International Pediatric COVID-19 Severity Over the Course of the Pandemic
Authors: Zhu Yanshan , Almeida Flávia Jacqueline , Baillie J. Kenneth , Bowen Asha C. , Britton Philip N. , Brizuela Martin Eduardo , Buonsenso Danilo , Burgner David , Chew Keng Yih , Chokephaibulkit Kulkanya , Cohen Cheryl , Cormier Stephania A. , Crawford Nigel , Curtis Nigel , Farias Camila G. A. , Gilks Charles F. , von Gottberg Anne , Hamer Diana , Jarovsky Daniel , Jassat Waasila , Jesus Ana Rita , Kemp Lisa S. , Khumcha Benjawan , McCallum Georgina , Miller Jessica E. , Morello Rosa , Munro Alasdair P. S. , Openshaw Peter J. M. , Padmanabhan Srivatsan , Phongsamart Wanatpreeya , Reubenson Gary , Ritz Nicole , Rodrigues Fernanda , Rungmaitree Supattra , Russell Fiona , Sáfadi Marco A. P. , Saner Christoph , Semple Malcolm G. , Prado da Silva Daniella Gregória Bomfim , de Sousa Laíse Marine Moura , Diogo Moço Souza Marília , Spann Kirsten , Walaza Sibongile , Wolter Nicole , Xia Yao , Yeoh Daniel K. , Zar Heather J. , Zimmermann Petra , Short Kirsty R. ,   International Severe Acute Respiratory and Emerging Infection Consortium Comprehensive Clinical Characterisation Collaboration (ISARIC4C) investigatorsPediatric Active Enhanced Disease Surveillance (PAEDS) Network group, Alex Beatrice , Andrikopoulos Petros , Bach Benjamin , Barclay Wendy S , Bogaert Debby , Chand Meera , Chechi Kanta , Cooke Graham S , da Silva Filipe Ana , de Silva Thushan , Docherty Annemarie B , dos Santos Correia Gonçalo , Dumas Marc-Emmanuel , Dunning Jake , Fletcher Tom , Green Christopher A , Greenhalf William , Griffin Julian , Gupta Rishi K , Harrison Ewen M , Ho Antonia YW , Holden Karl , Horby Peter W , Ijaz Samreen , Khoo Say , Klenerman Paul , Law Andrew , Lewis Matthew , Liggi Sonia , Lim Wei Shen , Maslen Lynn , Mentzer Alexander J , Merson Laura , Meynert Alison M , Moore Shona C , Noursadeghi Mahdad , Olanipekun Michael , Osagie Anthonia , Palmarini Massimo , Palmieri Carlo , Paxton William A , Pollakis Georgios , Price Nicholas , Rambaut Andrew , Robertson David L , Russell Clark D , Sancho-Shimizu Vanessa , Sands Caroline , Scott Janet T , Sigfrid Louise , Solomon Tom , Sriskandan Shiranee , Stuart David , Summers Charlotte , Swann Olivia V , Takats Zoltan , Takis Panteleimon , Tedder Richard S , Thompson AA Roger , Thomson Emma C , Thwaites Ryan S , Turtle Lance CW , Zambon Maria , Drake Thomas M , Fairfield Cameron J , Knight Stephen R , Mclean Kenneth A , Murphy Derek , Norman Lisa , Pius Riinu , Shaw Catherine A , Connor Marie , Dalton Jo , Gamble Carrol , Girvan Michelle , Halpin Sophie , Harrison Janet , Jackson Clare , Lee James , Marsh Laura , Plotkin Daniel , Roberts Stephanie , Saviciute Egle , Clohisey Sara , Hendry Ross , Knight Susan , Lahnsteiner Eva , Leeming Gary , Norris Lucy , Scott-Brown James , Tait Sarah , Wham Murray , Clark Richard , Coutts Audrey , Donelly Lorna , Fawkes Angie , Gilchrist Tammy , Hafezi Katarzyna , MacGillivray Louise , Maclean Alan , McCafferty Sarah , Morrice Kirstie , Murphy Lee , Wrobel Nicola , Carson Gail , Adeniji Kayode , Agranoff Daniel , Agwuh Ken , Ail Dhiraj , Aldera Erin L. , Alegria Ana , Allen Sam , Angus Brian , Ashish Abdul , Atkinson Dougal , Bari Shahedal , Barlow Gavin , Barnass Stella , Barrett Nicholas , Bassford Christopher , Basude Sneha , Baxter David , Beadsworth Michael , Bernatoniene Jolanta , Berridge John , Berry Colin , Best Nicola , Bothma Pieter , Brittain-Long Robin , Bulteel Naomi , Burden Tom , Burtenshaw Andrew , Caruth Vikki , Chadwick David , Chambler Duncan , Chee Nigel , Child Jenny , Chukkambotla Srikanth , Clark Tom , Collini Paul , Cosgrove Catherine , Cupitt Jason , Cutino-Moguel Maria-Teresa , Dark Paul , Dawson Chris , Dervisevic Samir , Donnison Phil , Douthwaite Sam , Drummond Andrew , DuRand Ingrid , Dushianthan Ahilanadan , Dyer Tristan , Evans Cariad , Eziefula Chi , Fegan Chrisopher , Finn Adam , Fullerton Duncan , Garg Sanjeev , Garg Atul , Gkrania-Klotsas Effrossyni , Godden Jo , Goldsmith Arthur , Graham Clive , Grammatikopoulos Tassos , Hardy Elaine , Hartshorn Stuart , Harvey Daniel , Havalda Peter , Hawcutt Daniel B , Hobrok Maria , Hodgson Luke , Hormis Anil , Howard Joanne , Jacobs Michael , Jain Susan , Jennings Paul , Kaliappan Agilan , Kasipandian Vidya , Kegg Stephen , Kelsey Michael , Kendall Jason , Kerrison Caroline , Kerslake Ian , Koch Oliver , Koduri Gouri , Koshy George , Laha Shondipon , Laird Steven , Larkin Susan , Leiner Tamas , Lillie Patrick , Limb James , Linnett Vanessa , Little Jeff , Lyttle Mark , MacMahon Michael , MacNaughton Emily , Mankregod Ravish , Masson Huw , Matovu Elijah , McCullough Katherine , McEwen Ruth , Meda Manjula , Mills Gary , Minton Jane , Mohandas Kavya , Mok Quen , Moon James , Moore Elinoor , Morgan Patrick , Morris Craig , Mortimore Katherine , Moses Samuel , Mpenge Mbiye , Mulla Rohinton , Murphy Michael , Nagarajan Thapas , Nagel Megan , Nelson Mark , Norris Lillian , O'Shea Matthew K. , Ostermann Marlies , Otahal Igor , Pais Mark , Panchatsharam Selva , Papakonstantinou Danai , Papineni Padmasayee , Paraiso Hassan , Patel Brij , Pattison Natalie , Pepperell Justin , Peters Mark , Phull Mandeep , Pintus Stefania , Planche Tim , Post Frank , Price David , Prout Rachel , Rae Nikolas , Reschreiter Henrik , Reynolds Tim , Richardson Neil , Roberts Mark , Roberts Devender , Rose Alistair , Rousseau Guy , Ruge Bobby , Ryan Brendan , Saluja Taranprit , Sarah Sarah , Schmid Matthias , Shah Aarti , Shankar-Hari Manu , Shanmuga Prad , Sharma Anil , Shawcross Anna , Singh Pooni Jagtur , Sizer Jeremy , Smith Richard , Snelson Catherine , Spittle Nick , Staines Nikki , Stambach Tom , Stewart Richard , Subudhi Pradeep , Szakmany Tamas , Tatham Kate , Thomas Jo , Thompson Chris , Thompson Robert , Tridente Ascanio , Tupper-Carey Darell , Twagira Mary , Vallotton Nick , Vancheeswaran Rama , Vincent Rachel , Vincent-Smith Lisa , Visuvanathan Shico , Vuylsteke Alan , Waddy Sam , Wake Rachel , Walden Andrew , Welters Ingeborg , Whitehouse Tony , Whittaker Paul , Whittington Ashley , Wijesinghe Meme , Williams Martin , Wilson Lawrence , Winchester Stephen , Wiselka Martin , Wolverson Adam , Wootton Daniel G , Workman Andrew , Yates Bryan , Young Peter , McDonald Sarah E , Shaw Victoria , Ahmed Katie A. , Armstrong Jane A , Ashworth Milton , Asiimwe Innocent G , Bakshi Siddharth , Barlow Samantha L , Booth Laura , Brennan Benjamin , Bullock Katie , Carlucci Nicola , Cass Emily , Catterall Benjamin WA , Clark Jordan J , Clarke Emily A , Cole Sarah , Cooper Louise , Cox Helen , Davis Christopher , Dincarslan Oslem , Doce Carracedo Alejandra , Dunn Chris , Dyer Philip , Elliott Angela , Evans Anthony , Finch Lorna , Fisher Lewis WS , Flaherty Lisa , Foster Terry , Garcia-Dorival Isabel , Gunning Philip , Hartley Catherine , Holmes Anthony , Jensen Rebecca L , Jones Christopher B , Jones Trevor R , Khandaker Shadia , King Katharine , Kiy Robyn T. , Koukorava Chrysa , Lake Annette , Lant Suzannah , Latawiec Diane , Lavelle-Langham Lara , Lefteri Daniella , Lett Lauren , Livoti Lucia A , Mancini Maria , Massey Hannah , Maziere Nicole , McDonald Sarah , McEvoy Laurence , McLauchlan John , Metelmann Soeren , Miah Nahida S , Middleton Joanna , Mitchell Joyce , Murphy Ellen G , Penrice-Randal Rebekah , Pilgrim Jack , Prince Tessa , Reynolds Will , Ridley P. Matthew , Sales Debby , Shaw Victoria E , Shears Rebecca K , Small Benjamin , Subramaniam Krishanthi S , Szemiel Agnieska , Taggart Aislynn , Tanianis-Hughes Jolanta , Thomas Jordan , Trochu Erwan , van Tonder Libby , Wilcock Eve , Zhang J. Eunice , Keating Seán , Donegan Cara , Spencer Rebecca G , Donohue Chloe , Griffiths Fiona , Hardwick Hayley , Oosthuyzen Wilna , Glover Catherine , Carr Jeremy , Clark Julia , Marshall Helen , McMullan Brendan , Francis Joshua R. , Blyth Christopher C. , Macartney Kristine , Carey Emma , Wood Nicholas , Buttery Jim , Vasilunas Nan , Elliott Elizabeth , Richmond Peter , Wadia Ushma , McMinn Alissa , Bellamy Karen , Hunter Guillian , Meredith Kathryn , Rost Laura , Kerly Nicole , Dougherty Sonia , Cook Sara , Doran Natasha , Francis Laura , Heath Christine , Finucane Carolyn 
Published: August 2023

ImportanceMultiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear.ObjectiveTo determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children.Design, Setting, and ParticipantsClinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded.ExposuresSARS-CoV-2 hospitalization during the stipulated time frame.Main Outcomes and MeasuresThe severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy.ResultsAmong 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children.Conclusions and RelevanceThis study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.