Hide and seek in a pandemic: review of SARS-CoV-2 infection and sequelae in children

Abstract

New findings: What is the topic of this review? A description of the current literature relating to COVID-19 infection in children and the associated inflammatory condition, paediatric multi-inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS). What advances does it highlight? Children with SARS-CoV-2 infection have a distinct clinical phenotype when compared to adults. This may relate to relative differences in their adaptive immunity and in the degree and distribution of expression of the SARS-CoV-2 receptor (angiotensin-converting enzyme 2). There are several similarities between PIMS-TS, Kawasaki disease shock syndrome and other known inflammatory disorders such as macrophage activation syndrome. Few data are available to date regarding vaccination responses of children against COVID-19.

Abstract: Children infected with SARS-CoV-2 have a clinical phenotype that is distinct from that observed in adult cases. They can present with a range of respiratory, gastrointestinal and neurological symptoms, or with a delayed hyperinflammatory syndrome (paediatric multisystem inflammatory system temporally associated with SARS-CoV-2; PIMS-TS) that frequently requires treatment in an intensive care unit. These manifestations may be related to unique expression of transmembrane receptors and immune physiology in children. The clinical features and inflammatory profile of PIMS-TS are similar to other inflammatory disorders that occur in children such as Kawasaki disease, macrophage activation syndrome and sepsis. Given children are infected less frequently and have less severe disease due to COVID-19 compared to adults, their physiological profile is of great interest. An understanding of the unique mechanisms of infection and disease in children could aid the identification of potential therapeutic targets. Like adults, children can have long-term complications of SARS-CoV-2 infection, including neurological and cardiac morbidity. Vaccination against SARS-CoV-2 is not yet authorised in children aged <12 years, and hence we anticipate ongoing paediatric presentations of COVID-19 in the coming months.

Keywords: COVID-19; COVID-19 related; paediatric multisystem inflammatory disease; pediatrics.

FIGURE 1

RCPCH case definition of PIMS‐TS

FIGURE 2

Profiles (Tang et al., 2008) of inflammatory (Lang et al., 2021) diseases in children (adapted from Canna & Behrens, 2012). BNP, brain natriuretic peptide; CSF, colony stimulating factor; ESR, eosinophil sedimentation rate; IFN, interferon; IL, interleukin; LDH, lactate dehydrogenase; M‐CSF, macrophage colony stimulating factor; MCP, monocyte chemoattractant protein; PIMS‐TS, paediatric multi‐inflammatory syndrome temporally associated with SARS‐CoV‐2; RA, receptor antagonist; TNF, tumour necrosis factor; −, decreased; +, increased; ++, significantly increased