Use of water from small alluvial aquifers for irrigation in semi-arid regions.

Water from small alluvial aquifers constitutes an attractive and low-cost option for irrigation and rural development in Northeastern Brazil. Based on piezometric measurements, geochemical analyses and electrical conductivity estimates, the present case study identified the main processes determining the hydrosaline dynamics of an alluvial aquifer in a small watershed inserted in the crystalline bedrock of a semi-arid region in Ceará and evaluated the availability of water for irrigation. Accumulation of salts in soil are related to evaporative flux from the aquifer and is increased by irrigation from the groundwater of the alluvial aquifer. The water in these aquifers may be used for irrigation, but represents a risk of soil salinization and alkalinization. Integrated management of surface and underground water resources in the Forquilha watershed may help control irrigation water quality (salinity and residual alkalinity), thereby rationalizing the use of local reservoirs and minimizing losses from evaporation. It has to take into account the complex dynamic of salts and water between the reservoirs, release of water into the river, floods and irrigations

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

Exploration des mécanismes de résistance du virus de l'hépatite B (VHB) à l’entécavir avec une approche phénotypique

Treatment of chronic hepatitis B (HBV) relies on two antivirals, tenofovir and entecavir. These treatments block HBV DNA replication, thus preventing complications such as cirrhosis and hepatocellular carcinoma. Treatment failures are rare (<1 % for entecavir) but require evaluation of patient adherence to medication and identification of resistance mutations in the viral polymerase. In a subset of patients, these mutations are not detected and treatment failure remains unexplained. We hypothesized that new mechanisms of resistance to entecavir could be identified in these patients using an integrative approach, based on phenotypic testing.This approach lead to the identification of mutation rt250L, associated with entecavir treatment failure in vivo and in vitro, even in the absence of other entecavir resistance mutations. Whole HBV genome analysis using deep sequencing suggested that immune-escape associated mutations could be associated with an increased risk of partial viral response to entecavir, especially in immunocompromised patients.Le traitement de l’infection chronique par le virus de l’hépatite B (VHB) repose notamment sur l’entécavir. Cet antiviral permet de prévenir efficacement les complications que sont la cirrhose et le carcinome hépatocellulaire. Les échecs de traitement sont rares mais ils doivent faire rechercher une mésobservance et/ou la sélection de mutations de résistance dans la polymérase du VHB. Chez certains patients, aucune mutation de résistance connue n’est détectée et l’échec reste inexpliqué. Nous avons émis l’hypothèse que ces situations d’échecs inexpliqués de traitement à l’entécavir pourraient être associées à de nouveaux mécanismes de résistance, identifiables par une approche transversale basée sur un test phénotypique de résistance.Cette approche a mis en évidence le rôle majeur et sous-estimé de la mutation rt250L dans la résistance à l’entécavir in vitro et in vivo. L’étude du génome entier du VHB a montré que les mutations d’échappement à la réponse immunitaire pourraient être associées à certains échecs de traitement par entécavir, notamment chez les patients immunodéprimés

Mechanisms of HBV resistance to entecavir explored using a phenotypic approach

L’exploration des échecs de traitement par entécavir des hépatites B chroniques repose sur l’évaluation de l’observance thérapeutique et sur la recherche de mutations de résistance dans le domaine polymérase/transcriptase inverse (Pol/RT) du VHB (Lampertico et al., 2017). Chez certains patients, cet examen n’est pas informatif car il ne permet pas de détecter de mutation de résistance connue à l’entécavir. Nous avons émis l’hypothèse que ces situations d’échecs inexpliqués de traitement à l’entécavir pourraient être associées à de nouveaux mécanismes de résistance, identifiables par des approches phénotypiques.Dans la première partie de ce travail, nous avons développé une approche transversale d’analyse de la résistance combinant des tests génotypiques, phénotypiques et un suivi pharmacologique. Cette approche a été appliquée à 9 patients en échec de traitement par entécavir et infectés par des isolats de sensibilité diminuée à cet antiviral. L’approche phénotypique a permis de montrer dans ce contexte que la mutation rt250L suffisait à conférer une résistance l’entécavir in vitro et in vivo, tandis que la mutation rt173L n’avait pas d’impact sur le niveau de résistance (Marlet et al., 2020). Ces résultats contribueront à la réévaluation des recommandations d’interprétation du génotypage de résistance du VHB.La seconde partie de ce travail visait à explorer les mécanismes impliqués dans les échecs de traitement par entécavir en l’absence de mutation de résistance détectable dans le domaine Pol/RT. Cette étude a porté sur 3 patients en réponse virologique partielle à l’entécavir après réactivation du VHB dans le cadre d’un traitement immunosuppresseur. Chez ces patients, les mutations sélectionnées sur l’ensemble du génome du VHB avant et pendant le traitement par entécavir ont été recherchées par séquençage profond. Chez deux patients, des mutations d’échappement au système immunitaire ont été sélectionnées avant traitement dans l’Ag HBs. Chez un troisième patient, deux mutations ont été sélectionnées durant le traitement par entécavir dans des domaines associés à la réponse immunitaire (Q120K, pre-S2) et à la morphogenèse (Q206K, Core), sans conférer de résistance. Ces mutations en dehors du domaine Pol/RT pourraient avoir contribué indirectement à la réponse virologique partielle, notamment par échappement à la réponse immunitaire déjà déficiente chez ces patients immunodéprimés. Ces résultats suggèrent que la recherche et la caractérisation phénotypique de mutations sélectionnées en dehors du domaine Pol/RT pourraient permettre de mieux comprendre les mécanismes de réponse virologique partielle à l’entécavir.Treatment adaptation after hepatitis B virus (HBV) entecavir treatment failure relies on evaluation of patient adherence to treatment and identification of resistance mutations by sequencing of the polymerase/reverse transcriptase domain (Pol/RT) (Lampertico et al., 2017). In a subset of patients, these mutations are not detected and treatment failure remains unexplained. We hypothesized that these observed discrepancies may be linked to other mechanisms of resistance, which can be detected with an integrative approach, based on a phenotypic resistance assay.In the first part of this work, this approach was retrospectively applied to nine clinical isolates associated with entecavir treatment failure and harboring mutations conferring a reduced susceptibility to entecavir. Mutation rt250L, but not rt173L, was associated with resistance to entecavir in vitro and in vivo, even in the absence of other entecavir resistance mutations (Marlet et al., 2020). These results will be useful for future update of genotypic drug resistance testing guidelines.In the second part of this work, we aimed to explore the mechanisms associated with entecavir treatment failure in the absence of detectable resistance mutations by Pol/RT Sanger sequencing. Using deep sequencing, we retrospectively explored the whole HBV genome of three clinical isolates associated with partial virological response to entecavir in immunocompromised patients. HBs Ag immune escape mutations were selected before treatment in two patients. In a third, mutations were selected during entecavir treatment in domains associated with immune response (Q120K, pre-S2) and morphogenesis (Q206K, Core), without conferring any resistance to entecavir. We hypothesized that these mutations could increase the risk of partial virological response to entecavir by an immune escape mechanism, especially in immunocompromised patients. Identification and characterization of mutations selected outside of the Pol/RT domain during entecavir treatment could be useful for a better understanding of viral factors associated with partial virological response to entecavir

Comparison of Lumipulse® G1200 with Kryptor and Modular E170 for the measurement of 7 tumor markers

"This is the pre-peer reviewed version of the following article: "Comparison of LUMIPULSE® G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers", which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/jcla.21802/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."Background: Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9 and Cyfra 21-1.Methods: 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse G1200 and either Kryptor (for AFP) or Modular (for the six other markers). Results: The good precision of Lumipulse G1200 assays was confirmed with CVs 95% and tumor marker kinetics were all similar.Conclusion: We confirmed the analytical performances of Lumipulse tumor marker assays except the CYFRA 21-1 assay, which performances were not acceptable in this study. Also, we demonstrated that 5 out of 7 tumor markers assays results (PSA, AFP, CA 125, CA 15-3, CYFRA 21-1) are directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual replacement of one system by another

Rapid SARS-CoV-2 inactivation by mercury and LED UV-C lamps on different surfaces

International audienceSARS-CoV-2 remains infectious for several hours on surfaces. It can be inactivated by UV-C irradiation but optimal conditions for rapid inactivation, especially on non-plastic surfaces remains unclear. A SARS-CoV-2 inoculum was irradiated with a UV-C LED (265 nm) or a UV-C mercury lamp (254 nm). Infectivity titers (TCID50/mL) and inactivation rates were then quantified on plastic, steel, tissue, paper and cardboard surfaces. We demonstrated that efficient SARS-CoV-2 inactivation (> 99.999% on plastic and steel, ≥ 99.8% on tissue, paper and cardboard) can be achieved by both a UV-C mercury lamp and a UV-C LED after 30 s of irradiations at 3 cm, corresponding to UV-C doses of 92.85 and 44.7 mJ/cm2, respectively. Inactivation on a plastic surface was more efficient with the mercury UV-C lamp (p < 0.005). The mercury UV-C lamp could be more relevant than the LED in high-risk settings, such as medical care or research laboratories

Antigène HBs positif en l'absence de toute infection par le virus de l'hépatite B : la face 1 cachée de l'Ag HBs

International audienceFrench recommendations for the screening of hepatitis B virus (HBV) infection were updated in 2019 with the association of three markers: HBs Ag, anti-HBs Ab and anti-HBc Ab. These three markers allow identification of infected patients, vaccinated patients and patients who have been in contact with HBV. A positive HBs Ag is usually associated with HBV infection but this interpretation must take into account the clinical context. In particular, the absence of anti-HBc Ab, normal ALAT levels and the absence of jaundice can be associated with recent HBV vaccination or false-positive HBs Ag. Recent HBV vaccination can usually be confirmed by patient questioning, while confirmatory tests are useful to detect false positive HBs Ag. If necessary, a second sample can be requested to confirm the interpretation.La stratégie de dépistage d'une infection par le virus de l'hépatite B (VHB) a évolué 8 en 2019 avec la recherche systématique de l'Ag HBs, des Ac anti-HBs et des Ac anti-HBc. Ces 9 trois marqueurs permettent d'identifier les patients infectés par le VHB, les patients vaccinés 10 contre le VHB, ceux ayant eu un contact avec le VHB et ceux n'ayant jamais été en contact 11 avec le VHB. Pour prévenir toute erreur d'interprétation, la conclusion de la sérologie VHB 12 doit tenir compte du contexte clinico-biologique. Dans le cas particulier d'un Ag HBs positif, 13 il faudra évoquer en première intention une infection par le VHB. En seconde intention, 14 notamment en l'absence d'Ac anti-HBc, de cytolyse hépatique et d'ictère, il faudra évoquer la 15 possibilité d'une vaccination VHB récente, d'un Ag HBs faux positif voire d'une infection 16 débutante. L'interrogatoire permet de révéler une vaccination récente tandis qu'un Ag HBs 17 faussement positif peut être détecté avec un test de confirmation de l'Ag HBs. Si nécessaire, un 18 contrôle sérologique après 2 à 3 semaines peut être réalisé pour confirmer ou infirmer 19 l'infection par le VHB