Systematic review
Vol. 151 No. 3738 (2021)
The role of children and adolescents in the SARS-CoV-2 pandemic: a rapid review
- Margarethe Wiedenmann
- Myrofora Goutaki
- Olivia Keiser
- Silvia Stringhini
- Marcel Tanner
- Nicola Low
Summary
BACKGROUND: There has been much discussion about coronavirus disease 2019 (COVID-19) and the virus that causes it, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents, since the pandemic was recognised in early 2020. Understanding their role in this pandemic is important for the development of appropriate prevention measures.
OBJECTIVE: To summarise evidence about three aspects of SARS-CoV-2 and COVID-19 in children and adolescents: (1) severity of SARS-CoV-2 presentation, (2) risk of SARS-CoV-2 infection and (3) risk of transmitting SARS-CoV-2.
METHODS: We searched PubMed and MedRxiv for studies on SARS-CoV-2 and COVID-19 in children and adolescents from January 2020 to 21 January 2021. The electronic search was supplemented by papers found in a manual search or suggested by experts up to 29 March 2021. We included case reports, cross-sectional studies, cohort studies, narrative reviews or viewpoints, systematic reviews and modelling studies. We synthesised the information descriptively and attempted to report findings separately for: infants and small children (0–5 years) who are mostly pre-school; school children (6–12 years) broadly covering primary school years; and adolescents (13–17 years).
RESULTS: Of 2778 screened articles, we included 63 (20 case reports, 18 cross-sectional studies, 8 cohort studies, 6 narrative reviews or viewpoints, 10 systematic reviews and 1 modelling study). Children (≤12 years of age) and adolescents (13–17 years of age) usually present with mild disease, with few requiring intensive care treatment. A minority of children of all ages (<18 years) remains asymptomatic throughout the course of infection. In serological studies, reported symptoms are similar in children with and without SARS-CoV-2 antibodies. Children and adolescents can acquire and transmit SARS-CoV-2. The risks of acquiring and transmitting SARS-CoV-2 seems to increase with age. There was limited information about SARS-CoV-2 variants of concern. Poor reporting of age groups and contextual factors such as levels of community transmission, school closures and other non-pharmaceutical interventions make synthesis of findings across studies difficult.
CONCLUSIONS: The clinical presentation and role of children and adolescents in SARS-CoV-2 susceptibility and transmission needs further investigation, particularly with regard to variants of concern. Large, prospective studies that attempt to minimise biases in design, are analysed appropriately and reported comprehensively should be conducted.
References
- Boast A, Munro A, Goldstein H. An evidence summary of Paediatric COVID-19 literature. Don't Forget the Bubbles. 2020.
- Goldstein E, Lipsitch M, Cevik M. On the Effect of Age on the Transmission of SARS-CoV-2 in Households, Schools, and the Community. J Infect Dis. 2021 Feb;223(3):362–9. https://doi.org/10.1093/infdis/jiaa691
- Hyde Z. COVID-19, children and schools: overlooked and at risk. Med J Aust. 2020 Nov;213(10):444–446.e1. https://doi.org/10.5694/mja2.50823
- Van Lancker W, Parolin Z. COVID-19, school closures, and child poverty: a social crisis in the making. Lancet Public Health. 2020 May;5(5):e243–4. https://doi.org/10.1016/S2468-2667(20)30084-0
- Silverman M, Sibbald R, Stranges S. Ethics of COVID-19-related school closures. Can J Public Health. 2020 Aug;111(4):462–5. https://doi.org/10.17269/s41997-020-00396-1
- Morand A, Fabre A, Minodier P, Boutin A, Vanel N, Bosdure E, et al. COVID-19 virus and children: what do we know? Arch Pediatr. 2020 Apr;27(3):117–8. https://doi.org/10.1016/j.arcped.2020.03.001
- Accorsi EK, Qiu X, Rumpler E, Kennedy-Shaffer L, Kahn R, Joshi K, et al. How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19. Eur J Epidemiol. 2021 Feb;36(2):179–96. https://doi.org/10.1007/s10654-021-00727-7
- Swiss National COVID-19 Science Task Force. The role of children (≤12 years of age) and adolescents (13-17 years of age) in the SARS-CoV-2 pandemic: A rapid review. 2021.
- World Health Organization. COVID-19 Weekly Epidemiological Update. 2021;Edition 41.
- Liu W, Zhang Q, Chen J, Xiang R, Song H, Shu S, et al. Detection of Covid-19 in Children in Early January 2020 in Wuhan, China. N Engl J Med. 2020 Apr;382(14):1370–1. https://doi.org/10.1056/NEJMc2003717
- Mustafa NM, A Selim L. Characterisation of COVID-19 Pandemic in Paediatric Age Group: A Systematic Review and Meta-Analysis. J Clin Virol. 2020 Jul;128:104395. https://doi.org/10.1016/j.jcv.2020.104395
- Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al.; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 Infection in Children. N Engl J Med. 2020 Apr;382(17):1663–5. https://doi.org/10.1056/NEJMc2005073
- Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology of COVID-19 Among Children in China. Pediatrics. 2020 Jun;145(6):e20200702. https://doi.org/10.1542/peds.2020-0702
- Castagnoli R, Votto M, Licari A, Brambilla I, Bruno R, Perlini S, et al. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Children and Adolescents: A Systematic Review. JAMA Pediatr. 2020 Sep;174(9):882–9. https://doi.org/10.1001/jamapediatrics.2020.1467
- Hoang A, Chorath K, Moreira A, Evans M, Burmeister-Morton F, Burmeister F, et al. COVID-19 in 7780 pediatric patients: A systematic review. EClinicalMedicine. 2020 Jun;24:100433. https://doi.org/10.1016/j.eclinm.2020.100433
- Buitrago-Garcia D, Egli-Gany D, Counotte MJ, Hossmann S, Imeri H, Ipekci AM, et al. Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections: A living systematic review and meta-analysis. PLoS Med. 2020 Sep;17(9):e1003346. https://doi.org/10.1371/journal.pmed.1003346
- Richard A, Wisniak A, Perez-Saez J, Garrison-Desany H, Petrovic D, Piumatti G, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies, risk factors for infection and associated symptoms in Geneva, Switzerland: a population-based study. medRxiv. 2020.
- Ulyte A, Radtke T, Abela IA, Haile SR, Blankenberger J, Jung R, et al. Variation in SARS-CoV-2 seroprevalence across districts, schools and classes: baseline measurements from a cohort of primary and secondary school children in Switzerland. BMJ Open. 2021 Jul;11(7):e047483. https://doi.org/10.1136/bmjopen-2020-047483
- Ulyte A, Radtke T, Abela IA, Haile SR, Berger C, Huber M, et al. Clustering and longitudinal change in SARS-CoV-2 seroprevalence in school children in the canton of Zurich, Switzerland: prospective cohort study of 55 schools. BMJ. 2021 Mar;372(616):n616. https://doi.org/10.1136/bmj.n616
- Bialek S, Gierke R, Hughes M, McNamara LA, Pilishvili T, Skoff T ; CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children - United States, February 12-April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020 Apr;69(14):422–6. https://doi.org/10.15585/mmwr.mm6914e4
- Gordon M, Kagalwala T, Rezk K, Rawlingson C, Ahmed MI, Guleri A. Rapid systematic review of neonatal COVID-19 including a case of presumed vertical transmission. BMJ Paediatr Open. 2020 May;4(1):e000718. https://doi.org/10.1136/bmjpo-2020-000718
- Dumpa V, Kamity R, Vinci AN, Noyola E, Noor A. Neonatal Coronavirus 2019 (COVID-19) Infection: A Case Report and Review of Literature. Cureus. 2020 May;12(5):e8165.
- Sheth S, Shah N, Bhandari V. Outcomes in COVID-19 Positive Neonates and Possibility of Viral Vertical Transmission: A Narrative Review. Am J Perinatol. 2020 Oct;37(12):1208–16. https://doi.org/10.1055/s-0040-1714719
- Kyle MH, Glassman ME, Khan A, Fernández CR, Hanft E, Emeruwa UN, et al. A review of newborn outcomes during the COVID-19 pandemic. Semin Perinatol. 2020 Nov;44(7):151286. https://doi.org/10.1016/j.semperi.2020.151286
- Vardhelli V, Pandita A, Pillai A, Badatya SK. Perinatal COVID-19: review of current evidence and practical approach towards prevention and management. Eur J Pediatr. 2021 Apr;180(4):1009–31. https://doi.org/10.1007/s00431-020-03866-3
- Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China. JAMA. 2020 Apr;323(13):1313–4. https://doi.org/10.1001/jama.2020.2131
- Zhang ZJ, Yu XJ, Fu T, Liu Y, Jiang Y, Yang BX, et al. Novel coronavirus infection in newborn babies aged <28 days in China. Eur Respir J. 2020 Jun;55(6):2000697. https://doi.org/10.1183/13993003.00697-2020
- Gale C, Quigley MA, Placzek A, Knight M, Ladhani S, Draper ES, et al. Characteristics and outcomes of neonatal SARS-CoV-2 infection in the UK: a prospective national cohort study using active surveillance. Lancet Child Adolesc Health. 2021 Feb;5(2):113–21. https://doi.org/10.1016/S2352-4642(20)30342-4
- Swann OV, Holden KA, Turtle L, Pollock L, Fairfield CJ, Drake TM, et al.; ISARIC4C Investigators. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study. BMJ. 2020 Aug;370:m3249. https://doi.org/10.1136/bmj.m3249
- Balduzzi A, Brivio E, Rovelli A, Rizzari C, Gasperini S, Melzi ML, et al. Lessons after the early management of the COVID-19 outbreak in a pediatric transplant and hemato-oncology center embedded within a COVID-19 dedicated hospital in Lombardia, Italy. Estote parati. Bone Marrow Transplant. 2020 Oct;55(10):1900–5. https://doi.org/10.1038/s41409-020-0895-4
- Ferrari A, Zecca M, Rizzari C, Porta F, Provenzi M, Marinoni M, et al. Children with cancer in the time of COVID-19: An 8-week report from the six pediatric onco-hematology centers in Lombardia, Italy. Pediatr Blood Cancer. 2020 Aug;67(8):e28410. https://doi.org/10.1002/pbc.28410
- Marlais M, Wlodkowski T, Vivarelli M, Pape L, Tönshoff B, Schaefer F, et al. The severity of COVID-19 in children on immunosuppressive medication. Lancet Child Adolesc Health. 2020 Jul;4(7):e17–8. https://doi.org/10.1016/S2352-4642(20)30145-0
- Boulad F, Kamboj M, Bouvier N, Mauguen A, Kung AL. COVID-19 in Children With Cancer in New York City. JAMA Oncol. 2020 Sep;6(9):1459–60. https://doi.org/10.1001/jamaoncol.2020.2028
- Hrusak O, Kalina T, Wolf J, Balduzzi A, Provenzi M, Rizzari C, et al. Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment. Eur J Cancer. 2020 Jun;132:11–6. https://doi.org/10.1016/j.ejca.2020.03.021
- Minotti C, Tirelli F, Barbieri E, Giaquinto C, Donà D. How is immunosuppressive status affecting children and adults in SARS-CoV-2 infection? A systematic review. J Infect. 2020 Jul;81(1):e61–6. https://doi.org/10.1016/j.jinf.2020.04.026
- Rawson A, Wilson AC, Schwaderer AL, Spiwak E, Johnston B, Anderson S, et al. Coronavirus disease 2019 (COVID-19) in two pediatric patients with kidney disease on chronic immunosuppression: A case series. Hemodial Int. 2021 Jan;25(1):E1–5. https://doi.org/10.1111/hdi.12876
- Jones VG, Mills M, Suarez D, Hogan CA, Yeh D, Segal JB, et al. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case. Hosp Pediatr. 2020 Jun;10(6):537–40. https://doi.org/10.1542/hpeds.2020-0123
- Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020 May;395(10237):1607–8. https://doi.org/10.1016/S0140-6736(20)31094-1
- Dufort EM, Koumans EH, Chow EJ, Rosenthal EM, Muse A, Rowlands J, et al.; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. 2020 Jul;383(4):347–58. https://doi.org/10.1056/NEJMoa2021756
- Buonsenso D, Munblit D, De Rose C, Sinatti D, Ricchiuto A, Carfi A, et al. Preliminary evidence on long COVID in children. Acta Paediatr. 2021 Jul;110(7):2208–11. https://doi.org/10.1111/apa.15870
- Lavezzo E, Franchin E, Ciavarella C, Cuomo-Dannenburg G, Barzon L, Del Vecchio C, et al.; Imperial College COVID-19 Response Team; Imperial College COVID-19 Response Team. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature. 2020 Aug;584(7821):425–9. https://doi.org/10.1038/s41586-020-2488-1
- Children’s Task and Finish Group. Children’s Task and Finish Group : update to 4th Nov 2020 paper on children, schools and transmission. 2020.
- Viner RM, Mytton OT, Bonell C, Melendez-Torres GJ, Ward J, Hudson L, et al. Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis. JAMA Pediatr. 2021 Feb;175(2):143–56. https://doi.org/10.1001/jamapediatrics.2020.4573
- Zhu Y, Bloxham CJ, Hulme KD, Sinclair JE, Tong ZW, Steele LE, et al. A meta-analysis on the role of children in SARS-CoV-2 in household transmission clusters. Clin Infect Dis. 2020.
- Madewell ZJ, Yang Y, Longini IM Jr, Halloran ME, Dean NE. Household Transmission of SARS-CoV-2: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Dec;3(12):e2031756. https://doi.org/10.1001/jamanetworkopen.2020.31756
- Li W, Zhang B, Lu J, Liu S, Chang Z, Peng C, et al. Characteristics of Household Transmission of COVID-19. Clin Infect Dis. 2020 Nov;71(8):1943–6. https://doi.org/10.1093/cid/ciaa450
- Yung CF, Kam KQ, Chong CY, Nadua KD, Li J, Tan NW, et al. Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 from Adults to Children. J Pediatr. 2020 Oct;225:249–51. https://doi.org/10.1016/j.jpeds.2020.07.009
- Somekh E, Gleyzer A, Heller E, Lopian M, Kashani-Ligumski L, Czeiger S, et al. The Role of Children in the Dynamics of Intra Family Coronavirus 2019 Spread in Densely Populated Area. Pediatr Infect Dis J. 2020 Aug;39(8):e202–4. https://doi.org/10.1097/INF.0000000000002783
- Pollán M, Pérez-Gómez B, Pastor-Barriuso R, Oteo J, Hernán MA, Pérez-Olmeda M, et al.; ENE-COVID Study Group. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020 Aug;396(10250):535–44. https://doi.org/10.1016/S0140-6736(20)31483-5
- Stringhini S, Wisniak A, Piumatti G, Azman AS, Lauer SA, Baysson H, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet. 2020 Aug;396(10247):313–9. https://doi.org/10.1016/S0140-6736(20)31304-0
- Stringhini S, Zaballa ME, Perez-Saez J, Pullen N, de Mestral C, Picazio A, et al.; Specchio-COVID19 Study Group. Seroprevalence of anti-SARS-CoV-2 antibodies after the second pandemic peak. Lancet Infect Dis. 2021 May;21(5):600–1. https://doi.org/10.1016/S1473-3099(21)00054-2
- Debatin K-M, Henneke P, Hoffmann GF, Kräusslich H-G. Prevalence of COVID-19 in children in Baden-Württemberg - Preliminary study report. 2020.
- Torres JP, Pinera C, De La Maza V, Lagomarcino AJ, Simian D, Torres B, et al. SARS-CoV-2 antibody prevalence in blood in a large school community subject to a Covid-19 outbreak: a cross-sectional study. Clin Infect Dis. 2021;73(2):e458–65. https://doi.org/10.1093/cid/ciaa955
- L’Huillier AG, Torriani G, Pigny F, Kaiser L, Eckerle I. Culture-Competent SARS-CoV-2 in Nasopharynx of Symptomatic Neonates, Children, and Adolescents. Emerg Infect Dis. 2020 Oct;26(10):2494–7. https://doi.org/10.3201/eid2610.202403
- Baggio S, L’Huillier AG, Yerly S, Bellon M, Wagner N, Rohr M, et al. SARS-CoV-2 viral load in the upper respiratory tract of children and adults with early acute COVID-19. Clin Infect Dis. 2020.
- Jones TC, Mühlemann B, Veith T, Biele G, Zuchowski M, Hofmann J, et al. An analysis of SARS-CoV-2 viral load by patient age. medRxiv. 2020:2020.06.08.20125484. https://doi.org/10.1101/2020.06.08.20125484
- Held L. A discussion and reanalysis of the results reported in Jones et al. (2020). 2020.
- Fontanet A, Tondeur L, Madec Y, Grant R, Besombes C, Jolly N, et al. Cluster of COVID-19 in northern France: A retrospective closed cohort study. medRxiv. 2020:2020.04.18.20071134.
- Szablewski CM, Chang KT, Brown MM, Chu VT, Yousaf AR, Anyalechi N, et al. SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp - Georgia, June 2020. MMWR Morb Mortal Wkly Rep. 2020 Aug;69(31):1023–5. https://doi.org/10.15585/mmwr.mm6931e1
- Pray IW, Gibbons-Burgener SN, Rosenberg AZ, Cole D, Borenstein S, Bateman A, et al. COVID-19 Outbreak at an Overnight Summer School Retreat - Wisconsin, July-August 2020. MMWR Morb Mortal Wkly Rep. 2020 Oct;69(43):1600–4. https://doi.org/10.15585/mmwr.mm6943a4
- Stein-Zamir C, Abramson N, Shoob H, Libal E, Bitan M, Cardash T, et al. A large COVID-19 outbreak in a high school 10 days after schools’ reopening, Israel, May 2020. Euro Surveill. 2020 Jul;25(29). https://doi.org/10.2807/1560-7917.ES.2020.25.29.2001352
- Yung CF, Kam KQ, Nadua KD, Chong CY, Tan NW, Li J, et al. Novel Coronavirus 2019 Transmission Risk in Educational Settings. Clin Infect Dis. 2021 Mar;72(6):1055–8. https://doi.org/10.1093/cid/ciaa794
- The National Centre for Immunisation Research and Surveillance (NCIRS). COVID-19 in schools – the experience in NSW. 2020.
- Heavey L, Casey G, Kelly C, Kelly D, McDarby G. No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020. Euro Surveill. 2020 May;25(21). https://doi.org/10.2807/1560-7917.ES.2020.25.21.2000903
- Ehrhardt J, Ekinci A, Krehl H, Meincke M, Finci I, Klein J, et al. Transmission of SARS-CoV-2 in children aged 0 to 19 years in childcare facilities and schools after their reopening in May 2020, Baden-Württemberg, Germany. Euro Surveill. 2020 Sep;25(36). https://doi.org/10.2807/1560-7917.ES.2020.25.36.2001587
- Link-Gelles R, DellaGrotta AL, Molina C, Clyne A, Campagna K, Lanzieri TM, et al. Limited Secondary Transmission of SARS-CoV-2 in Child Care Programs - Rhode Island, June 1-July 31, 2020. MMWR Morb Mortal Wkly Rep. 2020 Aug;69(34):1170–2. https://doi.org/10.15585/mmwr.mm6934e2
- Yoon Y, Choi GJ, Kim JY, Kim KR, Park H, Chun JK, et al. Childcare Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 for 4-Year-Old Presymptomatic Child, South Korea. Emerg Infect Dis. 2021 Feb;27(2):341–7. https://doi.org/10.3201/eid2702.203189
- Ismail SA, Saliba V, Lopez Bernal J, Ramsay ME, Ladhani SN. SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England. Lancet Infect Dis. 2021 Mar;21(3):344–53. https://doi.org/10.1016/S1473-3099(20)30882-3
- Gold JA, Gettings JR, Kimball A, Franklin R, Rivera G, Morris E, et al.; Georgia K–12 School COVID-19 Investigation Team. Clusters of SARS-CoV-2 Infection Among Elementary School Educators and Students in One School District - Georgia, December 2020-January 2021. MMWR Morb Mortal Wkly Rep. 2021 Feb;70(8):289–92. https://doi.org/10.15585/mmwr.mm7008e4
- Volz E, Mishra S, Chand M, Barrett JC, Johnson R, Geidelberg L, et al. Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data. medRxiv. 2021:2020.12.30.20249034.
- Radtke T, Ulyte A, Puhan MA, Kriemler S. Long-term Symptoms After SARS-CoV-2 Infection in Children and Adolescents. JAMA. 2021 Jul. https://doi.org/10.1001/jama.2021.11880
- Molteni E, Sudre CH, Canas LS, Bhopal SS, Hughes RC, Antonelli M, et al. Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health. 2021 Aug;S2352-4642(21)00198-X.
- Loenenbach A, Markus I, Lehfeld AS, An der Heiden M, Haas W, Kiegele M, et al. SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021. Euro Surveill. 2021 May;26(21). https://doi.org/10.2807/1560-7917.ES.2021.26.21.2100433