SARS-CoV-2 infections in children: Understanding diverse outcomes

Abstract

SARS-CoV-2 infections mostly lead to mild or even asymptomatic infections in children, but the reasons for this are not fully understood. More efficient local tissue responses, better thymic function, and cross-reactive immunity have all been proposed to explain this. In rare cases of children and young people, but very rarely in adults, post-infectious hyperinflammatory syndromes can develop and be serious. Here, I will discuss our current understanding of SARS-CoV-2 infections in children and hypothesize that a life history and energy allocation perspective might offer an additional explanation to mild infections, viral dynamics, and the higher incidence of rare multisystem inflammatory syndromes in children and young people.

Figure 1

Immune responses in mild and severe COVID-19 Characteristic differences between patients developing mild versus severe COVID-19 disease with delayed and imbalanced IFN-I responses, lymphopenia, and uncontrolled viral replication. Typical signs of mild versus severe COVID-19 in terms of cytokine production, inflammasome activation, and coagulopathy, as seen a number of population studies (Carvalho et al., 2021).

Figure 2

Viral dynamics in the young and old Relative viral load (arbitrary units, a.u.) over time (days from diagnosis) as determined by PCR from either nasopharyngeal or stool samples. A schematic model summarizing the results of multiple studies showing prolonged shedding of viral nucleic acid from stool, particularly in children.

Figure 3

An energy allocation theory to explain mild COVID-19 and MIS-C in children based on disease tolerance and viral persistence (A) Energy requirement (kcal/kg) decrease with age in US children and is slightly higher in boys than girls (adapted from Torun, 2005). The fraction of asymptomatic children among SARS-CoV-2 PCR+ children across the indicated age groups (Leidman et al., 2021), MIS-C incidence in the US per 100,000 children across indicated age groups (Belay et al., 2021), and MIS-C incidence per 1 million cases of COVID-19 across the indicated age groups (Payne et al., 2021). (B) In growing children, the threshold for energy-expenditure on system inflammatory responses are higher, leading to disease tolerance in most cases and mild to asymptomatic COVID-19, while in the elderly, the obese, and individuals with inadequate type-I IFN-respones, systemic inflammation is triggered, driving bystander T cell activation and immunopathology.