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1. Randomised multicentre effectiveness trial of rapid syndromic testing by panel assay in children presenting to European emergency departments with acute respiratory infections—trial protocol for the ADEQUATE Paediatric trial

Author

Alexander Ross, Andrew Atkinson, Maarten J Postma, Federica Vanoni, Julia A Bielicki, Fernando Antoñanzas, Herman Goossens, Elias Iosifidis, Emmanuel Roilides, Mark Lyttle, Elia Vitale, Malte Kohns Vasconcelos, Florence Allantaz, Claire Hawksworth, Pablo Rojo, Dalia Dawoud, Surbhi Malhotra-Kumar, Silke Peter, Hanna Renk, Marc Bonten, Manuel Gijon, Maggie Nyirenda Nyang’wa, Thea van Asselt, Anthony Hemeson, Cristina Prat Aymerich, Simon van der Pol, Parthena Savvidou, Sophie Vandepitte, Emma Gardiner, Michelle Clements, Yasmine Yau, Giulio Vecchia, Federica D’Ambrosio, Wietske Bouwman, Marjolein van Esschoten, Frank Leus, David de Pooter, Leen Timbermont, Juan Pablo Rodriguez Ruiz, Benjamin Hommel, Marie Tessonneau, Jean-Louis Tissier, Philippe Cleuziat, Pim van Dorst, Paula Rojas, Marino Gonzales, Harry Heijerman, Henri van Werkhoven, Maria Simitsopoulou, Kalliopi Pantzartzi, Kostas Zarras, Argyro Ftergioti, Maria Kitsou, Aristea Karypiadou, Charis Lampada, Konstantina Charisi, Olga Tsiatsiou, Elsa Chorafa, Elisavet Michailidou, Ann-Kathrin Stiegler, Carmen Junk, Kristina Kiesel, Maren Belschner, Maike Seyfried, Kristina Schmauder, Tobias Walter, Dominic Imort, Fabian Behret, Rahel Berger, Leon Pfeiffer, Emanuela Früh, Elena Robinson, Andrea Marten, Claudia Werner, Rosa Calderón, Fátima Machín, Laura Cabello, Andrea Seoane, Sofía Mesa, Lidia Oviedo, Luisa Barón, Irene Hernández, Lisa Capozzi, Louisa Brock, Cecilia Hultin, Louise F Hill, Alessia Severi Conti, and Gianluca Gualco

Subjects
Medicine
Abstract

Introduction Syndromic panel assays, that is, using one test to simultaneously target multiple pathogens with overlapping signs and symptoms, have been integrated into routine paediatric care over the past decade, mainly for more severely ill and hospitalised patients. Their wider availability and short turnaround times open the possibility to apply them to non-hospitalised patients as well. In this context, it is important to trial how clinicians make use of pathogen detection data and if their early availability influences management decisions, particularly antibiotic use and hospitalisation.Methods and analysis Advanced Diagnostics for Enhanced QUality of Antibiotic prescription in respiratory Tract infections in Emergency rooms is an individually randomised, controlled, open-label effectiveness trial comparing the impact of a respiratory pathogen panel assay (BIOFIRE Respiratory Panel 2.1plus) used as a rapid syndromic test on nasopharyngeal swabs in addition to the standard of care versus standard of care alone. The trial will 1:1 randomise 520 participants under the age of 18 at 7 paediatric emergency departments in 5 European countries. Inclusion criteria for the trial consist of two sets, with the first describing respiratory tract infections in paediatric patients and the second describing the situation of potential management uncertainty in which test results may immediately affect management decisions. Enrolment started in July 2021 and is expected to be completed in early 2024. We will perform a two-sample t-test assuming a pooled variance estimate to compare the log-transformed mean time on antibiotic treatment (in hours) and number of days alive out of the hospital within 14 days after study enrolment between the control and intervention arms.Ethics and dissemination The trial protocol and materials were approved by research ethics committees in all participating countries. The respiratory pathogen panel assay is CE marked (assessed to meet European regulations) and FDA (United States Food and Drug Administration) cleared for diagnostic use. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.Trial registration number NCT04781530.

Published
2024
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2. Profiling of humoral immune responses to norovirus in children across Europe

Author

Nele Villabruna, Ray W. Izquierdo-Lara, Claudia M. E. Schapendonk, Erwin de Bruin, Felicity Chandler, Tran Thi Nhu Thao, Brenda M. Westerhuis, Janko van Beek, Louise Sigfrid, Carlo Giaquinto, Herman Goossens, Julia A. Bielicki, Malte Kohns Vasconcelos, Pieter L. A. Fraaij, Marion P. G. Koopmans, and Miranda de Graaf

Subjects
Medicine, Science
Abstract

Abstract Norovirus is a leading cause of epidemic acute gastroenteritis. More than 30 genotypes circulate in humans, some are common, and others are only sporadically detected. Here, we investigated whether serology can be used to determine which genotypes infect children. We established a multiplex protein microarray with structural and non-structural norovirus antigens that allowed simultaneous antibody testing against 30 human GI and GII genotypes. Antibody responses of sera obtained from 287 children aged

Published
2022
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3. Migrating a Well-Established Longitudinal Cohort Database From Oracle SQL to Research Electronic Data Entry (REDCap): Data Management Research and Design Study

Author

Katharina Kusejko, Daniel Smith, Alexandra Scherrer, Paolo Paioni, Malte Kohns Vasconcelos, Karoline Aebi-Popp, Roger D Kouyos, Huldrych F Günthard, and Christian R Kahlert

Subjects
Medicine
Abstract

BackgroundProviding user-friendly electronic data collection tools for large multicenter studies is key for obtaining high-quality research data. Research Electronic Data Capture (REDCap) is a software solution developed for setting up research databases with integrated graphical user interfaces for electronic data entry. The Swiss Mother and Child HIV Cohort Study (MoCHiV) is a longitudinal cohort study with around 2 million data entries dating back to the early 1980s. Until 2022, data collection in MoCHiV was paper-based. ObjectiveThe objective of this study was to provide a user-friendly graphical interface for electronic data entry for physicians and study nurses reporting MoCHiV data. MethodsMoCHiV collects information on obstetric events among women living with HIV and children born to mothers living with HIV. Until 2022, MoCHiV data were stored in an Oracle SQL relational database. In this project, R and REDCap were used to develop an electronic data entry platform for MoCHiV with migration of already collected data. ResultsThe key steps for providing an electronic data entry option for MoCHiV were (1) design, (2) data cleaning and formatting, (3) migration and compliance, and (4) add-on features. In the first step, the database structure was defined in REDCap, including the specification of primary and foreign keys, definition of study variables, and the hierarchy of questions (termed “branching logic”). In the second step, data stored in Oracle were cleaned and formatted to adhere to the defined database structure. Systematic data checks ensured compliance to all branching logic and levels of categorical variables. REDCap-specific variables and numbering of repeated events for enabling a relational data structure in REDCap were generated using R. In the third step, data were imported to REDCap and then systematically compared to the original data. In the last step, add-on features, such as data access groups, redirections, and summary reports, were integrated to facilitate data entry in the multicenter MoCHiV study. ConclusionsBy combining different software tools—Oracle SQL, R, and REDCap—and building a systematic pipeline for data cleaning, formatting, and comparing, we were able to migrate a multicenter longitudinal cohort study from Oracle SQL to REDCap. REDCap offers a flexible way for developing customized study designs, even in the case of longitudinal studies with different study arms (ie, obstetric events, women, and mother-child pairs). However, REDCap does not offer built-in tools for preprocessing large data sets before data import. Additional software is needed (eg, R) for data formatting and cleaning to achieve the predefined REDCap data structure.

Published
2023
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4. Detection of mostly viral pathogens and high proportion of antibiotic treatment initiation in hospitalised children with community-acquired pneumonia in Switzerland – baseline findings from the first two years of the KIDS-STEP trial

Author

Malte Kohns Vasconcelos, Patrick M. Meyer Sauteur, Kristina Keitel, Regina Santoro, Adrian Egli, Michael Coslovsky, Michelle Seiler, Marco Lurà, Henrik Köhler, Natasha Loevy, Christian R. Kahlert, Ulrich Heininger, Johannes van den Anker, and Julia A. Bielicki

Subjects
Medicine
Abstract

AIMS OF THE STUDY: Globally, since the introduction of conjugate-vaccines against encapsulated bacteria, respiratory viruses have caused most hospitalisations for community-acquired pneumonia. The aim of this study was to describe pathogens detected and their association with clinical findings in Switzerland. METHODS: Baseline data were analysed for all trial participants enrolled between September 2018 and September 2020 into the KIDS-STEP Trial, a randomised controlled superiority trial on the effect of betamethasone on clinical stabilisation of children admitted with community-acquired pneumonia. Data included clinical presentation, antibiotic use and results of pathogen detection. In addition to routine sampling, nasopharyngeal specimens were analysed for respiratory pathogens using a panel polymerase chain reaction test covering 18 viral and 4 bacterial pathogens. RESULTS: 138 children with a median age of 3 years were enrolled at the eight trial sites. Fever (obligatory for enrolment) had been present for median 5 days before admission. Most common symptoms were reduced activity (129, 93.5%) and reduced oral intake (108, 78.3%). Oxygen saturation

Published
2023
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5. Paediatric refugees from Ukraine: guidance for health care providers

Author

Fabienne N. Jaeger, Christoph Berger, Michael Buettcher, Sarah Depallens, Ulrich Heininger, Yvon Heller, Malte Kohns Vasconcelos, Bodil Leforestier, Nicole Pellaud, Christa Relly, Johannes Trück, Saskia von Overbeck Ottino, Noémie Wagner, and Nicole Ritz

Subjects
Medicine
Abstract

BACKGROUND: With the invasion of Ukraine by the Russian Army in February 2022, refugees, the majority of whom are women and children, started fleeing the war to neighbouring countries. Even before the current escalation, the conflict in the eastern part of Ukraine has led to the internal displacement of more than 200,000 children, and many others have experienced attacks, e.g. on schools. This inevitably leads to limitations in health care delivery. During transit, overcrowding, poor shelter and vulnerability may further put refugees at increased risk for infectious diseases. This consensus document aims to provide information and guidance regarding health issues that paediatricians and general practitioners may face when caring for Ukrainian children. METHODS: Members of the Migrant Health Reference Group of Paediatrics Switzerland and the Paediatric Infectious Disease Group in Switzerland developed this recommendation between March and April 2022 in a modified Delphi process. RESULTS: A total of 50 recommendations were agreed on with a ≥80% consensus. These include the following topics: i) general aspects, including interpreter services, urgent health needs, personal history and general check-ups; ii) mental health, including how to search for signs of psychological distress without going into traumatic details; iii) vaccinations, including recommendations for evaluation and catch-up; iv) screening for tuberculosis, human immunodeficiency virus, and hepatitis B and C; and v) providing age-appropriate preventive and health service information. CONCLUSION: This document provides current evidence and guidance when caring for paediatric refugees from Ukraine. The recommendations focus on Switzerland but may well be used in other countries. These are based on current evidence and may need to be adapted to individual situations and once further evidence becomes available.

Published
2022
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6. Simultaneous presence of Mycoplasma salivarium and Tannerella forsythia in the implant sulcus after lateral augmentation with autogenous root grafts is associated with increased sulcus probing depth.

Author

Karoline Groß, Didem Sahin, Malte Kohns Vasconcelos, Klaus Pfeffer, Frank Schwarz, and Birgit Henrich

Subjects
Medicine, Science
Abstract

ObjectiveTo characterize a potential pathogenic role of Mycoplasma salivarium and bacterial co-detection patterns on different implant augmentation types.Material and methods36 patients were non-randomly assigned to autogenous lateral alveolar ridge augmentation with either cortical autogenous bone blocks, or healthy autogenous tooth roots or non-preservable teeth. Mucosal inflammation was assessed by probing pocket depth (PD) at all sampling sites and by bleeding on probing (BOP) in a subset of sampling sites, and standardized biofilm samples were obtained from the submucosal peri-implant sulcus and sulcus of a contralateral tooth at two times (t1 after implant placement; t2 after six months). Seven bacterial species were quantified using Taqman PCR.ResultsMucosal inflammation did not differ between augmentation groups, but peri-implant sulci showed increased abundance of M. salivarium after augmentation with autogenous tooth roots lasting for at least six months (t1 p = 0.05, t2 p = 0.011). In M. salivarium-positive samples, Tannerella forsythia was correlated with PD (R = 0.25, p = 0.035) This correlation was not observed in M. salivarium-negative samples. Compared to all other samples, PD was deeper in co-detection (i.e., simultaneous M. salivarium and T. forsythia) positive samples (p = 0.022). No association of single or co-detection of bacteria with BOP was observed.ConclusionPresence of M. salivarium in peri-implant sulci varies with augmentation method and is associated with increased PD but not BOP. A potential causal role of M. salivarium in inflammation through a mechanism involving co-presence of T. forsythia requires further study.

Published
2022
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7. Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe—results from the PED-MERMAIDS multicentre case–control study

Author

Cristina Calvo, Andrew Riordan, Liviana Da Dalt, Federico Martinón-Torres, Peter Horby, Julia A Bielicki, Maria Tsolia, Michael Sharland, Herman Goossens, Marion Koopmans, Despoina Gkentzi, Peter J Openshaw, Menno D de Jong, Elias Iosifidis, Emmanuel Roilides, Carlo Giaquinto, Louise Sigfrid, Margareta Ieven, Malte Kohns Vasconcelos, Pablo Rojo, Cristina Epalza, Sigita Burokiene, Hanna Renk, Samsul Islam, Vana Spoulou, Katherine Loens, Daniele Donà, Veerle Matheeussen, Savvas Papachristou, Manuel Gijon, Chiara Minotti, Jessica Jarvis, Aggeliki Syggelou, Maggie Nyirenda Nyang’wa, Sophie Keers, Anna-Lena Gemmel, Carmen D’Amore, Marta Ciofi degli Atti, Carmen Rodríguez-Tenreiro Sánchez, Tessa Goetghebuer, Markus Hufnagel, and Pieter L A Fraaij

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Background Both pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation.Methods 349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets.Results RSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses.Conclusion RSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent.

Published
2021
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8. Randomised placebo-controlled multicentre effectiveness trial of adjunct betamethasone therapy in hospitalised children with community-acquired pneumonia: a trial protocol for the KIDS-STEP trial

Author

Patrick M Meyer Sauteur, Julia Anna Bielicki, Malte Kohns Vasconcelos, Regina Santoro, Michael Coslovsky, Marco Lurà, Kristina Keitel, Tanja Wachinger, Svetlana Beglinger, Ulrich Heininger, and Johannes van den Anker

Subjects
Medicine
Abstract

Introduction Community-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids.Methods and analysis The KIDS-STEP trial is a multicentre, randomised, double-blind, placebo-controlled superiority trial of betamethasone treatment on outcome of hospitalised children with CAP. Children are enrolled in paediatric emergency departments of hospitals across Switzerland and randomised to adjunct oral betamethasone for 2 days or matching placebo in addition to standard of care treatment. The co-primary outcomes are the proportion of children clinically stable 48 hours after randomisation and the proportion of children with CAP-related readmission within 28 days after randomisation. Secondary outcomes include length of hospital stay, time away from routine childcare and healthcare utilisation and total antibiotic prescriptions within 28 days from randomisation.Each of the co-primary outcomes will be analysed separately. We will test clinical stability rates using a proportion test; to test non-inferiority in readmission rates, we will construct 1−α % CI of the estimated difference and test if it contains the pre-defined margin of 7%. Success is conditional on both tests. A simulation-based sample size estimation determined that recruiting 700 patients will ensure a power of 80% for the study.Ethics and dissemination The trial protocol and materials were approved by ethics committees in Switzerland (lead: Ethikkommission Nordwest und Zentralschweiz) and the regulatory authority Swissmedic. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.Trial registration number NCT03474991 and SNCTP000002864.

Published
2020
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9. Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Clusters Based on Integrated Genomic Surveillance, Outbreak Analysis and Contact Tracing in an Urban Setting

Author

Jessica Nicolai, Alona Tyshaieva, Marcel Andree, Klaus Pfeffer, Maximilian Damagnez, Lisanna Hülse, Lutz Ehlkes, Nadine Lübke, Patrick Finzer, Malte Kohns Vasconcelos, Klaus Göbels, Alexander Thielen, Teresa Tamayo, Rainer Zotz, Susanne Kolbe-Busch, Ashley Duplessis, Martin Däumer, Sandra Hauka, Tobias Wienemann, Jörg Timm, Katrin Hoffmann, Alexander T Dilthey, Daniel Strelow, Torsten Houwaart, and Andreas Walker

Subjects
Microbiology (medical), medicine.medical_specialty, Nanopore sequencing, Population, genomic epidemiology, rapid sequencing, Disease Outbreaks, infection chain, Environmental health, Major Article, medicine, Humans, Infection control, education, education.field_of_study, Molecular epidemiology, SARS-CoV-2, Transmission (medicine), business.industry, Public health, COVID-19, Outbreak, Genomics, community transmission, Identification (information), AcademicSubjects/MED00290, Infectious Diseases, Contact Tracing, business, Contact tracing
Abstract

Background Tracing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission chains is still a major challenge for public health authorities, when incidental contacts are not recalled or are not perceived as potential risk contacts. Viral sequencing can address key questions about SARS-CoV-2 evolution and may support reconstruction of viral transmission networks by integration of molecular epidemiology into classical contact tracing. Methods In collaboration with local public health authorities, we set up an integrated system of genomic surveillance in an urban setting, combining a) viral surveillance sequencing, b) genetically based identification of infection clusters in the population, c) integration of public health authority contact tracing data, and d) a user-friendly dashboard application as a central data analysis platform. Results Application of the integrated system from August to December 2020 enabled a characterization of viral population structure, analysis of 4 outbreaks at a maximum care hospital, and genetically based identification of 5 putative population infection clusters, all of which were confirmed by contact tracing. The system contributed to the development of improved hospital infection control and prevention measures and enabled the identification of previously unrecognized transmission chains, involving a martial arts gym and establishing a link between the hospital to the local population. Conclusions Integrated systems of genomic surveillance could contribute to the monitoring and, potentially, improved management of SARS-CoV-2 transmission in the population., Tracing of SARS-CoV-2 population transmission chains is still a major challenge. We present an integrated system of genomic surveillance and show it to be capable of detecting infection chains in a large city during ongoing community transmission.

Published
2021

10. Strikingly Decreased Community-acquired Pneumonia Admissions in Children Despite Open Schools and Day-care Facilities in Switzerland

Author

Ulrich Heininger, Regina Santoro, Patrick M. Meyer Sauteur, Malte Kohns Vasconcelos, Kristina Keitel, Julia Bielicki, John N. van den Anker, University of Zurich, and Kohns Vasconcelos, Malte

Subjects
Microbiology (medical), medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, 610 Medicine & health, 2725 Infectious Diseases, Day care, medicine.disease, Pediatrics, Perinatology, 2726 Microbiology (medical), and Child Health, Infectious Diseases, Community-acquired pneumonia, 10036 Medical Clinic, Pediatrics, Perinatology and Child Health, Emergency medicine, medicine, 2735 Pediatrics, Perinatology and Child Health, business
Published
2021

11. Randomised placebo-controlled multicentre effectiveness trial of adjunct betamethasone therapy in hospitalised children with community-acquired pneumonia: a trial protocol for the KIDS-STEP trial

Author

Tanja Wachinger, Julia Bielicki, Ulrich Heininger, Svetlana Beglinger, Johannes N. van den Anker, Patrick M. Meyer Sauteur, Marco Lurà, Michael Coslovsky, Malte Kohns Vasconcelos, Kristina Keitel, Regina Santoro, University of Zurich, and Kohns Vasconcelos, Malte

Subjects
Adult, medicine.medical_specialty, 610 Medicine & health, 2700 General Medicine, paediatric infectious disease & immunisation, Placebo, Betamethasone, Superiority Trial, Community-acquired pneumonia, Informed consent, Health care, medicine, accident & emergency medicine, Humans, Multicenter Studies as Topic, Medical prescription, Child, Randomized Controlled Trials as Topic, business.industry, SARS-CoV-2, COVID-19, Paediatrics, General Medicine, Pneumonia, medicine.disease, Treatment Outcome, 10036 Medical Clinic, Emergency medicine, paediatric thoracic medicine, Medicine, Observational study, business, paediatric A&E and ambulatory care, Child, Hospitalized, Switzerland, medicine.drug
Abstract

IntroductionCommunity-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids.Methods and analysisThe KIDS-STEP trial is a multicentre, randomised, double-blind, placebo-controlled superiority trial of betamethasone treatment on outcome of hospitalised children with CAP. Children are enrolled in paediatric emergency departments of hospitals across Switzerland and randomised to adjunct oral betamethasone for 2 days or matching placebo in addition to standard of care treatment. The co-primary outcomes are the proportion of children clinically stable 48 hours after randomisation and the proportion of children with CAP-related readmission within 28 days after randomisation. Secondary outcomes include length of hospital stay, time away from routine childcare and healthcare utilisation and total antibiotic prescriptions within 28 days from randomisation.Each of the co-primary outcomes will be analysed separately. We will test clinical stability rates using a proportion test; to test non-inferiority in readmission rates, we will construct 1−α % CI of the estimated difference and test if it contains the pre-defined margin of 7%. Success is conditional on both tests. A simulation-based sample size estimation determined that recruiting 700 patients will ensure a power of 80% for the study.Ethics and disseminationThe trial protocol and materials were approved by ethics committees in Switzerland (lead: Ethikkommission Nordwest und Zentralschweiz) and the regulatory authority Swissmedic. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate.Trial registration numberNCT03474991 and SNCTP000002864.

Published
2020

12. Effect of amoxicillin dose and treatment duration on the need for antibiotic re-treatment in children with community-acquired pneumonia: The CAP-IT randomized clinical trial

Author

Bielicki, Julia A., Stöhr, Wolfgang, Barratt, Sam, Dunn, David, Naufal, Nishdha, Roland, Damian, Sturgeon, Kate, Finn, Adam, Rodriguez Ruiz, Juan Pablo, Malhotra, Surbhi, Powell, Colin, Faust, Saul N., Alcock, Anastasia E., Hall, Dani, Robinson, Gisela, Hawcutt, Daniel B., Lyttle, Mark D., Gibb, Diana M., Sharland, Mike, Molyneux, Elizabeth, Butler, Chris C., Smyth, Alan, Prichard, Catherine, Peto, Tim E.A., Cousens, Simon, Logan, Stuart, Bamford, Alasdair, Turkova, Anna, Goodman, Anna L., Fitzgerald, Felicity, Little, Paul S., Robotham, Julie, Wan, Mandy, Klein, Nigel, Rogers, Louise, Vitale, Elia, Rotheram, Matthew, Wright, Rachel, Lee, Elizabeth, Ohia, Udeme, Hartshorn, Stuart, Jyothish, Deepthi, Hopkins, Juliet, Ross, James G., Patel, Poonam, Fletcher, Hannah, Nundlall, Kribashnie, Carungcong, Jamie, Bull, Rhian, Burney, Nabila, Correia Da Costa, Patricia, Vergnano, Stefania, Walton, Beth, Smith, Alice, Ross, Michelle, Aplin, Lucie, Sheedy, Sarah, Kaur, Gurnie, Morgan, Jeff, Muller, Jennifer, Marshall, Gail, Nyamugunduru, Godfrey, Furness, John C., Eggington, Dawn, Holt, Susannah J., Gibbs, John, Burchett, Caroline, Lonsdale, Caroline, De-Beger, Sarah, Cheung, Ronny, Sheedy, Alyce B., Ahmad, Mohammad, Stockwell, Zoe, Giwa, Sarah, Murad, Arshid, Jerman, Katherine, Green, Joanna, Bird, Chris, Baron, Tanya K. Z., Segal, Shelley, Beer, Sally, Garcia Garcia, Maria Jose, Georgiou, Dom, Beadon, Kirsten, Martinez, Jose, Cantle, Fleur, Eastman, Hannah, Riozzi, Paul, Cotton, Hannah, Mullen, Niall, McCrone, Rhona, Corrigan, Paul, Salt, Gemma, Fairlie, Louise, Smith, Andrew, Starkey, Lizzie, Hayman, Mel, O'Riordan, Sean, Downes, Alice, Allen, Majorie, Turner, Louise, Ellis, Donna, Bandi, Srini, Patel, Rekha, Gough, Chris, McAulay, Megan, Conner, Louise, Gardner, Sharryn, Haslam, Zena, Morrison, Moira, Barrett, Michael J., Niermeyer, Madeleine, Barry, Ellen, Walton, Emily K., Kapur, Akshat, Richmond, Vivien, Foster, Steven J., Bland, R.M., Neil, Ashleigh, Milligan, Barry, Bannister, Helen, Bloom, Ben, Parikh, Ami, Skene, Imogen, Power, Helen, Boulton, Olivia, Astin-Chamberlain, Raine, Smith, David, Walters, Jonathon, Martin, Daniel, Noba, Lyrics, Potier, Katherine, Borland, Fiona, Wilson, Jill, Suleman, Zainab, Gilchrist, Judith, West, Noreen, Evans, Jayne, Morecombe, Juliet, Heath, Paul T., Iqbal, Yasser, Kohns Vasconcelos, Malte, Stefanova, Elena, Womack, Claire, Maconochie, Ian K., Laing, Suzanne, Jorgensen, Rikke, Nyirenda, Maggie, Keers, Sophie, Pilgrim, Samia, Gardiner, Emma, Cathie, Katrina, Bayreuther, Jane, Ensom, Ruth, Cornish, Emily K., Herrieven, Elizabeth-Jayne L., Townend, William, Sherris, Leanne, and Williams, Paul

Subjects
Male, medicine.medical_specialty, Randomization, Administration, Oral, Severity of Illness Index, Drug Administration Schedule, law.invention, Community-acquired pneumonia, Randomized controlled trial, law, Internal medicine, Severity of illness, medicine, Clinical endpoint, Humans, Duration of Therapy, business.industry, Pharmacology. Therapy, Hazard ratio, Respiratory infection, Amoxicillin, Infant, General Medicine, Pneumonia, medicine.disease, Patient Discharge, Anti-Bacterial Agents, Community-Acquired Infections, Child, Preschool, Retreatment, Female, Human medicine, business, medicine.drug
Abstract

This randomized clinical trial compares the need for re-treatment of respiratory infection following hospitalization for community-acquired pneumonia among children receiving amoxicillin at high doses vs low doses and at 3-days vs 7-days duration. Question For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day noninferior to 70 to 90 mg/kg per day, and is a 3-day course noninferior to 7 days, with regard to the need for antibiotic re-treatment? Findings In this 2 x 2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic re-treatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin. Meaning Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day was noninferior to a dose of 70 to 90 mg/kg per day and 3 days was noninferior to 7 days with regard to the need for later antibiotic re-treatment. Importance The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants Multicenter, randomized, 2 x 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -infinity to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -infinity to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -infinity to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -infinity to 7.4%]; P value for interaction = .73). Conclusions and Relevance Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Published
2021

13. Aetiology of acute respiratory infection in preschool children requiring hospitalisation in Europe-results from the PED-MERMAIDS multicentre case-control study

Author

Menno D. de Jong, Markus Hufnagel, Katherine Loens, Cristina Epalza, Peter J. M. Openshaw, Vana Spoulou, Federico Martinón-Torres, Emmanuel Roilides, Maggie Nyirenda Nyang'wa, Elias Iosifidis, Mike Sharland, Hanna Renk, Cristina Calvo, Marta Ciofi Degli Atti, Carlo Giaquinto, Marion Koopmans, Manuel Gijon, Sigita Burokienė, Veerle Matheeussen, Pablo Rojo, Chiara Minotti, Tessa Goetghebuer, Carmen D'Amore, Savvas Papachristou, Herman Goossens, Liviana Da Dalt, Malte Kohns Vasconcelos, Julia Bielicki, Sophie Keers, Samsul Islam, Maria Tsolia, Jessica Jarvis, Carmen Rodriguez-Tenreiro Sánchez, Despoina Gkentzi, Louise Sigfrid, Peter Horby, Pieter L. A. Fraaij, Anna-Lena Gemmel, Andrew Riordan, Daniele Donà, Aggeliki Syggelou, Margareta Ieven, Virology, Pediatrics, National Institute for Health Research, Asthma UK, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, viruses, Population, Respiratory Epidemiology, Respiratory Syncytial Virus Infections, medicine.disease_cause, Virus, 03 medical and health sciences, Diseases of the respiratory system, 0302 clinical medicine, respiratory infection, 030225 pediatrics, Internal medicine, Streptococcus pneumoniae, medicine, Humans, media_common.cataloged_instance, pneumonia, 030212 general & internal medicine, European union, education, Respiratory Tract Infections, media_common, clinical epidemiology, paediatric lung disaese, viral infection, education.field_of_study, RC705-779, business.industry, Respiratory infection, medicine.disease, 3. Good health, respiratory tract diseases, Hospitalization, Pneumonia, Case-Control Studies, Child, Preschool, Respiratory Syncytial Virus, Human, Attributable risk, Etiology, Medicine, Human medicine, business
Abstract

BackgroundBoth pathogenic bacteria and viruses are frequently detected in the nasopharynx (NP) of children in the absence of acute respiratory infection (ARI) symptoms. The aim of this study was to estimate the aetiological fractions for ARI hospitalisation in children for respiratory syncytial virus (RSV) and influenza virus and to determine whether detection of specific respiratory pathogens on NP samples was associated with ARI hospitalisation.Methods349 children up to 5 years of age hospitalised for ARI (following a symptom-based case definition) and 306 hospital controls were prospectively enrolled in 16 centres across seven European Union countries between 2016 and 2019. Admission day NP swabs were analysed by multiplex PCR for 25 targets.ResultsRSV was the leading single cause of ARI hospitalisations, with an overall population attributable fraction (PAF) of 33.4% and high seasonality as well as preponderance in younger children. Detection of RSV on NP swabs was strongly associated with ARI hospitalisation (OR adjusted for age and season: 20.6, 95% CI: 9.4 to 45.3). Detection of three other viral pathogens showed strong associations with ARI hospitalisation: influenza viruses had an adjusted OR of 6.1 (95% CI: 2.5 to 14.9), parainfluenza viruses (PIVs) an adjusted OR of 4.6 (95% CI: 1.8 to 11.3) and metapneumoviruses an adjusted OR of 4.5 (95% CI: 1.3 to 16.1). Influenza viruses had a PAF of 7.9%, PIVs of 6.5% and metapneumoviruses of 3.0%. In contrast, most other pathogens were found in similar proportions in cases and controls, including Streptococcus pneumoniae, which was weakly associated with case status, and endemic coronaviruses.ConclusionRSV is the predominant cause of ARI hospitalisations in young children in Europe and its detection, as well as detection of influenza virus, PIV or metapneumovirus, on NP swabs can establish aetiology with high probability. PAFs for RSV and influenza virus are highly seasonal and age dependent.

Published
2021

14. Medical history and clinical examinations are insufficient to exclude vertical human immunodeficiency virus transmission in healthy, at‐risk adolescents

Author

Jennifer Neubert, Malte Kohns Vasconcelos, Hans-Jürgen Laws, and Arndt Borkhardt

Subjects
Pediatrics, medicine.medical_specialty, Adolescent, medicine.diagnostic_test, business.industry, Infectious disease transmission, Medical record, MEDLINE, HIV Infections, Physical examination, Human immunodeficiency virus transmission, General Medicine, Infectious Disease Transmission, Vertical, Medical Records, Risk Factors, Pediatrics, Perinatology and Child Health, Humans, Medicine, Medical history, business, Physical Examination
Published
2019

15. Paediatric primary care in Germany during the early COVID-19 pandemic: the calm before the storm

Author

Hans Martin Bosse, Daniela Vesterling-Hörner, Hanna Renk, Mehrsad Klemm, Katharina Weil, Katharina Remke, Tarik el Scheich, and Malte Kohns Vasconcelos

Subjects
Medicine (General), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Adolescent, Population, Primary care, child Health, community-acquired infections, 03 medical and health sciences, R5-920, 0302 clinical medicine, Germany, Surveys and Questionnaires, Health care, Pandemic, medicine, Humans, 030212 general & internal medicine, Pediatricians, education, Child, Quality of Health Care, Original Research, Response rate (survey), education.field_of_study, High prevalence, Primary Health Care, business.industry, Public health insurance, SARS-CoV-2, Public Health, Environmental and Occupational Health, Infant, Newborn, COVID-19, Infant, Family medicine, Child, Preschool, Chronic Disease, Family Practice, business, 030217 neurology & neurosurgery
Abstract

ObjectivesGlobally, the COVID-19 pandemic has a major impact on healthcare provision. The effects in primary care are understudied. This study aimed to explore changes in consultation numbers and patient management during the COVID-19 pandemic, and to identify challenges for patient care.DesignSurvey of paediatric primary care practices on consultation numbers and patient management changes, and semistructured interviews to identify challenges for patient care. Surveys and interviews were partially linked in an explanatory sequential design to identify patient groups perceived to be at higher risk for worse care during the pandemic.SettingIn and around Düsseldorf, a densely populated area in Western Germany. The primary care facilities are spread over an area with approximately 2 million inhabitants.ParticipantsPrimary care in Germany is provided through practices run by self-employed specialist physicians that are contracted to offer services to patients under public health insurance which is compulsory to the majority of the population. The sample contained 44 paediatric primary care practices in the area, the response rate was 50%.ResultsNumbers of consultations for scheduled developmental examinations remained unchanged compared with the previous year while emergency visits were strongly reduced (mean 87.3 less/week in March–May 2020 compared with 2019, median reduction 55.0%). Children dependent on developmental therapy and with chronic health conditions were identified as patient groups receiving deteriorated care. High patient numbers, including of mildly symptomatic children presenting for health certificates, in combination with increased organisational demands and expected staff outages are priority concerns for the winter.ConclusionsPrimary care paediatricians offered stable service through the early pandemic but expected strained resources for the upcoming winter. Unambiguous guidance on which children should present to primary care and who should be tested would help to allocate resources appropriately, and this guidance needs to consider age group specific issues including high prevalence of respiratory symptoms, dependency on carers and high contact rates.

Published
2021

16. Primary care during the COVID-19 pandemic – observations and challenges identified through a survey and interviews with community paediatricians: the calm before the storm

Author

Daniela Vesterling-Hörner, Mehrsad Klemm, Katharina Weil, Katharina Remke, Hans Martin Bosse, Malte Kohns Vasconcelos, Hanna Renk, and Tarik el Scheich

Subjects
Response rate (survey), medicine.medical_specialty, Developmental therapy, High prevalence, Coronavirus disease 2019 (COVID-19), business.industry, Family medicine, Health care, Pandemic, medicine, Primary care, business, Patient management
Abstract

BackgroundGlobally, the COVID-19 pandemic has a major impact on healthcare provision. The effects in primary care are understudied.AimTo document changes in consultation numbers and patient management during the COVID-19 pandemic, and to identify challenges for patient care.MethodsSurvey of 44 paediatric primary care practices on consultation numbers and patient management changes (response rate 50%), and semi-structured interviews to identify challenges for patient care.ResultsNumbers of consultations for scheduled developmental examinations remained unchanged compared to the previous year while emergency visits were strongly reduced (mean 87.3 less/week in March–May 2020 compared to 2019, median reduction 55.0%). Children dependent on developmental therapy and with chronic health conditions were identified as patient groups receiving deteriorated care. High patient numbers, including of mildly symptomatic children presenting for health certificates, in combination with increased organisational demands and expected staff outages are priority concerns for the winter.ConclusionPrimary care paediatricians offered stable service through the early pandemic but expect strained resources for the upcoming winter. Unambiguous guidance on which children should present to primary care and who should be tested would help to allocate resources appropriately, and this guidance needs to consider age group specific issues including high prevalence of respiratory symptoms, dependency on carers and high contact rates.

Published
2021

17. COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Author

Abdukahil, Sheryl, Hssain, Ali, Tamlihat, Younes, Alidjnou, Kazali, de Brito, Carlos, Assie, Jean, Rincon, Diego, Humaid, Felwa, Bosse, Hans, Calvache, Jose, Carrier, François, Cavalli, Giulio, Cheng, Matthew, Cho, Hwa, Cho, Sung, Cidade, Jose, Herreros, Jose, Citarella, Barbara, Colombo, Sebastiano, Corpuz, Arianne, D’orleans, Charles, de Oliveira França, Rafael, Dewayanti, Santi, Diaz, Juan, Douglas, James, Mangoni, Emanuele, Dyrhol-Riise, Anne, Vidal, José, Sanharawi, Mohammed, Everding, Anna, Fatoni, Arie, Devouge, Eglantine, Florio, Letizia, Fonseca, Claudio, Freire, Marcela, Ribeiro, Ana, Curto, Elena, Morlaes, Louis, Grandin, Edward, Grieco, Domenico, Lordemann, Anja, Ho, Antonia, Holter, Jan, Horcajada, Juan, Dominguez, Carmen, Sotomayor, Ruth, García, Ruth, Kandamby, Darshana, Johal, Simreen, Kildal, Anders, Bekken, Gry, Vasconcelos, Malte, Vecham, Pavan, Lantang, Eka, Santos, Marta, Lee, Su, Bassi, Gianluigi, Lim, Wei, Lucet, Jean, Müller, Karl, Sanchez, Juan, Maier, Lars, Sant, Ceila, Eid, Charbel, Martelli, Celina, Rego, Caroline, Marwali, Eva, Jimenez, Juan, Maldonado, Hugo, Tutillo, Diego, Perrot, Clara, Myrodia, Dimitra, Ng, Pauline, Ng, Wing, Choileain, Orna, Oinam, Budha, Oliveira, Ana, Orozco-Chamorro, Claudia, Panda, Prasan, Reyes, Luis, Rios, Ana, Nuñez, Maria, Abreu, Julia, Holten, Aleksander, Choez, Xavier, Shum, Hoi, Mohammed, Nassima, Silva, Maria, Sin, Wai, Song, Myung, Uva, Maria, Svistunov, Magdalena, Thuy, Duong, Vijayaraghavan, Bharath, Santos-Olmo, Rosario, Trieu, Huynh, Villanueva, Joy, Abdukahil, Sheryl Ann, Abe, Ryuzo, Abel, Laurent, Absil, Lara, Acker, Andrew, Adachi, Shingo, Adam, Elisabeth, Adrião, Diana, Ainscough, Kate, Hssain, Ali Ait, Tamlihat, Younes Ait, Akimoto, Takako, Al-Dabbous, Tala, Al-Fares, Abdulrahman, Al Qasim, Eman, Alalqam, Razi, Alex, Beatrice, Alexandre, Kévin, Alfoudri, Huda, Alidjnou, Kazali Enagnon, Aliudin, Jeffrey, Allavena, Clotilde, Allou, Nathalie, Alves, João, Alves, Rita, Amaral, Maria, Ammerlaan, Heidi, Ampaw, Phoebe, Andini, Roberto, Andrejak, Claire, Angheben, Andrea, Angoulvant, François, Ansart, Séverine, Antonelli, Massimo, de Brito, Carlos Alexandre Antunes, Arabi, Yaseen, Aragao, Irene, Arcadipane, Antonio, Arenz, Lukas, Arlet, Jean-Benoît, Arnold-Day, Christel, Arora, Lovkesh, Artaud-Macari, Elise, Asensio, Angel, Assie, Jean Baptiste, Atique, Anika, Auchabie, Johann, Aumaitre, Hugues, Azemar, Laurène, Azoulay, Cécile, Bach, Benjamin, Bachelet, Delphine, Baillie, J. Kenneth, Bak, Erica, Bakakos, Agamemnon, Banisadr, Firouzé, Barbalho, Renata, Barclay, Wendy, Barnikel, Michaela, Barrelet, Audrey, Barrigoto, Cleide, Basmaci, Romain, Rincon, Diego Fernando Bautista, Bedossa, Alexandra, Behilill, Sylvie, Beljantsev, Aleksandr, Bellemare, David, Beltrame, Anna, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bennett, Suzanne, Bento, Luís, Berdal, Jan-Erik, Bergeaud, Delphine, Bertolino, Lorenzo, Bessis, Simon, Bevilcaqua, Sybille, Bhavsar, Krishna, Humaid, Felwa Bin, Bissuel, François, Biston, Patrick, Bitker, Laurent, Blanco-Schweizer, Pablo, Blot, Mathieu, Boccia, Filomena, Bogaert, Debby, Bompart, François, Booth, Gareth, Borges, Diogo, Borie, Raphaël, Bos, Jeannet, Bosse, Hans Martin, Botelho-Nevers, Elisabeth, Bouadma, Lila, Bouchaud, Olivier, Bouchez, Sabelline, Bouhmani, Dounia, Bouhour, Damien, Bouiller, Kévin, Bouillet, Laurence, Bouisse, Camille, Boureau, Anne-Sophie, Bouscambert, Maude, Bouziotis, Jason, Boxma, Bianca, Boyer-Besseyre, Marielle, Boylan, Maria, Braga, Cynthia, Brandenburger, Timo, Brazzi, Luca, Breen, Dorothy, Breen, Patrick, Brickell, Kathy, Brozzi, Nicolas, Buchtele, Nina, Buesaquillo, Christian, Bugaeva, Polina, Buisson, Marielle, Burhan, Erlina, Bustos, Ingrid, Butnaru, Denis, Cárcel, Sheila, Cabie, André, Cabral, Susana, Caceres, Eder, Callahan, Mia, Calligy, Kate, Calvache, Jose Andres, Camões, João, Campana, Valentine, Campbell, Paul, Canepa, Cecilia, Cantero, Mireia, Caraux-Paz, Pauline, Cardoso, Filipa, Cardoso, Filipe, Cardoso, Sofia, Carelli, Simone, Carlier, Nicolas, Carney, Gayle, Carpenter, Chloe, Carret, Marie-Christine, Carrier, François Martin, Carson, Gail, Casanova, Maire-Laure, Cascão, Mariana, Casimiro, José, Cassandra, Bailey, Castañeda, Silvia, Castanheira, Nidyanara, Castor-Alexandre, Guylaine, Castrillón, Henry, Castro, Ivo, Catarino, Ana, Catherine, François-Xavier, Cavalin, Roberta, Cavalli, Giulio Giovanni, Cavayas, Alexandros, Ceccato, Adrian, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chakveatze, Catherine, Chan, Adrienne, Chand, Meera, Chas, Julie, Chassin, Camille, Chen, Anjellica, Chen, Yih-Sharng, Cheng, Matthew Pellan, Cheret, Antoine, Chiarabini, Thibault, Chica, Julian, Chirouze, Catherine, Chiumello, Davide, Cho, Hwa Jin, Cho, Sung Min, Cholley, Bernard, Cidade, Jose Pedro, Herreros, Jose Miguel Cisneros, Citarella, Barbara Wanjiru, Ciullo, Anna, Clarke, Jennifer, Clohisey, Sara, Codan, Cassidy, Cody, Caitriona, Coelho, Alexandra, Colin, Gwenhaël, Collins, Michael, Colombo, Sebastiano Maria, Combs, Pamela, Connelly, J., Connor, Marie, Conrad, Anne, Contreras, Sofía, Cooke, Graham, Copland, Mary, Cordel, Hugues, Corley, Amanda, Cormican, Sarah, Cornelis, Sabine, Corpuz, Arianne Joy, Corvaisier, Grégory, Couffignal, Camille, Couffin-Cadiergues, Sandrine, Courtois, Roxane, D’orleans, Charles Crepy, Croonen, Sabine, Crowl, Gloria, Crump, Jonathan, Cruz, Claudina, Csete, Marc, Cucino, Alberto, Cullen, Caroline, Cummings, Matthew, Curley, Gerard, Curlier, Elodie, Custodio, Paula, D’aragon, Frédérick, da Silva Filipe, Ana, da Silveira, Charlene, D’ortenzio, Eric, Dabaliz, Al-Awwab, Dagens, Andrew, Dalton, Heidi, Dalton, Jo, Daneman, Nick, Dankwa, Emmanuelle, Dantas, Jorge, de Castro, Nathalie, de Mendoza, Diego, de Oliveira França, Rafael Freitas, de Rosa, Rosanna, de Silva, Thushan, de Vries, Peter, Dean, David, Debray, Marie-Pierre, Dechert, William, Deconninck, Lauren, Decours, Romain, Delacroix, Isabelle, Delavigne, Karen, Deligiannis, Ionna, Dell’amore, Andrea, Delobel, Pierre, Demonchy, Elisa, Denis, Emmanuelle, Deplanque, Dominique, Depuydt, Pieter, Desai, Mehul, Descamps, Diane, Desvallée, Mathilde, Dewayanti, Santi Rahayu, Diallo, Alpha, Diamantis, Sylvain, Dias, André, Diaz, Juan Jose Diaz, Diaz, Rodrigo, Didier, Kévin, Diehl, Jean-Luc, Dieperink, Wim, Dimet, Jérôme, Dinot, Vincent, Diouf, Alphonsine, Dishon, Yael, Djossou, Félix, Docherty, Annemarie, Dong, Andy, Donnelly, Christl, Donnelly, Maria, Donohue, Chloe, Dorival, Céline, Douglas, James Joshua, Douma, Renee, Dournon, Nathalie, Downer, Triona, Downing, Mark, Drake, Tom, Dubee, Vincent, Dubos, François, Ducancelle, Alexandra, Dudman, Susanne, Dunning, Jake, Mangoni, Emanuele Durante, Duranti, Silvia, Durham, Lucian, Dussol, Bertrand, Duval, Xavier, Dyrhol-Riise, Anne Margarita, Eira, Carla, Vidal, José Ernesto, Sanharawi, Mohammed El, Elapavaluru, Subbarao, Elharrar, Brigitte, Elkheir, Natalie, Ellerbroek, Jacobien, Ellis, Rachael, Eloy, Philippine, Elshazly, Tarek, Enderle, Isabelle, Engelmann, Ilka, Enouf, Vincent, Epaulard, Olivier, Esperatti, Mariano, Esperou, Hélène, Esposito-Farese, Marina, Estevão, João, Etienne, Manuel, Ettalhaoui, Nadia, Everding, Anna Greti, Evers, Mirjam, Fabre, Isabelle, Faheem, Amna, Fahy, Arabella, Fairfield, Cameron, Faria, Pedro, Farshait, Nataly, Fatoni, Arie Zainul, Faure, Karine, Fayed, Mohamed, Feely, Niamh, Fernandes, Jorge, Fernandes, Marília, Fernandes, Susana, Ferrão, Joana, Devouge, Eglantine Ferrand, Ferraz, Mário, Ferreira, Benigno, Ferrer-Roca, Ricard, Figueiredo-Mello, Claudia, Flateau, Clara, Fletcher, Tom, Florio, Letizia Lucia, Foley, Claire, Fomin, Victor, Fonseca, Claudio Duarte, Fonseca, Tatiana, Fontela, Patricia, Forsyth, Simon, Foti, Giuseppe, Fourn, Erwan, Fowler, Rob, Franch-Llasat, Diego, Fraser, Christophe, Fraser, John, Freire, Marcela Vieira, Ribeiro, Ana Freitas, Friedrich, Caren, Fry, Stéphane, Fuentes, Nora, Fukuda, Masahiro, Gómez-Junyent, Joan, Gaborieau, Valérie, Gachet, Benoît, Gaci, Rostane, Gagliardi, Massimo, Gagnard, Jean-Charles, Gagneux-Brunon, Amandine, Gaião, Sérgio, Gallagher, Phil, Curto, Elena Gallego, Gamble, Carrol, Garan, Arthur, Garcia-Gallo, Esteban, Garcia, Rebekha, Garot, Denis, Garrait, Valérie, Gault, Nathalie, Gavin, Aisling, Gaymard, Alexandre, Gebauer, Johannes, Morlaes, Louis Gerbaud, Germano, Nuno, Ghosn, Jade, Giani, Marco, Giaquinto, Carlo, Gibson, Jess, Gigante, Tristan, Gilg, Morgane, Giordano, Guillermo, Girvan, Michelle, Gissot, Valérie, Giwangkancana, Gezy, Glikman, Daniel, Glybochko, Petr, Gnall, Eric, Goco, Geraldine, Goehringer, François, Goepel, Siri, Goffard, Jean-Christophe, Golob, Jonathan, Gorenne, Isabelle, Goujard, Cécile, Goulenok, Tiphaine, Grable, Margarite, Grandin, Edward Wilson, Granier, Pascal, Grasselli, Giacomo, Green, Christopher, Greenhalf, William, Greffe, Segolène, Grieco, Domenico Luca, Griffee, Matthew, Griffiths, Fiona, Grigoras, Ioana, Groenendijk, Albert, Lordemann, Anja Grosse, Gruner, Heidi, Gu, Yusing, Guedj, Jérémie, Guellec, Dewi, Guerguerian, Anne-Marie, Guerreiro, Daniela, Guery, Romain, Guillaumot, Anne, Guilleminault, Laurent, Guimard, Thomas, Haber, Daniel, Hakak, Sheeba, Hall, Matthew, Halpin, Sophie, Hamer, Ansley, Hamidfar, Rebecca, Hammond, Terese, Hardwick, Hayley, Harley, Kristen, Harrison, Ewen, Harrison, Janet, Hays, Leanne, Heerman, Jan, Heggelund, Lars, Hendry, Ross, Hennessy, Martina, Henriquez-Trujillo, Aquiles, Hentzien, Maxime, Hernandez-Montfort, Jaime, Hidayah, Astarini, Higgins, Dawn, Higgins, Eibhilin, Hinton, Samuel, Hipólito-Reis, Ana, Hiraiwa, Hiroaki, Hiscox, Julian, Ho, Antonia Ying Wai, Hoctin, Alexandre, Hoffmann, Isabelle, Hoiting, Oscar, Holt, Rebecca, Holter, Jan Cato, Horby, Peter, Horcajada, Juan Pablo, Hoshino, Koji, Hoshino, Kota, Hough, Catherine, Hsu, Jimmy Ming-Yang, Hulot, Jean-Sébastien, Ijaz, Samreen, Illes, Hajnal-Gabriela, Inácio, Hugo, Dominguez, Carmen Infante, Iosifidis, Elias, Irvine, Lacey, Isgett, Sarah, Isidoro, Tiago, Isnard, Margaux, Itai, Junji, Ivulich, Daniel, Jaafoura, Salma, Jabot, Julien, Jackson, Clare, Jamieson, Nina, Jaureguiberry, Stéphane, Javidfar, Jeffrey, Jean-Benoît, Zabbe, Jego, Florence, Jenum, Synne, Sotomayor, Ruth Jimbo, García, Ruth Noemí Jorge, Joseph, Cédric, Joseph, Mark, Jouvet, Philippe, Jung, Hanna, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabina, Kalomoiri, Smaragdi, Kandamby, Darshana Hewa, Kandel, Chris, Kant, Ravi, Kartsonaki, Christiana, Kasugai, Daisuke, Katz, Kevin, Johal, Simreen Kaur, Keating, Sean, Kelly, Andrea, Kelly, Sadie, Kennedy, Lisa, Kennon, Kalynn, Kerroumi, Younes, Kestelyn, Evelyne, Khalid, Imrana, Khalil, Antoine, Khan, Coralie, Khan, Irfan, Kho, Michelle, Khoo, Saye, Kida, Yuri, Kiiza, Peter, Kildal, Anders Benjamin, Kimmoun, Antoine, Kindgen-Milles, Detlef, Kitamura, Nobuya, Klenerman, Paul, Bekken, Gry Kloumann, Knight, Stephen, Kobbe, Robin, Vasconcelos, Malte Kohns, Korten, Volkan, Kosgei, Caroline, Krawczyk, Karolina, Vecham, Pavan Kumar, Kumar, Deepali, Kurtzman, Ethan, Kutsogiannis, Demetrios, Kyriakoulis, Konstantinos, L’her, Erwan, Lachatre, Marie, Lacoste, Marie, Laffey, John, Lagrange, Marie, Laine, Fabrice, Lambert, Marc, Lamontagne, François, Langelot-Richard, Marie, Lantang, Eka Yudha, Lanza, Marina, Laouénan, Cédric, Laribi, Samira, Lariviere, Delphine, Launay, Odile, Lavie-Badie, Yoan, Law, Andrew, Le Bihan, Clément, Le Bris, Cyril, Le Coustumier, Eve, Le Falher, Georges, Le Gac, 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Maier, Lars Siegfrid, Maillet, Mylène, Maitre, Thomas, Malfertheiner, Maximilian, Malik, Nadia, Maltez, Fernando, Malvy, Denis, Mambert, Marina, Manda, Victoria, Mandei, Jose, Manning, Edmund, Manuel, Aldric, Sant, Ceila Maria, Malaque, Ana, Marino, Flávio, de Araújo Mariz, Carolline, Eid, Charbel Maroun, Marques, Ana, Marquis, Catherine, Marsh, Brian, Marsh, Laura, Marshall, John, Martelli, Celina Turchi, Martin-Blondel, Guillaume, Martin-Loeches, Ignacio, Martin-Quiros, Alejandro, Martin, Dori-Ann, Martin, Emily, Martinot, Martin, Rego, Caroline Martins, Martins, Ana, Martins, João, Martucci, Gennaro, Marwali, Eva Miranda, Jimenez, Juan Fernado Masa, Maslove, David, Mason, Sabina, Matan, Moshe, Mathieu, Daniel, Mattei, Mathieu, Matulevics, Romans, Maulin, Laurence, Mc Evoy, Natalie, Mccarthy, Aine, Mccloskey, Colin, Mcconnochie, Rachael, Mcdermott, Sherry, Mcdonald, Sarah, Mcelwee, Samuel, Mcevoy, Natalie, Mcgeer, Allison, Mcguinness, Niki, Mclean, Kenneth, Mcnicholas, Bairbre, 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Resseguier, Anne-Sophie, Revest, Matthieu, Rewa, Oleksa, Reyes, Luis Felipe, Richardson, David, Richardson, Denise, Richier, Laurent, Riera, Jordi, Rios, Ana Lúcia, Rishu, Asgar, Rispal, Patrick, Risso, Karine, Nuñez, Maria Angelica Rivera, Rizer, Nicholas, Roberto, André, Roberts, Stephanie, Robertson, David, Robineau, Olivier, Roche-Campo, Ferran, Rodari, Paola, Rodeia, Simão, Abreu, Julia Rodriguez, Roilides, Emmanuel, Rojek, Amanda, Romaru, Juliette, Roncon-Albuquerque, Roberto, Roriz, Mélanie, Rosa-Calatrava, Manuel, Rose, Michael, Rosenberger, Dorothea, Rossanese, Andrea, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Roze, Benoît, Russell, Clark, Ryckaert, Steffi, Holten, Aleksander Rygh, Choez, Xavier Sánchez, Saba, Isabela, Sadat, Musharaf, Saidani, Nadia, Salazar, Leonardo, Sales, Gabriele, Sallaberry, Stéphane, Salvator, Hélène, Sanchez-Miralles, Angel, Sanchez, Olivier, Sancho-Shimizu, Vanessa, Sandhu, Gyan, Sandulescu, Oana, Santos, Marlene, Sarfo-Mensah, Shirley, Sarton, Benjamine, Saviciute, Egle, Savvidou, Parthena, Scarsbrook, Joshua, Schermer, Tjard, Scherpereel, Arnaud, Schneider, Marion, Schroll, Stephan, Schwameis, Michael, Scott-Brown, James, Scott, Janet, Sedillot, Nicholas, Seitz, Tamara, Semaille, Caroline, Semple, Malcolm, Senneville, Eric, Sequeira, Filipa, Sequeira, Tânia, Shadowitz, Ellen, Shamsah, Mohammad, Sharma, Pratima, Shaw, Catherine, Shaw, Victoria, Shiban, Nisreen, Shime, Nobuaki, Shimizu, Hiroaki, Shimizu, Keiki, Shrapnel, Sally, Shum, Hoi Ping, Mohammed, Nassima Si, Sigfrid, Louise, Silva, Catarina, Silva, Maria Joao, Sin, Wai Ching, Skogen, Vegard, Smith, Sue, Smood, Benjamin, Smyth, Michelle, Snacken, Morgane, So, Dominic, Solis, Monserrat, Solomon, Joshua, Solomon, Tom, Somers, Emily, Sommet, Agnès, Song, Myung Jin, Song, Rima, Song, Tae, Sonntagbauer, Michael, Soum, Edouard, Uva, Maria Sousa, Sousa, Marta, Souza-Dantas, Vicente, Sperry, Alexandra, Sriskandan, Shiranee, Staudinger, Thomas, Stecher, 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Azhari, Tedder, Richard, Teixeira, João, Tellier, Marie-Capucine, Terpstra, Pleun, Terrier, Olivier, Terzi, Nicolas, Tessier-Grenier, Hubert, Thibault, V., Thiberville, Simon-Djamel, Thill, Benoît, Thompson, A., Thompson, Shaun, Thomson, David, Thomson, Emma, Thuy, Duong Bich, Thwaites, Ryan, Timashev, Peter, Timsit, Jean-François, Vijayaraghavan, Bharath Kumar Tirupakuzhi, Toki, Maria, Tonby, Kristian, Santos-Olmo, Rosario Maria Torres, Torres, Antoni, Torres, Margarida, Trioux, Théo, Trieu, Huynh Trung, Tromeur, Cécile, Trontzas, Ioannis, Troost, Jonathan, Trouillon, Tiffany, Tual, Christelle, Tubiana, Sarah, Tuite, Helen, Turtle, Lance, Twardowski, Pawel, Uchiyama, Makoto, Ullrich, Roman, Uribe, Alberto, Usman, Asad, Val-Flores, Luís, van de Velde, Stijn, van den Berge, Marcel, van Der Feltz, Machteld, van Der Vekens, Nicky, van Der Voort, Peter, van Der Werf, Sylvie, van Dyk, Marlice, van Gulik, Laura, van Hattem, Jarne, van Lelyveld, Steven, van Netten, Carolien, Vanel, Noémie, Vanoverschelde, Henk, Vauchy, Charline, Veislinger, Aurélie, Velazco, Jorge, Ventura, Sara, Verbon, Annelies, Vieira, César, Villanueva, Joy Ann, Villar, Judit, Villeneuve, Pierre-Marc, Villoldo, Andrea, van Vinh Chau, Nguyen, Visseaux, Benoit, Visser, Hannah, Vuorinen, Aapeli, Vuotto, Fanny, Wang, Chih-Hsien, Wei, Jia, Weil, Katharina, Wesselius, Sanne, Wham, Murray, Whelan, Bryan, White, Nicole, Wiedemann, Aurélie, Wille, Keith, Wils, Evert-Jan, Xynogalas, Ioannis, Suen, Jacky, Yacoub, Sophie, Yamazaki, Masaki, Yazdanpanah, Yazdan, Yelnik, Cécile, Yerkovich, Stephanie, Yokoyama, Toshiki, Yonis, Hodane, Young, Paul, Yuliarto, Saptadi, Zabbe, Marion, Zacharowski, Kai, Zahran, Maram, Zambon, Maria, Zanella, Alberto, Zawadka, Konrad, Zayyad, Hiba, Zoufaly, Alexander, Zucman, David, Abdukahil, S. 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G., Proenca, L., Puechal, O., Purcell, G., Quesada, L., Quist-Paulsen, E., Quraishi, M., Ratsep, I., Rossler, B., Rabaud, C., Rafiq, M., Ragazzo, G., Rainieri, F., Ramakrishnan, N., Ramanathan, K., Rammaert, B., Rapp, C., Rasmin, M., Rau, C., Rebaudet, S., Redl, S., Reeve, B., Reid, L., Reis, R., Remppis, J., Remy, M., Renk, H., Resende, L., Resseguier, A. -S., Revest, M., Rewa, O., Reyes, L. F., Richardson, D., Richier, L., Riera, J., Rios, A. L., Rishu, A., Rispal, P., Risso, K., Nunez, M. A. R., Rizer, N., Roberto, A., Roberts, S., Robertson, D. L., Robineau, O., Roche-Campo, F., Rodari, P., Rodeia, S., Abreu, J. R., Roilides, E., Rojek, A., Romaru, J., Roncon-Albuquerque, R., Roriz, M., Rosa-Calatrava, M., Rose, M., Rosenberger, D., Rossanese, A., Rossignol, B., Rossignol, P., Roy, C., Roze, B., Russell, C. D., Ryckaert, S., Holten, A. R., Choez, X. S., Saba, I., Sadat, M., Saidani, N., Salazar, L., Sales, G., Sallaberry, S., Salvator, H., Sanchez-Miralles, A., Sanchez, O., Sancho-Shimizu, V., Sandhu, G., Sandulescu, O., Santos, M., Sarfo-Mensah, S., Sarton, B., Saviciute, E., Savvidou, P., Scarsbrook, J., Schermer, T., Scherpereel, A., Schneider, M., Schroll, S., Schwameis, M., Scott-Brown, J., Scott, J. T., Sedillot, N., Seitz, T., Semaille, C., Semple, M. G., Senneville, E., Sequeira, F., Sequeira, T., Shadowitz, E., Shamsah, M., Sharma, P., Shaw, C. A., Shaw, V., Shiban, N., Shime, N., Shimizu, H., Shimizu, K., Shrapnel, S., Shum, H. P., Mohammed, N. S., Sigfrid, L., Silva, C., Silva, M. J., Sin, W. C., Skogen, V., Smith, S., Smood, B., Smyth, M., Snacken, M., So, D., Solis, M., Solomon, J., Solomon, T., Somers, E., Sommet, A., Song, M. J., Song, R., Song, T., Sonntagbauer, M., Soum, E., Uva, M. S., Sousa, M., Souza-Dantas, V., Sperry, A., Sriskandan, S., Staudinger, T., Stecher, S. -S., Stienstra, Y., Stiksrud, B., Streinu-Cercel, A., Strudwick, S., Stuart, A., Stuart, D., Sultana, A., Summers, C., Svistunov, M. S. A. A., Syrigos, K., Sztajnbok, J., Szuldrzynski, K., Teoule, F., Tabrizi, S., Tagherset, L., Talarek, E., Taleb, S., Talsma, J., Le Van, T., Tanaka, H., Tanaka, T., Taniguchi, H., Tardivon, C., Tattevin, P., Taufik, M. A., Tedder, R. S., Teixeira, J., Tellier, M. -C., Terpstra, P., Terrier, O., Terzi, N., Tessier-Grenier, H., Thibault, V., Thiberville, S. -D., Thill, B., Thompson, A. A. R., Thompson, S., Thomson, D., Thomson, E. C., Thuy, D. B., Thwaites, R. S., Timashev, P. S., Timsit, J. -F., Vijayaraghavan, B. K. T., Toki, M., Tonby, K., Santos-Olmo, R. M. T., Torres, A., Torres, M., Trioux, T., Trieu, H. T., Tromeur, C., Trontzas, I., Troost, J., Trouillon, T., Tual, C., Tubiana, S., Tuite, H., Turtle, L. C. W., Twardowski, P., Uchiyama, M., Ullrich, R., Uribe, A., Usman, A., Val-Flores, L., Van De Velde, S., Van Den Berge, M., Van Der Feltz, M., Van Der Vekens, N., Van Der Voort, P., Van Der Werf, S., Van Dyk, M., Van Gulik, L., Van Hattem, J., Van Lelyveld, S., Van Netten, C., Vanel, N., Vanoverschelde, H., Vauchy, C., Veislinger, A., Velazco, J., Ventura, S., Verbon, A., Vieira, C., Villanueva, J. A., Villar, J., Villeneuve, P. -M., Villoldo, A., Van Vinh Chau, N., Visseaux, B., Visser, H., Vuorinen, A., Vuotto, F., Wang, C. -H., Wei, J., Weil, K., Wesselius, S., Wham, M., Whelan, B., White, N., Wiedemann, A., Wille, K., Wils, E. -J., Xynogalas, I., Suen, J. Y., Yacoub, S., Yamazaki, M., Yazdanpanah, Y., Yelnik, C., Yerkovich, S., Yokoyama, T., Yonis, H., Young, P., Yuliarto, S., Zabbe, M., Zacharowski, K., Zahran, M., Zambon, M., Zanella, A., Zawadka, K., Zayyad, H., Zoufaly, A., Zucman, D., Apollo - University of Cambridge Repository, Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Department of Mathematics and Statistics, Wichita State University, Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This work was supported by the Department for International Development and Wellcome Trust [215091/Z/18/Z], the Bill and Melinda Gates Foundation [OPP1209135]. Country-specific support was provided by the Canadian Institutes of Health Research Coronavirus Rapid Research Funding Opportunity [OV2170359], the Health Research Board Ireland [CTN Award 2014-012], National Institute for Health Research (NIHR) [award CO-CIN-01], the Medical Research Council (MRC) [grant MC_PC_19059], the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford [award 200907], NIHR HPRU in Respiratory Infections at Imperial College London with PHE [award 200927], Liverpool Experimental Cancer Medicine Centre [grant reference C18616/A25153], NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) [FP7 project 602525], National Institutes of Health (NIH) [UL1TR002240], and NIHR Clinical Research Network infrastructure support. We acknowledge the generous support of all ISARIC Partners who have contributed data and expertise to this analysis, with or without dedicated funding. The views expressed are those of the authors and not necessarily those of the funders or institutions listed above., European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014), Infectious diseases, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Medical Research Council (MRC), National Institute for Health Research, UKRI MRC COVID-19 Rapid Response Call, UK Research and Innovation, and BOZEC, Erwan

Subjects
Male, Abdominal pain, Pediatrics, 030204 cardiovascular system & hematology, Logistic regression, 0302 clinical medicine, Diagnosis, wc_505, Medicine, ISARIC Clinical Characterisation Group, Prospective Studies, 030212 general & internal medicine, Child, wa_105, COVID-19, Case definition, SARS-CoV-2, Symptoms, Aged, Female, Hospitalization, Hospitals, Humans, Middle Aged, General Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Infectious Diseases, Cohort, Vomiting, qw_160, medicine.symptom, Life Sciences & Biomedicine, Diagnosi, Human, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Nausea, Symptom, Age and sex, Microbiology, 1117 Public Health and Health Services, 03 medical and health sciences, Hospital, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Science & Technology, business.industry, 1103 Clinical Sciences, Prospective Studie, Observational study, wf_100, business
Abstract

Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Published
2021

18. Harmonisation preserves research resources

Author

Alfredo Tagarro, Cristina Epalza, Julia Bielicki, Hanna Renk, and Malte Kohns Vasconcelos

Subjects
2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Infecciones por coronavirus, MEDLINE, Enfermedad transmisible, Virology, Article, Infectious Diseases, Investigación, Medicine, Health Resources, Humans, business
Abstract

Sin financiación 71.491 JCR (2021) Q1, 2/95 Infectious Diseases 10.236 SJR (2021) Q1, 3/301 Infectious Diseases No data IDR 2021 UEM

Published
2021

19. Infection Control and Management of COVID-19: Challenges for Paediatric Tertiary Care Hospitals

Author

Hanna Renk, Oliver Heinzel, Tina Ganzenmueller, Rupert Handgretinger, Jonathan Remppis, and Malte Kohns Vasconcelos

Subjects
Coronavirus disease 2019 (COVID-19), business.industry, Infection control, Medicine, Medical emergency, business, medicine.disease, Tertiary care
Abstract

PURPOSE: To describe infection control measures and patient management at a tertiary children’s hospital in southern Germany during the COVID-19 pandemic.METHODS: Prospective, observational study of infection control measures, patient management, clinical and virologic data of paediatric patients treated at our hospital during the COVID-19 pandemic from February to May 2020. Infection control measures were documented beginning with preparation for the pandemic. All paediatric patients with suspected SARS-CoV-2 infection were prospectively included in the study.RESULTS: With local triage, restraint of patient admission and testing strategies implemented, healthcare capacity remained adequate and no healthcare-associated infections occurred. Workload in the paediatric emergency department significantly decreased following the lockdown of schools and kindergartens. 7 of 174 (4%) children with and 2 of 208 (1%) children without typical symptoms, respectively, were diagnosed with COVID-19 by PCR. Six out of nine inpatients treated for COVID-19 had underlying comorbidities, two were admitted to the intensive care unit. One patient died shortly after discharge.CONCLUSIONS: While COVID-19 generally causes mild disease in children, severe illness and fatal cases may occur, particularly among children with underlying diseases. Tertiary children’s hospitals may face challenges with treating potential high-risk patients during the pandemic. Thus, timely establishment of effective testing and triage strategies is crucial.

Published
2020

20. SARS-CoV-2 testing and infection control strategies in European paediatric emergency departments during the first wave of the pandemic

Author

Carlo Giaquinto, Andrew Riordan, Maggie Nyirenda Nyang'wa, Malte Kohns Vasconcelos, Sigita Burokiene, Ewelina Gowin, Sarah Eisen, Jolanta Popielska, Sara Villanueva-Medina, Liviana Da Dalt, Hanna Renk, Despoina Gkentzi, Markus Hufnagel, Julia Bielicki, and Daniele Donà

Subjects
Male, Adolescent, Preparedness, Short Communication, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Disease, Pediatrics, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Clinical Protocols, 030225 pediatrics, Health care, Pandemic, medicine, Humans, Infection control, Prospective Studies, Pediatrics, Perinatology, and Child Health, 030212 general & internal medicine, Child, Survey, Pandemics, Infection Control, business.industry, Infant, Newborn, Infant, Outbreak, COVID-19, Triage, medicine.disease, preparedness, survey, triage, Test (assessment), Europe, Child, Preschool, Health Care Surveys, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Female, Medical emergency, Emergency Service, Hospital, business
Abstract

Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources.Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed. What is Known:• WHO and public health authorities issued case definitions, testing and infection control recommendations for COVID-19 in January.• SARS-CoV-2 testing was made available across Europe in February.What is New:• Paediatric emergency departments implemented COVID-19-specific procedures rapidly, including case definitions, testing guidelines and early triage.• A third of surveyed departments waited more than 24 h for SARS-CoV-2 test to be reported, resulting in additional strain on resources.

Published
2020

21. Reducing Hematologic Toxicity With Short Course Postexposure Prophylaxis With Zidovudine for HIV-1 Exposed Infants With Low Transmission Risk

Author

Susanne Schmidtke, Sandra Hertling, Martin Blohm, Robin Kobbe, Benno Kreuels, Thi Thanh Truc Nguyen, Ulf Schulze-Sturm, Prasad T. Oommen, Christina Becker, Björn-Erik Ole Jensen, Malte Kohns Vasconcelos, Jennifer Neubert, Karen Olah, Bettina Hollwitz, Hans-Jürgen Laws, and Franca Martignoni

Subjects
Microbiology (medical), Male, Pediatrics, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, Hematologic toxicity, Low transmission, medicine.disease_cause, 03 medical and health sciences, Zidovudine, 0302 clinical medicine, Pregnancy, 030225 pediatrics, medicine, Humans, Short course, 030212 general & internal medicine, Retrospective Studies, business.industry, Transmission (medicine), Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Hematologic Diseases, Infectious Disease Transmission, Vertical, Infectious Diseases, Pediatrics, Perinatology and Child Health, Female, business, medicine.drug
Abstract

Using retrospectively collected data from 383 infants born to HIV-1-infected mothers receiving antiretroviral therapy, we compared transmission rates and hematologic toxicity between infants receiving 2-week (short course) versus longer duration zidovudine postexposure prophylaxis. Short course resulted in lower hematologic toxicity without evidence of increased vertical transmission risk.

Published
2019

22. Children living with HIV in Europe: do migrants have worse treatment outcomes?

Author

Chappell, E., Kohns Vasconcelos, M., Goodall, R. L., Galli, L., Goetghebuer, T., Noguera-Julian, A., Rodrigues, L. C., Scherpbier, H., Smit, C., Bamford, A., Crichton, S., Navarro, M. L., Ramos, J. T., Warszawski, J., Spolou, V., Chiappini, E., Venturini, E., Prata, F., Kahlert, C., Marczynska, M., Marques, L., Naver, L., Thorne, C., Gibb, D. M., Giaquinto, C., Judd, A., Collins, I. J., Goodall, R., Rodrigues, L., Duff, C., Gomezpena, D., Jackson, C., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Granier, M., Labrune, P., Lachassine, E., Dollfus, C., Levine, M., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Monpoux, F., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., de Villeneuve, A., Lalande, M., de Flandres, J., Mazingue, F., Partisani, M. L., de Martino, M., Angelo Tovo, P., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Kinderziekenhuis, E., van der Kuip, M., Pajkrt, D., Scherpbier, H. J., de Boer, C., Weijsenfeld, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Henriet, S. S. V., van Aerde, M. 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H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Department of Sciences for Woman and Child's Health, Florence University, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, Infectious diseases, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, Global Health, APH - Aging & Later Life, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, 1, Elizabeth Chappell, 2 3 4, Malte Kohns Vasconcelo, L Goodall 1, Ruth, 5, Luisa Galli, 6, Tessa Goetghebuer, 9 10, Antoni Noguera-Julian 7 8, C Rodrigues 2, Laura, Scherpbier 11, Henriette, Smit 12, Colette, 1 13 14, Alasdair Bamford, 1, Siobhan Crichton, Luisa Navarro 10 15 16 17, Marissa, T Ramos 18, Jose, Warszawski 19 20, Josiane, Spolou 21, Vana, 5, Elena Chiappini, 5, Elisabetta Venturini, Prata 22, Filipa, Kahlert 23, Christian, Marczynska 24, Magdalena, Marques 25, Laura, Naver 26, Lar, Thorne 14, Claire, M Gibb 1, Diana, Giaquinto 27, Carlo, 1, Ali Judd, 1, Intira Jeannie Collin, Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC), European, Goodall, Ruth, Rodrigues, Laura, Duff, Charlotte, Gomezpena, Daniel, Jackson, Charlotte, Lundin, Rebecca, Mangiarini, Laura, Milanzi, Edith, Nardone, Alessandra, Hainaut, Marc, Van der Kelen, Evelyne, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Granier, Michèle, Labrune, Philippe, Lachassine, Eric, Dollfus, Catherine, Levine, Martine, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Monpoux, Fabrice, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, de Villeneuve, Arnaud, Lalande, Muriel, de Flandres, Jeanne, Mazingue, Françoise, Luisa Partisani, Maria, de Martino, Maurizio, Angelo Tovo, Pier, Gabiano, Clara, Carloni, Ine, Larovere, Domenico, Baldi, Francesco, Miniaci, Angela, Pession, Andrea, Badolato, Raffaele, Pantò, Grazia, Anastasio, Elisa, Montagnani, Carlotta, Bianchi, Leila, Allodi, Alessandra, Di Biagio, Antonio, Grignolo, Sara, Giacomet, Vania, Marchisio, Paola, Banderali, Giuseppe, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, DI COSTANZO, Pasquale, LO VECCHIO, Andrea, Donà, Daniele, Rampon, Osvalda, Romano, Amelia, Dodi, Icilio, Esposito, Susanna, Zuccaro, Valentina, Zanaboni, Domenico, Consolini, Rita, Bernardi, Stefania, Genovese, Orazio, Cristiano, Letizia, Mazza, Antonio, Garazzino, Silvia, Mignone, Federica, Silvestro, Erika, Portelli, Vincenzo, Pediatric surgery, Pediatrics, and Virology

Subjects
children, Europe, HIV, migrant, mortality, Adolescent, Child, Humans, Treatment Outcome, Viral Load, Anti-HIV Agents, HIV Infections, Transients and Migrants, medicine.medical_treatment, Human immunodeficiency virus (HIV), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], medicine.disease_cause, 0302 clinical medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, health care economics and organizations, Health Policy, Hazard ratio, virus diseases, Immunosuppression, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, population characteristics, 0305 other medical science, Viral load, geographic locations, education, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, 030505 public health, business.industry, Proportional hazards model, medicine.disease, Confidence interval, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Contains fulltext : 249078.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged

Published
2022

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