Presence of Hypertension Is Reduced by Mediterranean Diet Adherence in All Individuals with a More Pronounced Effect in the Obese: The Hellenic National Nutrition and Health Survey (HNNHS)

Hypertension is a major risk of cardiovascular diseases. This study's aim was to examine associations between hypertension and a priori known lifestyle risk factors, including weight status and Mediterranean diet adherence. The study included a representative sample of the adult population (N = 3775 (40.8% males)), from the Hellenic National Nutrition and Health Survey (HNNHS), which took place from September 2013 to May 2015. Demographic and anthropometric data were collected using validated questionnaires, and blood pressure (BP) measurements were performed for the two main metropolitan areas (N = 1040; 41.1%). Hypertension diagnosis was according to the International Classification of Diseases (ICD-10) guidelines. Weighted proportions, extended Mantel-Haenszel (M-H) analyses, and multiple logistic regressions (for the survey data) were performed. Mean systolic BP (SBP) and diastolic BP (DBP) were 118.6 mmHg and 72.2 mmHg respectively, with both values being higher in males compared to females in all age groups (p < 0.001). Study participants with hyperlipidemia or diabetes, and those overweight, were almost twice as likely to be hypertensives, with the odds increasing to 4 for those obese (p for all, < 0.05). Stricter Mediterranean diet adherence significantly decreased the likelihood of hypertension by 36% (OR: 0.64; 95% CI: 0.439, 0.943), and a significant interaction was found between Mediterranean diet adherence and weight status on hypertension. The presence of hypertension is clustered with comorbidities, but is significantly associated with modifiable risk factors, including Mediterranean diet and weight status, underlining the need for personalized medical nutritional treatment

THINK4JOBS TRAINING: Critical Thinking Training Packages for Higher Education Instructors and Labour Market Tutors

This Report presents the findings of the “Critical Thinking for Successful Jobs-Think4Jobs” Partnership regarding the development of Critical Thinking Training Packages for Higher Education Instructors and Labour Market Organisations Tutors, namely Intellectual Output II. Considering previous research findings, it is suggested that despite HE and LMO instructors’ willingness to promote CT, they both might lack conceptual as well as procedural knowledge regarding CT. In order to assume that a common understanding between HE and LMOs can be achieved to promote CT skills development effectively in future graduates, the aim of this project was to develop a training course for HE instructors as well as LMO tutors. More specifically, the project aims to strengthen University-Business Collaboration for the effective promotion, development, support and assessment of students’ CT through their transition into a professional context using apprenticeships as a privileged interface in order to “bridge the gap” between their skills and those needed by the labour market. The specific objective of the second Intellectual Output was to develop a training curriculum for Higher Education Instructors and Labour Market Organisations Tutors on how to promote, develop, support and assess students’ CT in apprenticeships curricula as well as on how to develop blended curricula using Moodle. The training aimed at reaching 30 participants from the Partnership (i.e., 15 from Higher Education and 15 from Labour Market Organisations). To reach the aforementioned objective for the delivery of the Output, five activities were originally designed: 1. Define the goals, outcomes and assessment criteria of the training packages. 2. Identify the training subjects and design the activities to be held. 3. Identify, select and/or create training resources, which will support the activities during the training packages. 4. Develop a transnational training course. 5. Delivery of the training course. University of Western Macedonia (UOWM) was the leading Organisation for the delivery of the second Intellectual Output. A Participatory Co-Design (PC-D Methodology was implemented to map the participants’ requirements and needs for the training. For the implementation of the training course, participants from both the Higher Education and the Labor Market Organisations from the five countries partake as Trainers providing various workshops focusing on experiential learning. More specifically, workshops concerned the deconstruction and reconstruction of previously held ideas regarding CT, the development of a working definition on CT for the Think4Jobs project, instructional approaches and teaching strategies that promote CT, blended learning and Moodle, the assessment of CT as well as the preparation of the Memorandum of Understanding (MoU) between HE and LMOs. Finally, a reflective session on the work carried out for the MoU and a session for the design and development of the CT blended apprenticeship curricula were scheduled. According to the registrations, on a daily basis, 35 participants engaged in the LTTA. Participants' knowledge on conceptual and procedural knowledge regarding CT, evaluation of CT, as well as blended learning, University-Business Collaboration and Moodle were evaluated in a pre-post measurement. In order to assess participants’ previous knowledge as well as the knowledge acquired during the LTTA, two online questionnaires were used. The first questionnaire (pre-measurement) was administered to participants at the beginning of the training course, while the second questionnaire (post-measurement) at the end of the LTTA (122 items for the pre-test, 130 items for the post-test, including questions about participants’ commitment during LTTA and their evaluation of the LTTA). The data collection tool consisted of seven distinct parts. The first part concerned demographic information, while the second part assessed participants’ level of perceived self-confidence in the issues addressed in the LTTA, the Moodle’s ease of use and perceived self-efficacy. Parts three to five of the tool explored participants’ conceptions regarding myths and facts about conceptual and procedural knowledge of CT, the evaluation of CT, blended learning and the University and Business Collaboration. Moreover, participants’ level of confidence about their answers was also assessed. Statistical analysis of data collected suggested that participants’ knowledge about CT, blended learning and the University and Business Collaboration increased after their participation in the LTTA. However, these results were not statistically significant. A statistically significant median increase elicited only in participants’ perceived self-confidence on the topics addressed during the LTTA, only for HE participants. Finally, the administrative and management of the implemented LTTA was evaluated highlighting that the event reached the predefined objectives and goals, met participants’ expectations and offered a high quality learning and training experience to the participants. Apart from the measurable data, a significant outcome of the LTTA was the development of a Memorandum of Understanding (MoU) between each pair of HEIs and LMOs partner per country. The MoU set a specific framework on the expected collaboration between HE and LMOs for the design-development (IO3), implementation and evaluation (IO4) of the CT blended apprenticeships curricula. The development of MoUs suggest that a common understanding on the design and delivery of CT blended apprenticeships curricula has been achieved and that UBC has been tailored to each pair of contributors. Overall, the CT training course presented in the current report has contributed to the existing research and literature in numerous ways. First, it presented a course designed to address the specific needs of its participants, by employing a PC-D approach. Second, it presented a training course that can also be applied in the future, as an intensive program aiming to enhance CT in educational and LMO settings. Third, it actively engaged HE Instructors and LMOs in a common training course, trying to reach a common understanding. Finally, the current report contributes to the literature with the exploitation of a multiple-choice instrument incorporating a Certainty Response Index identifying not only participants’ alternative concepts but also their level of confidence on aspects of CT, blended learning and UBC

THINK4JOBS TOOLKIT Ten work-based learning scenarios

The current report is the first Intellectual Output (Output 1) of the THINK4JOBS initiative, which aims at improving students’ CT skills and dispositions by promoting collaboration between Higher Education Institutions (HEIs) and Labour Market Organizations (LMOs). This is the case since according to relevant research findings, LMOs seem to expect employees to acquire CT skills in order for them to successfully address the needs of their work positions. Under this rationale, partners of the two aforementioned fields have decided to redesign and ameliorate HEI curricula by blending both HEIs and LMOs’ experience, knowledge and recommendations, while instilling this evidence into students’ apprenticeships. Apprenticeships offering practice in professional skills can actively lead to students’ understanding of their working environment and simultaneously scaffold CT development with the employment of mentoring. For this reason, the THINK4JOBS initiative exploits apprenticeships as a means of CT exploration and learning through which bridging the gap between HEIs and LMOs can be attained. Therefore, it is considered that in this fashion, students will be acquainted with the concept of CT and also be in the position of transferring it into their work settings, when entering the workplace. It should be noted that partners of the THINK4JOBS project are representatives from five disciplines (teacher training, English as a foreign language – EFL, business economics, business informatics and veterinary medicine), who formed teams between HEI and LMOs for each of these disciplines in order for ideas to be pluralized and CT to be explored across a variety of domains. The current report has a twofold aim: · to trace and map the methods and/or techniques that CT is currently employed in HEIs and LMOs’ apprenticeships and apprenticeships focusing on any possible convergent or divergent points; · to thoroughly describe and suggest work-based, learning scenarios that could bridge the gap between HEIs and LMOs’ curricula and simultaneously attempt to safeguard the requirements for graduates’ CT development and improvement. Mapping the Gap Regarding the first aim of the report, three research methods (observation, focus groups and documentary analysis) were employed in combination with three instruments (observational matrix, focus group rubric and documentary analysis rubric). Each research instrument includes a set of variables, which are majorly organized in three categories: I. Pedagogical aspects of CT development (including class objectives, teaching strategies/methods, tools/materials and evaluation regarding CT) II. CT aspects (including the ways CT is nurtured, triggered and explicitly taught during instruction) III. Implementation of CT (including elements of CT presence in these disciplines) For each variable, a set of indicators, drawing on CT and pedagogical theory was also developed in order for the aforementioned research instruments to be constructed. Stakeholders (HEI students and instructors as well as LMO tutors, employers and employees) participated in the mapping process. Data were collected during the winter semester 2020-2021 and a total of 134 participants from all partner countries participated in the focus groups discussions. Regarding the other two research methods, observation was carried out in at least three apprenticeships or courses, with at least four observation sessions for each of them. As far as it concerns the documentary analysis, documents supporting the courses/apprenticeships, which were observed, were analyzed according to the relevant rubric. Findings from each research instrument were triangulated according to each discipline and are thoroughly described in the current report in separate sections. However, some general conclusions seem to derive from a holistic approach to data analysis. Initially, it was suggested that even though a definitive “gap” between HEIs and LMOs does not seem to exist, there is a different context in CT approach since universities usually employ different learning activities focusing more on career preparation with long-term goals while LMOs follow compact and short-term, learning and teaching strategies. Additionally, findings suggested that CT is a newly-added requirement for the workplace and that HEIs and LMOs do not opt for the same terminology when referring to the concept –meaning that HEIs usually select scientific terms. Another element, which is evident is that CT in HEIs is commonly expressed through a declarative manner, while in LMOs application to specific cases follows the procedural manner. Learning Scenarios Regarding the second aim of this report, each team of HEI and LMO constructed two learning scenarios according to the findings, the sets of recommendations and the already identified educational needs. From the ten work-based scenarios developed, one from every discipline was organized in a syllabus form so that it can be further utilized for the CT blended apprenticeship curricula. This information highlights the importance of the scenarios, since they will set the stage for introducing CT at programme and course levels by utilizing Intellectual Output 3 activities to design work-based curricula for each country and dynamically enhance collaboration between HEIs and LMOs. Under this rationale, this scenario includes descriptive information about the themes, concepts, aims and learning outcomes, the duration, the teaching approach, the learning environment and the evaluation regarding both domain specific and CT related elements. First Intellectual Output Impact The current report is of major importance for the continuation of the THINK4JOBS project since it sets the stage for a sequence of activities carried out during the Second and Third Intellectual Outputs aiming at the successful application of the blended apprenticeships curricula. Besides the report’s importance for the project continuation, it may also stand as a useful Toolkit for teachers, students and employers regarding the development of CT in the workplace. In general, according to research findings, HEIs and LMOs are differently goal-oriented regarding CT and the reason for this divergence lies in the very nature and general context of the two organizations. In other words, HEIs intend to prepare students for all jobs related to a domain, while LMOs aim at preparing an employee for a specific job in a specific organization. This conclusion seems to indicate a paradox: the two organizations work in parallel but they do not share common understanding. This is the reason why the First Intellectual Output may be an invaluable means in the exploration of CT through different perspectives; actively supporting HEI and LMO collaboration in the quest for common ground

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

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

Severity of neonatal influenza infection is driven by type I interferon and oxidative stress

Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are antiviral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza virus (IV) model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24 h post IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population