 2020 research and innovation program (Antibody Therapy Against Coronavirus consortium, Grant 101003650). Work at Y.-L.L.’s laboratory in the University of Hong Kong (HKU) was supported by the Society for the Relief of Disabled Children. MBBS/PhD study of D.L. in HKU was supported by the Croucher Foundation. J.L.F. was supported in part by the Evaluation-Orientation de la Coopération Scientifique (ECOS) Nord - Coopération Scientifique France-Colombie (ECOS-Nord/Columbian Administrative department of Science, Technology and Innovation [COLCIENCIAS]/Colombian Ministry of National Education [MEN]/Colombian Institute of Educational Credit and Technical Studies Abroad [ICETEX, Grant 806-2018] and Colciencias Contract 713-2016 [Code 111574455633]). A. Klocperk was, in part, supported by Grants NU20-05-00282 and NV18-05-00162 issued by the Czech Health Research Council and Ministry of Health, Czech Republic. L.P. was funded by Program Project COVID-19 OSR-UniSR and Ministero della Salute (Grant COVID-2020-12371617). I.M. is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies (PID); by the Katholieke Universiteit Leuven C1 Grant C16/18/007; by a Flanders Institute for Biotechnology-Grand Challenges - PID grant; by the FWO Grants G0C8517N, G0B5120N, and G0E8420N; and by the Jeffrey Modell Foundation. I.M. has received funding under the European Union’s Horizon 2020 research and innovation program (Grant Agreement 948959). E.A. received funding from the Hellenic Foundation for Research and Innovation (Grant INTERFLU 1574). M. Vidigal received funding from the São Paulo Research Foundation (Grant 2020/09702-1) and JBS SA (Grant 69004). The NH-COVAIR study group consortium was supported by a grant from the Meath Foundation.Peer reviewe

Evolución geoquímica del domo cerro La Torta, El Tatio, a través de inclusiones vítreas

Memoria para optar al título de GeólogaEl Cerro La Torta es un domo volcánico riolítico, de 34 ka de edad, ubicado en la zona de El Tatio, al oeste de los Cerros de Tocorpuri, en la frontera con Bolivia, a 1270 km al noreste de Santiago y 100 km al este de Calama. Abarca un área de 12 km2 y un volumen de 4,7 km3 a una altura de 5090 m s.n.m. El objetivo principal de este estudio es reconstruir los procesos ígneos que ocurrieron en evolución del magma que formó el Cerro La Torta mediante inclusiones vítreas. Para esto se realizaron análisis en microsonda electrónica y ablación láser luego de un detallado trabajo de petrografía de inclusiones vítreas hospedadas en anfíbol y plagioclasa. El domo Cerro la Torta erupcionó a partir de un magma riolítico, rico en potasio y con un 74,5% wt de sílice desde una fuente magmática que cristalizó a presiones de entre 114 y 185 MPa, equivalentes a profundidades entre los 90 y 2390 m. bajo el nivel del mar. La temperatura de cristalización de las distintas fases y sus respectivas inclusiones varía entre 949 y 723 °C en promedio. La fugacidad de oxígeno del fundido (logfO2) es -12,3, indicando un ambiente oxidante, y el porcentaje de agua del fundido, 4,9% wt. A pesar de los datos anteriores, las inclusiones estudiadas registran un último evento de cristalización de fases minerales debido a que un magma de 74% de sílice no puede fraccionar piroxeno, por lo que la fuente real está más profunda y menos diferencia. La gran presencia de andesina indica que este magma parental real, es andesítico. Se establecen dos modelos de fuente magmática para La Torta. i) Fuente magmática más profunda que los 2,6 km de espesor, que en un principio (0,8 Ma) tenía composición andesítica a dacítica, erupcionando el volcán Tocorpuri y, posteriormente, los Cerros de Tocorpuri. ii) Fuente magmática netamente riolítica alimentada por otra más profunda y primitiva. Este magma contenía enstatita y magnesio-hornblenda que por un calentamiento provocado por otro cuerpo magmático más primitivo se disolvieron violentamente, enriqueciendo el sistema en Ni, Cr y tierras raras pesadas, quedando escasos micro-fenocristales de enstatita. Las nuevas fases de Mg.-Hbl asimilaron estos elementos tanto en su cristal como en sus inclusiones. Posteriormente, el magma fue ascendiendo y cristalizando fraccionadamente a fases minerales como cuarzo y biotita, registrando un decaimiento en la concentración de los elementos compatibles de las inclusiones de centro a borde. Luego de un periodo de residencia suficiente para formar fenocristales de hasta un cm de largo, ocurre una descompresión y recalentamiento debido a la fuente de calor aportada por el APMB, que creó las texturas de reabsorción en cuarzo y anfíbol

Induction of direct organogenesis from aerial explants of scented alstroemeria genotypes

Alstroemeria is an important pot plant and cut flower in the ornamental plant market, and its propagation mainly occurs by rhizome division. However, this method is inefficient and time-consuming and may contribute to the spread of viruses. This study focused on developing in vitro propagation protocols using aerial explants of Alstroemeria caryophyllaea and A. ‘Sweet Laura’, two scented genotypes. Aerial explants of alstroemeria were regenerated by testing three types of aerial explants and four concentrations of cytokinins. Both A. caryophyllaea and A. ‘Sweet Laura’ showed the highest induction rate from shoots, with values of 35 and 63.3%, respectively. For both genotypes, the optimum BAP concentration for direct organogenesis from buds was 1.0 mg L-1. Finally, a successful protocol for in vitro propagation of A. caryophyllaea and A. ‘Sweet Laura’ through direct organogenesis from aerial explants was generated.Alstroemeria es una especie importante en el mercado de plantas ornamentales y flores de corte y su propagación es principalmente realizada por división de rizomas. Sin embargo, este método es ineficiente, altamente demandante de tiempo y puede contribuir a la dispersión de virus. Este estudio tuvo como objetivo desarrollar un protocolo de propagación in vitro usando explantes aéreos de Alstroemeria caryophyllaea y A. cv. ‘Sweet Laura’, dos genotipos aromáticos. Los explantes aéreos de alstroemeria fueron regenerados probando tres tipos de explantes y cuatro concentraciones de citoquininas. Tanto A. caryophyllaea como A. cv. ‘Sweet Laura’ mostraron la mayor tasa de inducción desde brotes, con valores de 35 y 63,3%, respectivamente. Para ambos genotipos la concentración óptima de BAP para desarrollar organogénesis directa desde brotes fue de 1.0 mg L-1. Finalmente, se generó un protocolo exitoso para la propagación in vitro de A. caryophyllaea y A. cv. ‘Sweet Laura’ a partir de explantes aéreos

Role of flower preservative solutions during postharvest of Hydrangea macrophylla cv. Bela

D. Aros, C. Silva, C. Char, L. Prat, and V. Escalona. 2016. Role of flower preservative solutions during postharvest of Hydrangea macrophylla cv. Bela. Cien. Inv. Agr. 43(3):418-428. Hydrangea macrophylla (hydrangea) is widely used as an ornamental plant and cut flower due to its inflorescence, which is composed of colored bracts. As cut flowers, hydrangeas show a postharvest life of up to 1 month at 2 °C, but little is known about their postharvest life during air shipment. This study was aimed at evaluating the effect of Triton X-100 (surfactant) and ClO2 (biocide) during an air shipment simulation of hydrangea harvested at two floral stages of development: fresh and antique. Vase life, fresh weight loss (FWL) and solution uptake were evaluated after an air shipment simulation. Furthermore, bacterial counts and microscopic observation of the bracts were performed in order to understand the water relations of hydrangea during vase life. The longest vase life was observed in antique hydrangeas, and the control (deionized water) was the best treatment, reaching up to 32.7 days in this floral stage. FWL was faster when using Triton X-100 (3.83 days to lose 20% of FW) compared to deionized water (8.75 days). However, this flower preservative was efficient at promoting solution uptake (31.96 mL). Bacterial plugging did not appear to occur considering that the high presence of microorganisms counted did not affect solution uptake or vase life. The presence of stomata on the bracts seems to be crucial for the dehydration of the inflorescence, a problem that was not solved by the higher water uptake promoted by Triton X-100. Thus, deionized water was the best treatment, and the effect of flower preservatives in order to extend vase life of hydrangea cut flowers was insignificant

Identification of volatile compounds associated with the aroma of white strawberries (Fragaria chiloensis)

Artículo de publicación ISIBACKGROUND: Fragaria chiloensis (L.) Mill spp. chiloensis form chiloensis, is a strawberry that produces white fruits with unique aromas. This species, endemic to Chile, is one of the progenitors of Fragaria x ananassa Duch. In order to identify the volatile compounds that might be responsible for aroma, these were extracted, and analyzed by gas chromatography–mass spectrometry (GC-MS), gas chromatography–olfactometry (GC-O) and compared with sensory analyses. RESULTS: Threemethods of extractionwere used: solvent-assisted evaporation (SAFE), headspace solid phasemicro-extraction (HS-SPME) and liquid–liquid extraction (LLE). Ninety-nine volatile compounds were identified by GC-MS, of which 75 showed odor activity using GC-O. Based on the highest dilution factor (FD=1000) and GC-O intensity ≥2, we determined 20 major compounds in white strawberry fruit that contribute to its aroma.We chose 51 compounds to be tested against their commercial standards. The identities were confirmed by comparison of their linear retention indices against the commercial standards. The aroma of white strawberry fruits was reconstituted with a syntheticmixture of most of these compounds. CONCLUSION: The volatile profile of white strawberry fruit described as fruity, green–fresh, floral, caramel, sweet, nutty and woody will be a useful reference for future strawberry breeding programs.This research was supported by Millennium Nucleus in Plant Cell Biotechnology (PCB) ICM P06- 065-F

Blueberries Mycorrhizal Symbiosis Outside of the Boundaries of Natural Dispersion for Ericaceous Plants in Chile

Blueberry culture in Chile has been expanding its acreage from suitable edaphoclimatic conditions to environments in which some soil characteristics depart from blueberries’ requirements, among others, to calcareous soils with pH over 7.5. Under these conditions, specific technological field management is required to keep plants producing fruits; however, little attention has been given to mycorrhizal symbiosis. Several studies have been carried out since 2000 in order to assess the importance of the mycorrhizal symbiosis for cultivated blueberry plants in Mediterranean agroecosystems that do not have native Ericaceous plants. Survey of the mycorrhizal status of commercial blueberry fields and directed inoculation assays with commercial and native mycorrhizal inocula have been conducted. It was observed that under these conditions, field blueberry plants form mycorrhizae with native arbuscular and ectomycorrhizal fungi with a lower infection percentage. In some samples, only arbuscular mycorrhizae were observed. Ericoid mycorrhizae were present to a variable extent, probably as a consequence of contamination at the nursery level. No differences in field plants performance were observed. However, when blueberry plants growing in containers, are inoculated with mycorrhizal fungi at the nursery, the symbiosis performs with different levels of efficiency, from positive to negative when compared to non-inoculated plants, but having native mycorrhizal fungi. In some experiments, ericoid mycorrhiza produced by Hymenosyphus ericae had lower plants’ biomass (dwt) compared with native mycorrhiza, but in others, they had the highest. The significance of the fungal edaphic adaptation is discussed

Contexto sociocultural y su influencia en el uso y manejo del lenguaje

Tesis (Psicopedagogo, Licenciado en Educación)El motivo de estudio de nuestra investigación, surge a lo largo de las experiencias adquiridas a través de las prácticas realizadas durante nuestros años de estudio, en las cuales percibimos aquellos sectores que manifiestan necesidades educativas, culturales y económicas, naciendo desde aquí la inquietud por indagar y clarificar la influencia existente entre contexto sociocultural y el dominio ejercido sobre el uso y manejo lingüístico, refiriéndonos a la estrecha relación e interacción que se produce entre ambos, destacamos cómo estos dos ámbitos se cohesionan y actúan como agentes socializadores. Cómo influyen en que niñas y niños utilicen y manejen el lenguaje. Estos dos factores determinantes, el contexto sociocultural y el lenguaje, son dos importantes y grandes dimensiones; el primero como medio socializador que contiene aspectos como la familia, el barrio y los pares que proveen de experiencias y diversas alternativas, mientras el segundo es un medio eficiente que nos permite acceder a conocimientos fundamentales, expresarnos, comunicarnos, interactuar, compartir experiencias, lograr percibir nuevas visiones de mundo y además culturizarnos, a medida que éstos se relacionen adecuadamente se formarán seres participativos e integrales. Con respecto al planteamiento anterior es posible determinar que nuestro estudio se realizó en un contexto sociocultural medio trabajador, en el cual logramos percibir que el medio no provee de adecuadas instancias para lograr un correcto uso, comprensión y expresión lingüística. Con el fin de elaborar esta investigación de manera adecuada y consistente, ésta se ha estructurado en base a dar a conocer, describir y explicar conceptos y características del contexto sociocultural y la influencia ejercida sobre el lenguaje