Importance of understanding the reinfection risk of COVID-19 in children

Abstract

The Article by Anna A Mensah and colleagues1Mensah AA Campbell H Stowe J et al.Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England.Lancet Child Adolesc Health. 2022; (published online March 28.)https://doi.org/10.1016/S2352-4642(22)00059-1Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar addresses the important question of COVID-19 in children and the risk of reinfection over time in England. These data were collected before the emergence of the omicron variant of concern in England, but provide helpful insights into the overall picture of COVID-19, which has been quite different in children when compared with adults. Notably, with every decade of life there is an increasing risk of severe disease, including admission to hospital and death.This study also reinforces that the SARS-CoV-2 infection incidence in children is reflective of the trends observed in the community. The authors concluded that the risk of SARS-CoV-2 reinfection was strongly related to exposure due to community infection rates (particularly during the delta variant wave). They also noted that children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes.Children live with families or guardians and their school attendance and engagement in social networks are crucial to their development. The indirect effects of the pandemic on children, including the impact of COVID-19 on household family members, schooling, and mental health, are important to note.2Goldfeld S O'Connor E Sung V et al.Potential indirect impacts of the COVID-19 pandemic on children: a narrative review using a community child health lens.Med J Aust. 2022; (published online Jan 24.)https://doi.org/10.5694/mja2.51368Crossref PubMed Scopus (9) Google Scholar Hence, understanding the risk of reinfection in children is paramount, including the study finding that the reinfection rate was lowest in those not yet able to access a vaccine in most countries (ie, those younger than age 5 years). The lowest reinfection rate of 0·9 per 100 000 population was found in children younger than age 5 years, compared with 1·9 per 100 000 population in those aged 5–11 years and 5·5 per 100 000 population in those aged 12–16 years. These rates were 23, 11, and four times lower than in adults aged 20–29 years, who were unvaccinated and had the highest reinfection rate during that time period.The methodology used in the study establishes a framework to review the effect of vaccines on reinfection by age groups, noting that countries such as Australia, Canada, and the USA have all commenced an mRNA vaccination programme in children aged 5–11 years, as have the UK as per advice from the Joint Committee on Vaccination and Immunisation (JCVI) on Feb 16, 2022.3Department of Health and Social CareJCVI statement on vaccination of children aged 5 to 11 years old.https://www.gov.uk/government/publications/jcvi-update-on-advice-for-covid-19-vaccination-of-children-aged-5-to-11/jcvi-statement-on-vaccination-of-children-aged-5-to-11-years-oldDate: 2022Date accessed: March 22, 2022Google Scholar The JCVI recommendation is for children aged 5–11 years who have a clinical risk condition or are living wth someone who is immunosuporessed.A limitation of this paper was that it did not capture the impact of reinfection on paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, also known as multisystem inflammatory syndrome in children (MIS-C). This condition is a post inflammatory complication, occurring in children with a median age of 9 year and presenting about 2–6 weeks after SARS-CoV-2 infection.4Singh-Grewal D Lucas R McCarthy K et al.Update on the COVID-19-associated inflammatory syndrome in children and adolescents; paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2.J Paediatr Child Health. 2020; (published online July 31.)https://doi.org/10.1111/jpc.15049Crossref Scopus (25) Google Scholar A single COVID-19 vaccine dose has reduced the number of MIS-C cases according to publications from France and the USA, and further study is required to investigate if this complication also occurs after reinfection.5Zambrano LD Newhams MM Olson SM et al.Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12–18 years—United States, July–December 2021.MMWR Morb Mortal Wkly Rep. 2022; 71: 52-58Crossref PubMed Google Scholar, 6Levy M Recher M Hubert H et al.Multisystem inflammatory syndrome in children by COVID-19 vaccination status of adolescents in France.JAMA. 2022; 327: 281-283Crossref PubMed Scopus (42) Google ScholarThe study's finding that reinfection might not have been the reason for hospital admission (ie, patients might have been admitted to hospital with COVID-19, not because of COVID-19) is not unexpected. The medical history of paediatric readmission cases requires a detailed review of underlying co-morbidities and the final ICD-10 diagnoses. However, severe symptoms with COVID-19 are more common in those with a past medical history; in the study, the four children who had been admitted to an intensive care unit (ICU) following reinfection had also required intensive care during their primary infection. All four children had multiple and severe multisystem comorbidities and the authors could not ascertain the contribution of SARS-CoV-2 infection to the illness that eventually led to ICU admission. A publication by Ward and colleagues found that in the first year of the pandemic (2020), 51 children and adolescents in the UK were admitted to a paediatric ICU with COVID-19, and 91% of these children or adolescents had a pre-existing health condition.7Ward JL Harwood R Smith C et al.Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year.Nat Med. 2022; 28: 193-200Crossref PubMed Scopus (20) Google Scholar However, an important key finding of Mensah and colleagues' study is that reinfection with SARS-CoV-2 was not associated with fatal paediatric cases.1Mensah AA Campbell H Stowe J et al.Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England.Lancet Child Adolesc Health. 2022; (published online March 28.)https://doi.org/10.1016/S2352-4642(22)00059-1Summary Full Text Full Text PDF PubMed Scopus (10) Google ScholarA potential area for future research is the role that rapid antigen testing might play in identifying cases of reinfection, especially as many countries have introduced routine screening (eg, in schools). Many of these reinfection cases will be asymptomatic, so their role in transmission at household, school, and community levels will be important to monitor, particularly if new variants of concern emerge.Finally, investigation of the role that multiple reinfections will have on the immune system in vaccinated individuals will be important, with a particular focus on the development of B cell and T cell immune memory.8Crotty S Hybrid immunity.Science. 2021; 372: 1392-1393Crossref Scopus (89) Google Scholar The interplay between infection and vaccine will be crucial throughout 2022 and 2023 and will hopefully optimise protection across the life course and minimise the risk of reinfection (particularly that associated with severe disease), hospital admission, intensive care, and death. The Article by Anna A Mensah and colleagues1Mensah AA Campbell H Stowe J et al.Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England.Lancet Child Adolesc Health. 2022; (published online March 28.)https://doi.org/10.1016/S2352-4642(22)00059-1Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar addresses the important question of COVID-19 in children and the risk of reinfection over time in England. These data were collected before the emergence of the omicron variant of concern in England, but provide helpful insights into the overall picture of COVID-19, which has been quite different in children when compared with adults. Notably, with every decade of life there is an increasing risk of severe disease, including admission to hospital and death. This study also reinforces that the SARS-CoV-2 infection incidence in children is reflective of the trends observed in the community. The authors concluded that the risk of SARS-CoV-2 reinfection was strongly related to exposure due to community infection rates (particularly during the delta variant wave). They also noted that children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes. Children live with families or guardians and their school attendance and engagement in social networks are crucial to their development. The indirect effects of the pandemic on children, including the impact of COVID-19 on household family members, schooling, and mental health, are important to note.2Goldfeld S O'Connor E Sung V et al.Potential indirect impacts of the COVID-19 pandemic on children: a narrative review using a community child health lens.Med J Aust. 2022; (published online Jan 24.)https://doi.org/10.5694/mja2.51368Crossref PubMed Scopus (9) Google Scholar Hence, understanding the risk of reinfection in children is paramount, including the study finding that the reinfection rate was lowest in those not yet able to access a vaccine in most countries (ie, those younger than age 5 years). The lowest reinfection rate of 0·9 per 100 000 population was found in children younger than age 5 years, compared with 1·9 per 100 000 population in those aged 5–11 years and 5·5 per 100 000 population in those aged 12–16 years. These rates were 23, 11, and four times lower than in adults aged 20–29 years, who were unvaccinated and had the highest reinfection rate during that time period. The methodology used in the study establishes a framework to review the effect of vaccines on reinfection by age groups, noting that countries such as Australia, Canada, and the USA have all commenced an mRNA vaccination programme in children aged 5–11 years, as have the UK as per advice from the Joint Committee on Vaccination and Immunisation (JCVI) on Feb 16, 2022.3Department of Health and Social CareJCVI statement on vaccination of children aged 5 to 11 years old.https://www.gov.uk/government/publications/jcvi-update-on-advice-for-covid-19-vaccination-of-children-aged-5-to-11/jcvi-statement-on-vaccination-of-children-aged-5-to-11-years-oldDate: 2022Date accessed: March 22, 2022Google Scholar The JCVI recommendation is for children aged 5–11 years who have a clinical risk condition or are living wth someone who is immunosuporessed. A limitation of this paper was that it did not capture the impact of reinfection on paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2, also known as multisystem inflammatory syndrome in children (MIS-C). This condition is a post inflammatory complication, occurring in children with a median age of 9 year and presenting about 2–6 weeks after SARS-CoV-2 infection.4Singh-Grewal D Lucas R McCarthy K et al.Update on the COVID-19-associated inflammatory syndrome in children and adolescents; paediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2.J Paediatr Child Health. 2020; (published online July 31.)https://doi.org/10.1111/jpc.15049Crossref Scopus (25) Google Scholar A single COVID-19 vaccine dose has reduced the number of MIS-C cases according to publications from France and the USA, and further study is required to investigate if this complication also occurs after reinfection.5Zambrano LD Newhams MM Olson SM et al.Effectiveness of BNT162b2 (Pfizer-BioNTech) mRNA vaccination against multisystem inflammatory syndrome in children among persons aged 12–18 years—United States, July–December 2021.MMWR Morb Mortal Wkly Rep. 2022; 71: 52-58Crossref PubMed Google Scholar, 6Levy M Recher M Hubert H et al.Multisystem inflammatory syndrome in children by COVID-19 vaccination status of adolescents in France.JAMA. 2022; 327: 281-283Crossref PubMed Scopus (42) Google Scholar The study's finding that reinfection might not have been the reason for hospital admission (ie, patients might have been admitted to hospital with COVID-19, not because of COVID-19) is not unexpected. The medical history of paediatric readmission cases requires a detailed review of underlying co-morbidities and the final ICD-10 diagnoses. However, severe symptoms with COVID-19 are more common in those with a past medical history; in the study, the four children who had been admitted to an intensive care unit (ICU) following reinfection had also required intensive care during their primary infection. All four children had multiple and severe multisystem comorbidities and the authors could not ascertain the contribution of SARS-CoV-2 infection to the illness that eventually led to ICU admission. A publication by Ward and colleagues found that in the first year of the pandemic (2020), 51 children and adolescents in the UK were admitted to a paediatric ICU with COVID-19, and 91% of these children or adolescents had a pre-existing health condition.7Ward JL Harwood R Smith C et al.Risk factors for PICU admission and death among children and young people hospitalized with COVID-19 and PIMS-TS in England during the first pandemic year.Nat Med. 2022; 28: 193-200Crossref PubMed Scopus (20) Google Scholar However, an important key finding of Mensah and colleagues' study is that reinfection with SARS-CoV-2 was not associated with fatal paediatric cases.1Mensah AA Campbell H Stowe J et al.Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in England.Lancet Child Adolesc Health. 2022; (published online March 28.)https://doi.org/10.1016/S2352-4642(22)00059-1Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar A potential area for future research is the role that rapid antigen testing might play in identifying cases of reinfection, especially as many countries have introduced routine screening (eg, in schools). Many of these reinfection cases will be asymptomatic, so their role in transmission at household, school, and community levels will be important to monitor, particularly if new variants of concern emerge. Finally, investigation of the role that multiple reinfections will have on the immune system in vaccinated individuals will be important, with a particular focus on the development of B cell and T cell immune memory.8Crotty S Hybrid immunity.Science. 2021; 372: 1392-1393Crossref Scopus (89) Google Scholar The interplay between infection and vaccine will be crucial throughout 2022 and 2023 and will hopefully optimise protection across the life course and minimise the risk of reinfection (particularly that associated with severe disease), hospital admission, intensive care, and death. I declare no competing interests. Risk of SARS-CoV-2 reinfections in children: a prospective national surveillance study between January, 2020, and July, 2021, in EnglandThe risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes. Full-Text PDF Open Access