Immune response to SARS-CoV-2 in children: A review of the current knowledge

Abstract

Host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in children, are still under investigation. Children with coronavirus disease 2019 (COVID-19) constitute a significant study group of immune responses as they rarely present with severe clinical manifestations, require hospitalization, or develop complications such as multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. The deciphering of children's immune responses during COVID-19 infection will provide information about the protective mechanisms, while new potential targets for future therapies are likely to be revealed. Despite the limited immunological studies in children with COVID-19, this review compares data between adults and children in terms of innate and adaptive immunity to SARS-CoV-2, discusses the possible reasons why children are mostly asymptomatic, and highlights unanswered or unclear immunological issues. Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS-CoV-2 infection and adaptive memory immunity is vital to prevent reinfection.

Keywords: COVID‐19; Children; Immunity; Multisystem inflammatory syndrome; SARS‐CoV‐2.

FIGURE 1

Basic molecular mechanisms of innate immune cells in response to SARS‐CoV‐2 infection. (1) Cells of the innate immune recognize pathogen‐associated molecular patterns (PAMPs), like viral proteins and double‐stranded RNA (dsRNA), through transmembrane or intracellular pattern recognition receptors (PRRs) such as toll‐Like receptors (TLRs) or RIG‐I‐like receptors (RLRs) consisting of the retinoic acid‐inducible gene‐I (RIG‐I) and the melanoma differentiation‐associated protein 5 (MDA5). (2) This recognition leads to the activation of the transcription factors, nuclear factor kappa B (NF‐κB), interferon regulatory factor 3 (IRF3), and IRF7, resulting in the expression of interferons (IFNs) α/β. (3) The binding of INF‐α/β to interferon‐alpha/beta receptor (INFAR) activates the JAK/STAT signaling pathway, which leads to (4) the expression of interferon‐stimulated genes (ISGs), by the signal transducer and activator of transcription 1 (STAT1), STAT2 and IRF9, and (5) finally to release of different cytokines, chemokines and anti‐viral proteins. The figure was designed by the biorender in silico tool (https://app.biorender.com/).