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1. Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial.

Author

Jacobs, Tom, Mumbiro, Vivian, Cassia, Uneisse, Zimba, Kevin, Nalwanga, Damalie, Ballesteros, Alvaro, Domínguez-Rodríguez, Sara, Tagarro, Alfredo, Madrid, Lola, Mutata, Constantine, Chitsamatanga, Moses, Bwakura-Dangarembizi, Mutsa, Passanduca, Alfeu, Buck, W, Nduna, Bwendo, Chabala, Chishala, Najjingo, Elizabeth, Musiime, Victor, Moraleda, Cinta, Colbers, Angela, Mujuru, Hilda, Rojo, Pablo, and Burger, David

Subjects
HIV, dolutegravir, drug–drug interaction, infants, rifampicin, Female, Humans, Infant, Male, Heterocyclic Compounds, 3-Ring, HIV, HIV Infections, Oxazines, Piperazines, Pyridones, Rifampin
Abstract

BACKGROUND: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. METHODS: Infants with HIV aged 1-12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. RESULTS: Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1-9.9), weight was 6.3 kg (5.6-7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0-24h 0.91 (95% confidence interval, .59-1.42), Ctrough 0.95 (0.57-1.59), Cmax 0.87 (0.57-1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough

Published
2024

2. First-Line Antituberculosis Drug Concentrations in Infants With HIV and a History of Recent Admission With Severe Pneumonia.

Author

Chabala, Chishala, Jacobs, Tom, Moraleda, Cinta, Ndaferankhande, John, Mumbiro, Vivian, Passanduca, Alfeu, Namuziya, Natasha, Nalwanga, Damalie, Musiime, Victor, Ballesteros, Alvaro, Domínguez-Rodríguez, Sara, Chitsamatanga, Moses, Cassia, Uneisse, Nduna, Bwendo, Bramugy, Justina, Sacarlal, Jahit, Madrid, Lola, Nathoo, Kusum, Colbers, Angela, Burger, David, Mulenga, Veronica, Buck, William, Mujuru, Hilda, Te Brake, Lindsey, Rojo, Pablo, Tagarro, Alfredo, and Aarnoutse, Rob

Subjects
HIV, HRZE, Tuberculosis, infants, pharmacokinetics, Adult, Infant, Humans, Antitubercular Agents, HIV Infections, Pneumonia, Reference Values
Abstract

Optimal antituberculosis therapy is essential for favorable clinical outcomes. Peak plasma concentrations of first-line antituberculosis drugs in infants with living HIV receiving WHO-recommended dosing were low compared with reference values for adults, supporting studies on increased doses of first-line TB drugs in infants.

Published
2023

3. Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change

Author

Jacobs, Tom G, Mumbiro, Vivian, Chitsamatanga, Moses, Namuziya, Natasha, Passanduca, Alfeu, Domínguez-Rodríguez, Sara, Tagarro, Alfredo, Nathoo, Kusum J, Nduna, Bwendo, Ballesteros, Alvaro, Madrid, Lola, Mujuru, Hilda A, Chabala, Chishala, Buck, W Chris, Rojo, Pablo, Burger, David M, Moraleda, Cinta, and Colbers, Angela

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Pediatric, HIV/AIDS, Infectious Diseases, Clinical Research, Clinical Trials and Supportive Activities, Pediatric AIDS, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Male, Infant, Humans, Child, Female, Lopinavir, Ritonavir, Rifampin, HIV Infections, Anti-HIV Agents, HIV Protease Inhibitors, lopinavir, infants, rifampin, HIV, tuberculosis, drug-drug interaction, EMPIRICAL Clinical Trial Group, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
Abstract

BackgroundAlthough super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment.MethodsThis was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.ResultsIn total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough

Published
2023

4. Empirical treatment against cytomegalovirus and tuberculosis in HIV-infected infants with severe pneumonia: study protocol for a multicenter, open-label randomized controlled clinical trial

Author

Rojo, Pablo, Moraleda, Cinta, Tagarro, Alfredo, Domínguez-Rodríguez, Sara, Castillo, Lola Madrid, Tato, Luis Manuel Prieto, López, Aranzazu Sancho, Manukyan, Lilit, Marcy, Olivier, Leroy, Valeriane, Nardone, Alessandra, Burger, David, Bassat, Quique, Bates, Matthew, Moh, Raoul, Iroh Tam, Pui-Ying, Mvalo, Tisungane, Magallhaes, Justina, Buck, W Chris, Sacarlal, Jahit, Musiime, Victor, Chabala, Chishala, and Mujuru, Hilda Angela

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Rare Diseases, Pneumonia, Clinical Trials and Supportive Activities, Tuberculosis, Pediatric, Patient Safety, HIV/AIDS, Clinical Research, Pneumonia & Influenza, Lung, Orphan Drug, Infectious Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Child, Clinical Trials, Phase II as Topic, Cytomegalovirus, Cytomegalovirus Infections, HIV Infections, Humans, Infant, Multicenter Studies as Topic, Randomized Controlled Trials as Topic, Treatment Outcome, Valganciclovir, Factorial, Empirical, HIV, Infants, Child mortality, Factorial randomized clinical trial, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, General & Internal Medicine, Clinical sciences, Epidemiology, Health services and systems
Abstract

BackgroundPneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and undertreated. The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children with HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia.MethodsThis is a Phase II-III, open-label randomized factorial (2 × 2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to (i) SoC, (ii) valganciclovir, (iii) TB-T, and (iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short-term (up to 15 days) and long-term (up to 1 year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM.DiscussionGiven the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions include toxicity and medication interactions, which will be evaluated with pharmacokinetics sub-studies.Trial registrationClinicalTrials.gov , NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.

Published
2022

5. Oral saliva swab reverse transcription PCR for Covid-19 in the paediatric population

Author

Moraleda, Cinta, Domínguez-Rodríguez, Sara, Mesa, Juan Miguel, García-Sánchez, Paula, de la Serna, María, Alonso-Cadenas, José Antonio, Bermejo, Amanda, Sabrido, Gema, Martínez-Campos, Leticia, González-Posada, Aránzazu Flavia, Illán-Ramos, Marta, Cobos-Carrascosa, Elena, Ballesteros, Álvaro, Galán, Juan Carlos, Llorente, Francisco, Aguilera-Alonso, David, Jiménez, Ana Belén, Catalán, Pilar, Dahdouh, Elias, Navarro, Ignacio, Fernández-Garoz, Bárbara, Mendoza, Pablo, Pérez-Jorge, Concepción, Cabezas-Fernández, Teresa, Blázquez-Gamero, Daniel, Rivas, Gonzalo, Gonzalez-Donapetry, Patricia, Sáez, Elena, Fernández-Pinero, Jovita, Lucas-Fernández, Jesús, Pérez-Ramírez, Elisa, Merino, Paloma, Miragaya, Sandra, Lorente, Jorge, Iglesias, Irene, Tagarro, Alfredo, EPICO working group, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Asociación Española de Pediatría, Universidad Europea de Madrid, Ministerio de Ciencia e Innovación (España), Moraleda, Cinta, Domínguez-Rodríguez, Sara, Mesa, Juan Miguel, García-Sánchez, Paula, Alonso-Cadenas, José Antonio, Bermejo, Amanda, Sabrido, Gema, Martínez-Campos, Leticia, Gonzlez-Posada, Aránzazu Flavia, Illán-Ramos, Marta, Cobos-Carrascosa, Elena, Aguilera-Alonso, David, Dahdouh, Elias, Blázquez-Gamero, Daniel, Gonzalez-Donapetry, Patricia, Fernández-Pinero, Jovita, Pérez-Ramírez, Elisa, Tagarro, Alfredo, Moraleda, Cinta [0000-0002-8335-903X], Domínguez-Rodríguez, Sara [0000-0003-3747-9265], Mesa, Juan Miguel [0000-0003-2338-7984], García-Sánchez, Paula [0000-0003-4866-6656], Alonso-Cadenas, José Antonio [0000-0002-7648-1336], Bermejo, Amanda [0000-0002-1568-6805], Sabrido, Gema [0000-0002-9690-261X], Martínez-Campos, Leticia [0000-0002-1493-0060], Gonzlez-Posada, Aránzazu Flavia [0000-0001-5787-9093], Illán-Ramos, Marta [0000-0003-2491-1549], Cobos-Carrascosa, Elena [0000-0001-7553-9615], Aguilera-Alonso, David [0000-0003-1017-2386], Dahdouh, Elias [0000-0003-2309-4129], Blázquez-Gamero, Daniel [0000-0001-6483-8329], Gonzalez-Donapetry, Patricia [0000-0002-6093-3254], Fernández-Pinero, Jovita [0000-0001-9919-0112], Pérez-Ramírez, Elisa [0000-0001-7701-9816], and Tagarro, Alfredo [0000-0003-2860-3455]

Subjects
Infectious Disease Medicine, SARS-CoV-2, Infecciones por coronavirus, Pediatría, COVID-19, Enfermedad transmisible, Reverse Transcription, Sensitivity and Specificity, Polymerase Chain Reaction, Microbiology, Ensayo, COVID-19 Testing, Cross-Sectional Studies, Virology, Pediatrics, Perinatology and Child Health, Humans, Prospective Studies, Child, Saliva, Molecular Biology
Abstract

8Pág. Centro de Investigación en Sanidad Animal (CISA), To evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR) compared with RT-PCR and antigen rapid diagnostic test (Ag-RDT) on nasopharyngeal swabs (NPS) for SARS-CoV-2 in children., The study was funded by: Project PI20/00095, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofounded by the European Regional Development Fund, by Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and Innovation (FIIB HUIS HHEN), and by SERMAS-Fundación para la Investigación Biomédica del Hospital 12 de Octubre. EC-C is supported by the Spanish Society of Paediatrics (Asociación Española de Pediatría); Grant COVID-19 EPICO-AEP 2020. JMM is funded by SERMAS-Fundación para la Investigación Biomédica del Hospital Infanta Sofía y del Henares and by Universidad Europea de Madrid, Spain. MdlS is funded by Grant Cantera de Investigación Santander, Fundación Universidad Europea de Madrid, Spain. ED is funded by the Juan de la Cierva–Incorporación granted by the Spanish Ministry of Science and Innovation. DB-G is funded by the Spanish Ministry of Science and Innovation—Instituto de Salud Carlos III and Fondos FEDER by ’Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 (INT20/00086)’.

Published
2022

6. Features of COVID-19 in Children During the Omicron Wave Compared With Previous Waves in Madrid, Spain

Author

Tagarro García, Alfredo, Coya, Olga N., Pérez Villena, Ana, Gal Iglesias, Beatriz, Navas, Adriana, Aguilera Alonso, David, and Moraleda, Cinta

Subjects
Microbiology (medical), Infectious Diseases, SARS-CoV-2, Spain, Infecciones por coronavirus, Pediatría, Pediatrics, Perinatology and Child Health, Enfermedad transmisible, COVID-19, Humans, Child, Pandemias
Abstract

Sin financiación 3.806 JCR (2021) Q3, 105/161 Inmunology No data IDR 2021 1.104 SJR (2021) Q1, 29/320 Pediatrics, Perinatology and Child Health No data IDR 2021 UEM

Published
2022
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7. Treatments for multi-system inflammatory syndrome in children - discharge, fever, and second-line therapies

Author

Tagarro, Alfredo, Domínguez-Rodríguez, Sara, Mesa, Juan Miguel, Epalza, Cristina, Grasa, Carlos, Iglesias-Bouzas, María Isabel, Fernández-Cooke, Elisa, Calvo, Cristina, Villaverde, Serena, Torres-Fernández, David, Méndez-Echevarria, Ana, Leoz, Inés, Fernández-Pascual, María, Saavedra-Lozano, Jesús, Soto, Beatriz, Aguilera-Alonso, David, Rivière, Jacques G, Fumadó, Victoria, Martínez-Campos, Leticia, Vivanco, Ana, Pilar-Orive, Francisco Javier, Alcalá, Pedro, Ruiz, Beatriz, López-Machín, Ana, Oltra, Manuel, Moraleda, Cinta, and EPICO Working Group

Subjects
Fever, SARS-CoV-2, Pediatrics, Perinatology and Child Health, COVID-19, Humans, Immunoglobulins, Intravenous, MIS-C, Steroids, Child, Children, Patient Discharge, Retrospective Studies
Abstract

Scarce evidence exists about the best treatment for multi-system inflammatory syndrome (MIS-C). We analyzed the effects of steroids, intravenous immunoglobulin (IVIG), and their combination on the probability of discharge over time, the probability of switching to second-line treatment over time, and the persistence of fever 2 days after treatment. We did a retrospective study to investigate the effect of different treatments on children with MIS-C from 1 March 2020 to 1 June 2021. We estimated the time-to-event probability using a Cox model weighted by propensity score to balance the baseline characteristics. Thirty of 132 (22.7%) patients were initially treated with steroids alone, 29/132 (21.9%) with IVIG alone, and 73/132 (55%) with IVIG plus steroids. The probability of early discharge was higher with IVIG than with IVIG plus steroids (hazard ratio [HR] 1.65, 95% CI 1.11-2.45, p = 0.013), but with a higher probability of needing second-line therapy compared to IVIG plus steroids (HR 3.05, 95% CI 1.12-8.25, p = 0.028). Patients on IVIG had a higher likelihood of persistent fever than patients on steroids (odds ratio [OR] 4.23, 95% CI 1.43-13.5, p = 0.011) or on IVIG plus steroids (OR 4.4, 95% CI 2.05-9.82, p 0.001). No differences were found for this endpoint between steroids or steroids plus IVIG. Conclusions: The benefits of each approach may vary depending on the outcome assessed. IVIG seemed to increase the probability of earlier discharge over time but also of needing second-line treatment over time. Steroids seemed to reduce persistent fever, and combination therapy reduced the need for escalating treatment. What is Known: • Steroids plus intravenous immunoglobulin, compared with intravenous immunoglobulin alone for multi-system inflammatory syndrome (MIS-C) might reduce the need for hemodynamic support and the duration of fever, but the certainty of the evidence is low. What is New: • Intravenous immunoglobulin, steroids, and their combination for MIS-C may have different outcomes. • In this study, intravenous immunoglobulin increased the probability of discharge over time, steroids reduced persistent fever, while combination therapy reduced the need for second-line treatments.

Published
2022

8. Evolving phenotypes of non-hospitalized patients that indicate long COVID

Author

ESTIRI, Hossein, Strasser, Zachary, Brat, Gabriel, Semenov, Yevgeniy, Patel, Chirag, Murphy, Shawn, Aaron, James, Agapito, Giuseppe, Albayrak, Adem, Alessiani, Mario, Amendola, Danilo, Anthony, Li, Aronow, Bruce, Ashraf, Fatima, Atz, Andrew, Avillach, Paul, Balshi, James, Beaulieu-Jones, Brett, Bell, Douglas, Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Sobrino, José Luis Bernal, Bernaux, Mélodie, Bey, Romain, Martínez, Alvar Blanco, Boeker, Martin, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence, Bradford, Robert, Bréant, Stéphane, Brown, Nicholas, Bryant, William, Bucalo, Mauro, Burgun, Anita, Cai, Tianxi, Cannataro, Mario, Carmona, Aldo, Caucheteux, Charlotte, Champ, Julien, Chen, Jin, Chen, Krista, Chiovato, Luca, Chiudinelli, Lorenzo, Cho, Kelly, Cimino, James, Colicchio, Tiago, Cormont, Sylvie, COSSIN, Sébastien, Craig, Jean, Bermúdez, Juan Luis Cruz, Rojo, Jaime Cruz, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Davoudi, Anahita, Devkota, Batsal, Dubiel, Julien, Esteve, Loic, Fan, Shirley, Follett, Robert, Gaiolla, Paula, Ganslandt, Thomas, Barrio, Noelia García, Garmire, Lana, Gehlenborg, Nils, GEVA, Alon, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Gutiérrez-Sacristán, Alba, Hanauer, David, Haverkamp, Christian, He, Bing, Henderson, Darren, Hilka, Martin, Holmes, John, Hong, Chuan, Horki, Petar, Huling, Kenneth, HUTCH, Meghan, Issitt, Richard, Jannot, Anne Sophie, Jouhet, Vianney, Keller, Mark, Kirchoff, Katie, Klann, Jeffrey, Kohane, Isaac, Krantz, Ian, Kraska, Detlef, Krishnamurthy, Ashok, L’Yi, Sehi, Le, Trang, Leblanc, Judith, Leite, Andressa, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, LOH, Ne Hooi Will, Lozano-Zahonero, Sara, Luo, Yuan, Lynch, Kristine, Mahmood, Sadiqa, Maidlow, Sarah, Malovini, Alberto, Mandl, Kenneth, Mao, Chengsheng, Maram, Anupama, Martel, Patricia, Masino, Aaron, Mazzitelli, Maria, Mensch, Arthur, Milano, Marianna, Minicucci, Marcos, Moal, Bertrand, Moore, Jason, Moraleda, Cinta, Morris, Jeffrey, MORRIS, Michele, Moshal, Karyn, Mousavi, Sajad, Mowery, Danielle, Murad, Douglas, Naughton, Thomas, Neuraz, Antoine, Ngiam, Kee Yuan, Norman, James, Obeid, Jihad, Okoshi, Marina, Olson, Karen, Omenn, Gilbert, Orlova, Nina, Ostasiewski, Brian, Palmer, Nathan, Paris, Nicolas, Patel, Lav, Jimenez, Miguel Pedrera, Pfaff, Emily, Pillion, Danielle, Prokosch, Hans, Prudente, Robson, González, Víctor Quirós, Ramoni, Rachel, Raskin, Maryna, RIEG, Siegbert, Domínguez, Gustavo Roig, Rojo, Pablo, Sáez, Carlos, Salamanca, Elisa, Samayamuthu, Malarkodi, Sandrin, Arnaud, Santos, Janaina, Savino, Maria, SCHRIVER, Emily, Schubert, Petra, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil, Balazote, Pablo Serrano, Serre, Patricia, Serret-Larmande, Arnaud, Shakeri, Zahra, Silvio, Domenick, Sliz, Piotr, SON, Jiyeon, Sonday, Charles, South, Andrew, Spiridou, Anastasia, Tan, Amelia, Tan, Bryce, Tan, Byorn, Tanni, Suzana, Taylor, Deanne, Terriza Torres, Ana, Tibollo, Valentina, Tippmann, Patric, Torti, Carlo, Trecarichi, Enrico, Tseng, Yi-Ju, Vallejos, Andrew, Varoquaux, Gael, Vella, Margaret, Verdy, Guillaume, Vie, Jill-Jênn, Visweswaran, Shyam, Vitacca, Michele, Wagholikar, Kavishwar, Waitman, Lemuel, Wang, Xuan, Wassermann, Demian, Weber, Griffin, XIA, Zongqi, Yehya, Nadir, Yuan, William, Zambelli, Alberto, Zhang, Harrison, Zoeller, Daniel, Zucco, Chiara, Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Service d'informatique médicale et biostatistiques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), This work was supported by the National Human Genome Research Institute grant 3U01HG008685-05S2 and the National Library of Medicine grant T15LM007092., École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), and Université Paris Cité (UPCité)

Subjects
medicine.medical_specialty, Neurological disorder, Chest pain, MESH: Phenotype, Article, 03 medical and health sciences, 0302 clinical medicine, Post-Acute COVID-19 Syndrome, Diabetes mellitus, Internal medicine, Machine learning, medicine, Chronic fatigue syndrome, Humans, Electronic health records, Post-acute sequelae of SARS-CoV-2, MESH: COVID-19, 030304 developmental biology, Retrospective Studies, 0303 health sciences, MESH: Humans, business.industry, Medical record, Type 2 Diabetes Mellitus, COVID-19, Retrospective cohort study, MESH: Retrospective Studies, General Medicine, medicine.disease, 3. Good health, Dysgeusia, Phenotypes, Phenotype, Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, medicine.symptom, business, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract

Background For some SARS-CoV-2 survivors, recovery from the acute phase of the infection has been grueling with lingering effects. Many of the symptoms characterized as the post-acute sequelae of COVID-19 (PASC) could have multiple causes or are similarly seen in non-COVID patients. Accurate identification of PASC phenotypes will be important to guide future research and help the healthcare system focus its efforts and resources on adequately controlled age- and gender-specific sequelae of a COVID-19 infection. Methods In this retrospective electronic health record (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive reverse transcription-polymerase chain reaction (RT-PCR) test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3–6 and 6–9 months after the test and by age and gender. Data from longitudinal diagnosis records stored in EHRs from Mass General Brigham in the Boston Metropolitan Area was used for the analyses. Statistical analyses were performed on data from March 2020 to June 2021. Study participants included over 96 thousand patients who had tested positive or negative for COVID-19 and were not hospitalized. Results We identified 33 phenotypes among different age/gender cohorts or time windows that were positively associated with past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records 2 months or longer after a COVID-19 RT-PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.60, 95% CI [1.94–3.46]), alopecia (OR 3.09, 95% CI [2.53–3.76]), chest pain (OR 1.27, 95% CI [1.09–1.48]), chronic fatigue syndrome (OR 2.60, 95% CI [1.22–2.10]), shortness of breath (OR 1.41, 95% CI [1.22–1.64]), pneumonia (OR 1.66, 95% CI [1.28–2.16]), and type 2 diabetes mellitus (OR 1.41, 95% CI [1.22–1.64]) is one of the most significant indicators of a past COVID-19 infection. Additionally, more new phenotypes were found with increased confidence among the cohorts who were younger than 65. Conclusions The findings of this study confirm many of the post-COVID-19 symptoms and suggest that a variety of new diagnoses, including new diabetes mellitus and neurological disorder diagnoses, are more common among those with a history of COVID-19 than those without the infection. Additionally, more than 63% of PASC phenotypes were observed in patients under 65 years of age, pointing out the importance of vaccination to minimize the risk of debilitating post-acute sequelae of COVID-19 among younger adults.

Published
2021
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9. Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Author

Le, Trang, Gutiérrez-Sacristán, Alba, Son, Jiyeon, Hong, Chuan, South, Andrew, Beaulieu-Jones, Brett, Loh, Ne Hooi Will, Luo, Yuan, Morris, Michele, Ngiam, Kee Yuan, Patel, Lav, Samayamuthu, Malarkodi, Schriver, Emily, Tan, Amelia, Moore, Jason, Cai, Tianxi, Omenn, Gilbert, Avillach, Paul, Kohane, Isaac, Visweswaran, Shyam, Mowery, Danielle, Xia, Zongqi, Aaron, James, Agapito, Giuseppe, Albayrak, Adem, Alessiani, Mario, Amendola, Danilo, Angoulvant, François, Anthony, Li, Aronow, Bruce, Atz, Andrew, Balshi, James, Bell, Douglas, Bellasi, Antonio, Bellazzi, Riccardo, Benoit, Vincent, Beraghi, Michele, Bernal Sobrino, José Luis, Bernaux, Mélodie, Bey, Romain, Blanco Martínez, Alvar, Boeker, Martin, Bonzel, Clara-Lea, Booth, John, Bosari, Silvano, Bourgeois, Florence, Bradford, Robert, Brat, Gabriel, Bréant, Stéphane, Brown, Nicholas, Bryant, William, Bucalo, Mauro, Burgun, Anita, Cannataro, Mario, Carmona, Aldo, Caucheteux, Charlotte, Champ, Julien, Chen, Krista, Chen, Jin, Chiovato, Luca, Chiudinelli, Lorenzo, Cimino, James, Colicchio, Tiago, Cormont, Sylvie, Cossin, Sébastien, Craig, Jean, Cruz Bermúdez, Juan Luis, Cruz Rojo, Jaime, Dagliati, Arianna, Daniar, Mohamad, Daniel, Christel, Davoudi, Anahita, Devkota, Batsal, Dubiel, Julien, Esteve, Loic, Fan, Shirley, Follett, Robert, Gaiolla, Paula, Ganslandt, Thomas, García Barrio, Noelia, Garmire, Lana, Gehlenborg, Nils, Geva, Alon, Gradinger, Tobias, Gramfort, Alexandre, Griffier, Romain, Griffon, Nicolas, Grisel, Olivier, Hanauer, David, Haverkamp, Christian, He, Bing, Henderson, Darren, Hilka, Martin, Holmes, John, Horki, Petar, Huling, Kenneth, Hutch, Meghan, Issitt, Richard, Jannot, Anne Sophie, Jouhet, Vianney, Kavuluru, Ramakanth, Keller, Mark, Kirchoff, Katie, Klann, Jeffrey, Krantz, Ian, Kraska, Detlef, Krishnamurthy, Ashok, L’yi, Sehi, Leblanc, Judith, Leite, Andressa, Lemaitre, Guillaume, Lenert, Leslie, Leprovost, Damien, Liu, Molei, Lozano-Zahonero, Sarah, Lynch, Kristine, Mahmood, Sadiqa, Maidlow, Sarah, Makoudjou Tchendjou, Adeline, Malovini, Alberto, Mandl, Kenneth, Mao, Chengsheng, Maram, Anupama, Martel, Patricia, Masino, Aaron, Matheny, Michael, Maulhardt, Thomas, Mazzitelli, Maria, Mcduffie, Michael, Mensch, Arthur, Ashraf, Fatima, Milano, Marianna, Minicucci, Marcos, Moal, Bertrand, Moraleda, Cinta, Morris, Jeffrey, Moshal, Karyn, Mousavi, Sajad, Murad, Douglas, Murphy, Shawn, Naughton, Thomas, Neuraz, Antoine, Norman, James, Obeid, Jihad, Okoshi, Marina, Olson, Karen, Orlova, Nina, Ostasiewski, Brian, Palmer, Nathan, Paris, Nicolas, Pedrera Jimenez, Miguel, Pfaff, Emily, Pillion, Danielle, Prokosch, Hans, Prudente, Robson, Quirós González, Víctor, Ramoni, Rachel, Raskin, Maryna, Rieg, Siegbert, Roig Domínguez, Gustavo, Rojo, Pablo, Sáez, Carlos, Salamanca, Elisa, Sandrin, Arnaud, Santos, Janaina, Savino, Maria, Schuettler, Juergen, Scudeller, Luigia, Sebire, Neil, Balazote, Pablo Serrano, Serre, Patricia, Serret-Larmande, Arnaud, Shakeri, Zahra, Silvio, Domenick, Sliz, Piotr, Sonday, Charles, Spiridou, Anastasia, Tan, Bryce, Tan, Byorn, Tanni, Suzana, Taylor, Deanne, Terriza-Torres, Ana, Tibollo, Valentina, Tippmann, Patric, Torti, Carlo, Trecarichi, Enrico, Tseng, Yi-Ju, Vallejos, Andrew, Varoquaux, Gael, Vella, Margaret, Vie, Jill-Jênn, Vitacca, Michele, Wagholikar, Kavishwar, Waitman, Lemuel, Wassermann, Demian, Weber, Griffin, William, Yuan, Yehya, Nadir, Zambelli, Alberto, Zhang, Harrison, Zoeller, Daniela, Zucco, Chiara, Unité d'informatique médicale, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), AS is funded by National Institutes of Health (NIH) National Heart Lung, and Blood Institute (NHLBI) K23HL148394 and L40HL148910, and NIH-National Center for Advancing Translational Sciences (NCATS) UL1TR001420. JM is funded by NIH-National Institute of Allergy and Infectious Disease (NIAD) AI11679. LP is funded by NCATS Clinical and Translational Science Award (CTSA) Number UL1TR002366. GO is funded by NIH National Institute of Environmental Health Sciences (NIEHS) P30ES017885 and National Cancer Institute (NCI) U24CA210967. SV is funded by NIH-National Library of Medicine (NLM) R01LM012095 and NCATS UL1TR001857. DM is funded by NCATS CTSA Number UL1-TR001878. ZX is funded by NIH National Institute of Neurological Disorders and Stroke (NINDS) R01NS098023., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Cancer Institute, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), University of Pennsylvania Perelman School of Medicine, Harvard Medical School, University of Pittsburgh, Wake Forest School of Medicine, National University Health Systems, Northwestern University, University of Kansas Medical Center, University of Pennsylvania Health System, University of Michigan, University of Kentucky, University Magna Graecia of Catanzaro, INC., Lombardia Region Health System, Universidade Estadual Paulista (UNESP), Assistance Publique-Hôpitaux de Paris, Tan Tock Seng Hospital, University of Cincinnati, Medical University of South Carolina, St. Luke’s University Health Network, David Geffen School of Medicine at UCLA, ASST Papa Giovanni XXIII, University of Pavia, APHP Greater Paris University Hospital, ASST Pavia, Hospital Universitario, University of Freiburg, Informatics and Virtual Environments (DRIVE), IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, University of North Carolina, BIOMERIS (BIOMedical Research Informatics Solutions), CEA, LIRMM, Boston Children’s Hospital, Istituti Clinici Scientifici Maugeri SpA SB IRCCS, University of Alabama at Birmingham, Bordeaux University Hospital/ERIAS-Inserm U1219 BPH, Children’s Hospital of Philadelphia, Inria Centre de Paris, Heidelberg University, and Pain Medicine Boston Children’s Hospital, University of Michigan Medical School, MSHI Medical University of South Carolina, Massachusetts General Hospital, The Children’s Hospital of Philadelphia, University Hospital, Clevy.io, Harvard T.H. Chan School of Public Health, VA Salt Lake City Health Care System, Veterans Affairs Medical Center, PSL Université Paris, School of Biomedical Informatics, Great Ormond Street Hospital for Children, University of Erlangen-Nürnberg, Office of Research and Development, Universitat Politècnica de València, Nurse Department of FMB-Medicine School of Botucatu, FAU Erlangen-Nürnberg, National University Hospital, Chang Gung University, Medical College of Wisconsin, McGill University, Inria Lille, ICS S Maugeri IRCCS, University of Missouri, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), and Université Paris Cité (UPC)

Subjects
Male, Epidemiology, Cross-sectional study, Disease, Severity of Illness Index, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Child, Prevalence, MESH: COVID-19, 030212 general & internal medicine, Young adult, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Multidisciplinary, MESH: Infant, Newborn, Middle Aged, MESH: Infant, 3. Good health, Neurology, MESH: Young Adult, Child, Preschool, Medicine, Female, Encephalitis, Adult, MESH: Pandemics, medicine.medical_specialty, Adolescent, Science, Myelitis, MESH: Nervous System Diseases, Article, Young Adult, 03 medical and health sciences, Medical research, MESH: Cross-Sectional Studies, MESH: Severity of Illness Index, Internal medicine, Severity of illness, medicine, Humans, Pandemics, MESH: Prevalence, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, Newborn, COVID-19, Infant, MESH: Adult, medicine.disease, MESH: Male, Confidence interval, Cross-Sectional Studies, Relative risk, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Nervous System Diseases, business, MESH: Female, Neurological disorders, 030217 neurology & neurosurgery
Abstract

Made available in DSpace on 2022-04-29T08:35:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Division of Intramural Research, National Institute of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases National Institute of Allergy and Infectious Diseases National Center for Advancing Translational Sciences National Heart, Lung, and Blood Institute National Institute of Environmental Health Sciences U.S. National Library of Medicine National Institute of Neurological Disorders and Stroke Division of Cancer Prevention, National Cancer Institute Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease. Department of Biostatistics Epidemiology and Informatics University of Pennsylvania Perelman School of Medicine Department of Biomedical Informatics Harvard Medical School Department of Neurology University of Pittsburgh, Biomedical Science Tower 3, Suite 7014, 3501 5th Avenue Department of Pediatrics Wake Forest School of Medicine Department of Critical Care National University Health Systems Department of Preventive Medicine Northwestern University Department of Biomedical Informatics University of Pittsburgh Department of Surgery National University Health Systems Department of Internal Medicine University of Kansas Medical Center Data Analytics Center University of Pennsylvania Health System Department of Computational Medicine and Bioinformatics University of Michigan Department of Biomedical Informatics University of Kentucky Department of Legal Economic and Social Sciences University Magna Graecia of Catanzaro Health Catalyst INC. Department of Surgery ASST Pavia Lombardia Region Health System Clinical Research Unit of Botucatu Medical School São Paulo State University Pediatric Emergency Department Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris National Center for Infectious Diseases Tan Tock Seng Hospital Departments of Biomedical Informatics Pediatrics Cincinnati Children’s Hospital Medical Center University of Cincinnati Department of Pediatrics Medical University of South Carolina Department of Surgery St. Luke’s University Health Network Department of Medicine David Geffen School of Medicine at UCLA UOC Ricerca Innovazione e Brand Reputation ASST Papa Giovanni XXIII Department of Electrical Computer and Biomedical Engineering University of Pavia IT Department Innovation & Data APHP Greater Paris University Hospital I.T. Department ASST Pavia Health Informatics Hospital Universitario, 12 de Octubre Strategy and Transformation Department APHP Greater Paris University Hospital Faculty of Medicine and Medical Center University of Freiburg Digital Research Informatics and Virtual Environments (DRIVE), Great Ormond Street Hospital for Children Scientific Direction IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano North Carolina Translational and Clinical Sciences (NC TraCS) Institute University of North Carolina BIOMERIS (BIOMedical Research Informatics Solutions) Department of Biomedical Informatics HEGP APHP Greater Paris University Hospital Department of Medical and Surgical Sciences Data Analytics Research Center University Magna Graecia of Catanzaro Department of Anesthesia St. Luke’s University Health Network Université Paris-Saclay Inria CEA INRIA Sophia-Antipolis–ZENITH Team LIRMM Computational Health Informatics Program Boston Children’s Hospital Department of Internal Medicine University of Kentucky Unit of Internal Medicine and Endocrinology Istituti Clinici Scientifici Maugeri SpA SB IRCCS Department of Internal Medicine and Therapeutics University of Pavia Informatics Institute University of Alabama at Birmingham IAM Unit Bordeaux University Hospital/ERIAS-Inserm U1219 BPH Biomedical Informatics Center Medical University of South Carolina Clinical Research Informatics Boston Children’s Hospital Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia SED/SIERRA Inria Centre de Paris Health Information Technology & Services University of Michigan Internal Medicine Department Botucatu Medical School São Paulo State University Heinrich-Lanz-Center for Digital Health University Medicine Mannheim Heidelberg University Department of Anesthesiology Critical Care and Pain Medicine Boston Children’s Hospital Department of Learning Health Sciences University of Michigan Medical School MSHI Medical University of South Carolina Department of Medicine Massachusetts General Hospital Division of Human Genetics Department of Pediatrics The Children’s Hospital of Philadelphia Center for Medical Information and Communication Technology University Hospital Renaissance Computing Institute/Department of Computer Science University of North Carolina Clinical Research Unit Saint Antoine Hospital APHP Greater Paris University Hospital Clevy.io Department of Biostatistics Harvard T.H. Chan School of Public Health VA Informatics and Computing Infrastructure VA Salt Lake City Health Care System MICHR Informatics University of Michigan Laboratory of Informatics and Systems Engineering for Clinical Research Istituti Clinici Scientifici Maugeri SpA SB IRCCS Harvard Catalyst Harvard Medical School Clinical Research Unit Paris Saclay APHP Greater Paris University Hospital Department of Anesthesiology and Critical Care Children’s Hospital of Philadelphia VA Informatics and Computing Infrastructure Tennessee Valley Healthcare System Veterans Affairs Medical Center École Normale Supérieure PSL Université Paris BIG-ARC The University of Texas Health Science Center at Houston School of Biomedical Informatics Pediatric Infectious Disease Department Hospital Universitario, 12 de Octubre Department of Infectious Diseases Great Ormond Street Hospital for Children Department of Neurology Massachusetts General Hospital Internal Medicine Department of Botucatu Medical School São Paulo State University Department of Pediatrics Boston Children’s Hospital Center for Biomedical Informatics Wake Forest School of Medicine Department of Medical Informatics University of Erlangen-Nürnberg Department of Veterans Affairs Office of Research and Development Biomedical Data Science Lab ITACA Institute Universitat Politècnica de València Nurse Department of FMB-Medicine School of Botucatu Management Engineering ASST Pavia Lombardia Region Health System Department of Anesthesiology University Hospital Erlangen FAU Erlangen-Nürnberg Critical Care Medicine Department of Medicine St. Luke’s University Health Network Department of Medicine National University Hospital Department of Information Management Chang Gung University Clinical & Translational Science Institute Medical College of Wisconsin Montréal Neurological Institute McGill University SequeL Inria Lille Respiratory Department ICS S Maugeri IRCCS Department of Health Management and Informatics University of Missouri Department of Oncology ASST Papa Giovanni XXIII Clinical Research Unit of Botucatu Medical School São Paulo State University Internal Medicine Department Botucatu Medical School São Paulo State University Internal Medicine Department of Botucatu Medical School São Paulo State University Division of Intramural Research, National Institute of Allergy and Infectious Diseases: AI11679 Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases: AI11679 National Institute of Allergy and Infectious Diseases: AI11679 National Center for Advancing Translational Sciences: CTSA Award #UL1TR001878 National Center for Advancing Translational Sciences: CTSA Award #UL1TR002366 National Heart, Lung, and Blood Institute: K23HL148394 National Institute of Environmental Health Sciences: P30ES017885 U.S. National Library of Medicine: R01LM012095 National Institute of Neurological Disorders and Stroke: R01NS098023 Division of Cancer Prevention, National Cancer Institute: U24CA210967 National Center for Advancing Translational Sciences: UL1TR001420 National Center for Advancing Translational Sciences: UL1TR001857

Published
2021
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10. Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children

Author

Tagarro, Alfredo, Cobos-Carrascosa, Elena, Villaverde, Serena, Sanz-Santaeufemia, Francisco-Javier, Grasa, Carlos, Soriano-Arandes, Antoni, Hernanz, Alicia, Navarro, María Luisa, Pino, Rosa, Epalza, Cristina, Batista, Rosa, Rizo, Jana, Iglesias-Bouzas, María-Isabel, Rodríguez-Molino, Paula, Villanueva-Medina, Sara, Carrasco-Colom, Jaime, Alonso-Cadenas, José-Antonio, Mellado, María-José, Herrero, Blanca, Melendo, Susana, De La Torre, Mercedes, Calleja, Lourdes, Calvo, Cristina, Urretavizcaya-Martínez, María, Astigarraga, Itziar, Menasalvas, Ana, Penin, María, Neth, Olaf, Berzosa, Arantxa, De Ceano-Vivas, María, Vidal, Paula, Romero, Isabel, González, Raúl, García, María Luz, Mesa, Juan-Miguel, Ballesteros, Álvaro, Bernardino, María, Moraleda, Cinta, and EPICO-AEP Working Group

Subjects
Diagnóstico clínico, Pediatrics, medicine.medical_specialty, Adolescent, Infecciones por coronavirus, Enfermedad transmisible, MIS-C, Disease, Asymptomatic, Severity, Medicina preventiva, Risk Factors, medicine, Humans, Prospective Studies, Prospective cohort study, Children, Asthma, business.industry, SARS-CoV-2, Pediatría, COVID-19, Clinical phenotypes, medicine.disease, Systemic Inflammatory Response Syndrome, Pneumonia, Upper respiratory tract infection, Pediatrics, Perinatology and Child Health, Cohort, Bronchitis, Original Article, medicine.symptom, business
Abstract

We aimed to identify the spectrum of disease in children with COVID-19, and the risk factors for admission in paediatric intensive care units (PICUs). We conducted a multicentre, prospective study of children with SARS-CoV-2 infection in 76 Spanish hospitals. We included children with COVID-19 or multi-inflammatory syndrome (MIS-C) younger than 18 years old, attended during the first year of the pandemic. We enrolled 1200 children. A total of 666 (55.5%) were hospitalised, and 123 (18.4%) required admission to PICU. Most frequent major clinical syndromes in the cohort were mild syndrome (including upper respiratory tract infection and flu-like syndrome, skin or mucosae problems and asymptomatic), 44.8%; bronchopulmonary syndrome (including pneumonia, bronchitis and asthma flare), 18.5%; fever without a source, 16.2%; MIS-C, 10.6%; and gastrointestinal syndrome, 10%. In hospitalised children, the proportions were 28.5%, 25.7%, 16.5%, 19.1% and 10.2%, respectively. Risk factors associated with PICU admission were age in months (OR: 1.007; 95% CI 1.004 to 1.01), MIS-C (OR: 14.4, 95% CI 8.9 to 23.8), chronic cardiac disease (OR: 4.8, 95% CI 1.8 to 13), asthma or recurrent wheezing (OR: 2.5, 95% CI 1.2 to 5.2) and after excluding MIS-C patients, moderate/severe liver disease (OR: 8.6, 95% CI 1.6 to 47.6). However, asthmatic children were admitted into the PICU due to MIS-C or pneumonia, not due to asthma flare.Conclusion: Hospitalised children with COVID-19 usually present as one of five major clinical phenotypes of decreasing severity. Risk factors for PICU include MIS-C, elevation of inflammation biomarkers, asthma, moderate or severe liver disease and cardiac disease. What is Known: • All studies suggest that children are less susceptible to serious SARS-CoV-2 infection when compared to adults. Most studies describe symptoms at presentation. However, it remains unclear how these symptoms group together into clinically identifiable syndromes and the severity associated with them. What is New: • We have gathered the primary diagnoses into five major syndromes of decreasing severity: MIS-C, bronchopulmonary syndrome, gastrointestinal syndrome, fever without a source and mild syndrome. Classification of the children in one of the syndromes is unique and helps to assess the risk of critical illness and to define the spectrum of the disease instead of just describing symptoms and signs. Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness (PI20/00095) SERMAS-Fundacion para la Investigacion Biomedica del Hospital 12 de Octubre Spanish Society of Paediatrics (Asociacion Espanola de Pediatria) Instituto de Salud Carlos III Spanish Government Fondos FEDER (Contrato Rio Hortega) CM20/00173 Becas Cantera Santander-Fundacion Universidad Europea de Madrid 3.860 JCR (2021) Q1, 28/130 Pediatrics 0.806 SJR (2021) Q1, 65/320 Pediatrics, Perinatology and Child Health No data IDR 2021 UEM

Published
2021

11. Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Author

Li, You, Reeves, Rachel M., Wang, Xin, Bassat, Quique, Brooks, W. Abdullah, Cohen, Cheryl, Moore, David P., Nunes, Marta, Rath, Barbara, Campbell, Harry, Nair, Harish, Acacio, Sozinho, Alonso, Wladimir J., Antonio, Martin, Ayora Talavera, Guadalupe, Badarch, Darmaa, Baillie, Vicky L., Barrera-Badillo, Gisela, Bigogo, Godfrey, Broor, Shobha, Bruden, Dana, Buchy, Philippe, Byass, Peter, Chipeta, James, Clara, Wilfrido, Dang, Duc-Anh, de Freitas Lazaro Emediato, Carla Cecilia, de Jong, Menno, Diaz-Quinonez, Jose Alberto, Do, Lien Anh Ha, Fasce, Rodrigo A., Feng, Luzhao, Ferson, Mark J., Gentile, Angela, Gessner, Bradford D., Goswami, Doli, Goyet, Sophie, Grijalva, Carlos G., Halasa, Natasha, Hellferscee, Orienka, Hessong, Danielle, Homaira, Nusrat, Jara, Jorge, Kahn, Kathleen, Khuri-Bulos, Najwa, Kotloff, Karen L., Lanata, Claudio F., Lopez, Olga, Lopez Bolanos, Maria Renee, Lucero, Marilla G., Lucion, Florencia, Lupisan, Socorro P., Madhi, Shabir A., McCracken, John P., Mekgoe, Omphile, Moraleda, Cinta, Moyes, Jocelyn, Mulholland, Kim, Munywoki, Patrick K., Naby, Fathima, Thanh Hung Nguyen, Nicol, Mark P., Nokes, D. James, Noyola, Daniel E., Onozuka, Daisuke, Palani, Nandhini, Poovorawan, Yong, Rahman, Mustafizur, Ramaekers, Kaat, Romero, Candice, Schlaudecker, Elizabeth P., Schweiger, Brunhilde, Seidenberg, Phil, Simoes, Eric A. F., Singleton, Rosalyn, Sistla, Sujatha, Sturm-Ramirez, Katharine, Suntronwong, Nungruthai, Sutanto, Agustinus, Tapia, Milagritos D., Thamthitiwat, Somsak, Thongpan, Ilada, Tillekeratne, Gayani, Tinoco, Yeny O., Treurnicht, Florette K., Turner, Claudia, Turner, Paul, van Doorn, Rogier, Van Ranst, Marc, Visseaux, Benoit, Waicharoen, Sunthareeya, Wang, Jianwei, Yoshida, Lay-Myint, Zar, Heather J., Shi, Ting, Zhang, Shanshan, Openshaw, Peter, Wedzicha, Jadwicha, Falsey, Ann, Miller, Mark, Beutels, Philippe, Bont, Louis, Pollard, Andrew, Molero, Eva, Martinon-Torres, Federico, Heikkinen, Terho, Meijer, Adam, Fischer, Thea Kolsen, van den Berge, Maarten, Giaquinto, Carlo, Mikolajczyk, Rafael, Hackett, Judy, Dillon, Laura, Tafesse, Eskinder, Cai, Bing, Knirsch, Charles, Lopez, Antonio Gonzalez, Dieussaert, Ilse, Dermateau, Nadia, Leach, Amanda, Stoszek, Sonia K., Gallichan, Scott, Kieffer, Alexia, Demont, Clarisse, Denouel, Angeline, Cheret, Arnaud, Gavart, Sandra, Aerssens, Jeroen, Wyffels, Veronique, Cleenewerck, Matthias, Fuentes, Robert, Rosen, Brian, RSV Global Epidemiology Network, RESCEU Investigators, Groningen Research Institute for Asthma and COPD (GRIAC), Ramaekers, Kaat, Van Ranst, Marc, RSV Global Epidemiology Network and RESCEU investigators, VU University medical center, APH - Global Health, Graduate School, Medical Microbiology and Infection Prevention, and AII - Infectious diseases

Subjects
Male, Respiratory diseases, Epidemiology, viruses, RESCEU investigators, EPIDEMICS, 030231 tropical medicine, Respiratory Syncytial Virus Infections, Global Health, Virus, Malalties de l'aparell respiratori, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Human metapneumovirus, Parainfluenza virus, Influenza, Human, DRIVERS, Humans, RSV Global Epidemiology Network, Metapneumovirus, 030212 general & internal medicine, Respiratory system, Epidemiologia, Paramyxoviridae Infections, biology, lcsh:Public aspects of medicine, virus diseases, lcsh:RA1-1270, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, respiratory system, biology.organism_classification, Virology, respiratory tract diseases, 3. Good health, SEASONALITY, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Influenza A virus, INFECTIONS, Respiratory Syncytial Virus, Human, Respiratory virus, Female, Human medicine, RC
Abstract

BACKGROUND: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (

Published
2019
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12. Multi-inflammatory Syndrome in Children Related to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Spain

Author

Moraleda, Cinta, Serna-Pascual, Miquel, Soriano-Arandes, Antoni, Simó, Silvia, Epalza, Cristina, Santos, Mar, Grasa, Carlos, Rodríguez, Maria, Soto, Beatriz, Gallego, Nerea, Ruiz, Yolanda, Urretavizcaya-Martínez, María, Pareja, Marta, Sanz-Santaeufemia, Francisco José, Fumadó, Victoria, Lanaspa, Miguel, Jordan, Iolanda, Prieto, Luis, Belda, Sylvia, Toral-Vázquez, Belén, Rincón, Elena, Gil-Villanueva, Nuria, Méndez-Echevarría, Ana, Castillo-Serrano, Ana, Rivière, Jacques G, Soler-Palacín, Pere, Rojo, Pablo, Tagarro, Alfredo, del Valle, Rut, Barrios, Ana, Villanueva, Sara, Contreras, Jesús R, Gutiérrez, Lourdes, Calvo, Cristina, Molino, Paula R, José Mellado, María, de Ceano, María, Penin, María, Villaverde, Serena, José Pérez, María, Otheo, Enrique, Dolores Falcón, María, Neth, Olaf, Olbrich, Peter, Goycoechea, Walter, Martín, Laura, Isabel Iglesias, María, Antonio Alonso Cadenas, José, Herrero, Blanca, Cobo, Elvira, Tovizi, Mariam, Galán, Pilar, Guillén, Sara, Navas, Adriana, Luz García-García, M, Llorente, Marta, Pérez, Sara, Figueroa, Lucía, Bermejo, Amanda, Mendoza, Pablo, Sabrido, Gema, José Hernández, María, Belén Jiménez, Ana, Berzosa, Arantxa, Illán, Marta, Bernardino, María, Jensen, Julia, Vidal, Paula, Domínguez, Sara, Ocaña, Angustias, Romero, Isabel, Fernanda Guzmán, María, Pascual, M J, López Machín, Ana, Ruiz, Beatriz, Menasalvas, Ana, Méndez, María, Hurtado, Ángela, Ara, Fátima, Cabañas, Fernando, Oltra, Manuel, Villarroya, Álvaro, Sánchez-Códez, María, Montesinos, Elena, Herranz Aguirre, Mercedes, Rius, Neus, Gómez, Alba, Bretón, Rafael, Rodríguez-Benjumea, Margarita, Campos, Ana, and García Reymundo, Mercedes

Subjects
0301 basic medicine, endocrine system diseases, viruses, Multisystem inflammatory syndrome, Enfermedad transmisible, Kawasaki's disease, multisystem inflammatory syndrome, medicine.disease_cause, pediatric inflammatory multisystemic syndrome, 0302 clinical medicine, Epidemiology, 030212 general & internal medicine, skin and connective tissue diseases, Child, Coronavirus, Kawasaki disease, Brief Report, Pediatría, virus diseases, Syndrome, SARS-CoV-2, Systemic Inflammatory Response Syndrome, AcademicSubjects/MED00290, Infectious Diseases, Síndrome mucocutáneo linfonodular, COVID-19, Microbiology (medical), 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Infecciones por coronavirus, 030106 microbiology, macromolecular substances, 03 medical and health sciences, medicine, otorhinolaryngologic diseases, Humans, business.industry, fungi, medicine.disease, body regions, Systemic inflammatory response syndrome, Spain, Immunology, business, Pediatric inflammatory multisystemic syndrome
Abstract

Some clusters of children with a multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. We describe the epidemiological and clinical features of children with MIS-C in Spain. MIS-C is a potentially severe condition that presents in children with recent SARS-CoV-2 infection. Sin financiación 9.079 JCR (2020) Q1, 18/162 Immunology 3.440 SJR (2020) Q1, 11/292 Infectious Diseases No data IDR 2019 UEM

Published
2021

13. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study

Author

Shi, Ting, McAllister, David, O'Brien, Katherine, Simoes, Eric, Madhi, Shabir, Gessner, Bradford, Polack, Fernando, Balsells, Evelyn, Acacio, Sozinho, Aguayo, Claudia, Alassani, Issifou, Ali, Asad, Antonio, Martin, Awasthi, Shally, Awori, Juliet, Azziz-Baumgartner, Eduardo, Baggett, Henry, Baillie, Vicky, Balmaseda, Angel, Barahona, Alfredo, Basnet, Sudha, Bassat, Quique, Basualdo, Wilma, Bigogo, Godfrey, Bont, Louis, Breiman, Robert, Brooks, W Abdullah, Broor, Shobha, Bruce, Nigel, Bruden, Dana, Buchy, Philippe, Campbell, Stuart, Carosone-Link, Phyllis, Chadha, Mandeep, Chipeta, James, Chou, Monidarin, Clara, Wilfrido, Cohen, Cheryl, de Cuellar, Elizabeth, Dang, Duc-Anh, Dash-Yandag, Budragchaagiin, Deloria-Knoll, Maria, Dherani, Mukesh, Eap, Tekchheng, Ebruke, Bernard, Echavarria, Marcela, de Freitas Lázaro Emediato, Carla Cecília, Fasce, Rodrigo, Feikin, Daniel, Feng, Luzhao, Gentile, Angel, Gordon, Aubree, Goswami, Doli, Goyet, Sophie, Groome, Michelle, Halasa, Natasha, Hirve, Siddhivinayak, Homaira, Nusrat, Howie, Stephen, Jara, Jorge, Jroundi, Imane, Kartasasmita, Cissy, Khuri-Bulos, Najwa, Kotloff, Karen, Krishnan, Anand, Libster, Romina, Lopez, Olga, Lucero, Marilla, Lucion, Florencia, Lupisan, Socorro, Marcone, Debora, McCracken, John, Mejia, Mario, Moisi, Jennifer, Montgomery, Joel, Moore, David, Moraleda, Cinta, Moyes, Jocelyn, Munywoki, Patrick, Mutyara, Kuswandewi, Nicol, Mark, Nokes, James, Nymadawa, Pagbajabyn, da Costa Oliveira, Maria, Oshitani, Histoshi, Pandey, Nitin, Paranhos-Baccalà, Gláucia, Phillips, Lia, Picot, Valentina Sanchez, Rahman, Mustafizur, Rakoto-Andrianarivelo, Mala, Rasmussen, Zeba, Rath, Barbara, Robinson, Annick, Romero, Candice, Russomando, Graciela, Salimi, Vahid, Sawatwong, Pongpun, Scheltema, Nienke, Schweiger, Brunhilde, Scott, J Anthony G, Seidenberg, Phil, Shen, Kunling, Singleton, Rosalyn, Sotomayor, Viviana, Strand, Tor, Sutanto, Agustinus, Sylla, Maria, Tapia, Milagritos, Thamthitiwat, Somsak, Thomas, Elizabeth, Tokarz, Rafal, Turner, Claudia, Venter, Marietjie, Waicharoen, Sunthareeya, Wang, Jianwei, Watthanaworawit, Wanitda, Yoshida, Lay-Myint, Yu, Hongjie, Zar, Heather, Campbell, Harry, Nair, Harish, University of Edinburgh, University of Glasgow, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), University of Colorado Anschutz [Aurora], University of the Witwatersrand [Johannesburg] (WITS), Agence de Médecine Préventive, Ministry of Health [Togo], Aga Khan University, Medical Research Council Unit The Gambia (MRC), King George's Medical University, Kenya Medical Research Institute (KEMRI), International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Ministry of Public Health [Thailand], Ministry of Health [Nicaragua] (MINSA), Centre for International Health [Bergen, Norway], University of Bergen (UiB), Universitat de Barcelona (UB), University Medical Center [Utrecht], Emory Global Health Institute [Atlanta] (EGHI), Emory University [Atlanta, GA], All India Institute of Medical Sciences, University of Liverpool, University of Health Sciences [Phnom-Penh, Cambodia] (UHS), Centers for Disease Control and Prevention, National Institute of Hygiene and Epidemiology [Hanoi, Vietnam] (NIHE), Réseau International des Instituts Pasteur (RIIP), National Pediatric Hospital, University of Health Sciences – Cambodia, Public Health Institute of Chile, Austral University, University of Michigan [Ann Arbor], University of Michigan System, Vanderbilt University [Nashville], KEM Hospital Research Center, University of Auckland [Auckland], Universidad del Valle de Guatemala, The University of Jordan (JU), Research Institute for Tropical Medicine, University of Cape Town, Tohoku University Graduate School of Medicine, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Rollins School of Public Health, Centre d’Infectiologie Charles-Mérieux, Université d’Antananarivo - Madagascar, Université d'Antananarivo, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Universidad Nacional de Asunción [Paraguay] (UNA), Tehran University of Medical Sciences (TUMS), Robert Koch Institute [Berlin] (RKI), The University of New Mexico [Albuquerque], Columbia Mailman School of Public Health, Columbia University [New York], University of Pretoria [South Africa], China Academy of Chinese Medical Sciences, Nagasaki University, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Statistical, Incidence, Medical virology, Infant, Newborn, Respiratory infections, Infant, Articles, Virologia mèdica, Infeccions respiratòries, Global Health, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Respiratory Syncytial Viruses, Hospitalization, Risk Factors, Child, Preschool, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Hospital Mortality, Developing Countries, Respiratory Tract Infections
Abstract

BACKGROUND: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015. METHODS: We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity. FINDINGS: We estimated that globally in 2015, 33.1 million (uncertainty range [UR] 21.6-50.3) episodes of RSV-ALRI, resulted in about 3.2 million (2.7-3.8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1.4 million (UR 1.2-1.7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population. INTERPRETATION: Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group. FUNDING: The Bill & Melinda Gates Foundation.

Published
2017
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