In earlier epidemiologic examinations conducted on children with acute infection of COVID-19, was observed that the disease in children is mostly mild. It is crucial to comprehend the pathogenesis of COVID-19 in children by investigating its natural history in this age group. Two aspects were tackled in the immunopathogenesis of the disease in children. First of which is the inflammatory markers that are low in children as compared to adults. The other point was the change of angiotensin-converting enzyme 2 (ACE2) used by SARS-CoV-2 as the receptor cells for them in the human body. Children are known to have a low amount of those, which could contribute to mild disease in them. However, some contradicting studies on animals had shown that ACE2 protects against SARS-CoV-2, and it subsides with age.
Studies on adult COVID-19 patients have shown that severe outcomes are related to T-cell lymphopenia and cytokine storm. Antibody-dependent enhancement (ADE) is arbitrated by existing antibodies and B-cells. Spike protein has a minor level of homology with human coronaviruses (HCoVs). However, with other viral proteins, a higher homology in humans with more antibody titers and B-cells could result in complexes with SARS-CoV-2. ADE is a phenomenon in which binding a virus to suboptimal antibodies enhances its entry into host cells. Recent studies demonstrated that titers of HCoVs antibodies in adults are higher than in young adults, and those anti-HCoV are prone to cross with SARS-CoV-2.
This finding endorses the hypothesis that severe disease risk is far less in children with fewer antibodies. On the other hand, babies who have maternal antibodies in their bodies are more at risk of acquiring severe disease than kids older than that. Another crucial mechanism is that viruses work against other similar viruses. Thus, if children have other respiratory viruses, they prevent the development of SARS-CoV-2.