Abstract
Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can suffer from severe coronavirus disease 2019 (COVID-19). However, compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit and death can be important. More details on the mechanism of action of SARS-CoV-2 could be defined. Moreover, the role played by children in virus diffusion should be better analyzed, and the development of effective preventive and therapeutic measures against COVID-19 could be favored. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults. Literature analysis showed that although most children are clearly protected from the development of severe COVID-19, the reasons for this peculiarity are not fully understood. Developmental variations in immune system function together with the potential role of repeated antigen stimulation in the first periods of life on innate immunity are widely studied. As the few children who develop the most severe form of pediatric COVID-19 have certain alterations in the immune system response to SARS-CoV-2 infection, studies about the relationships between SARS-CoV-2 and the immune system of the host are essential to understand the reasons for the age-related differences in the severity of COVID-19.
Highlights
Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)can suffer from severe coronavirus disease 2019 (COVID-19), as clearly shown by the reported cases of multisystem inflammatory syndrome in children (MIS-C) [1]
RNA viruses are recognized and bound by pattern recognition receptors (PRRs), such as toll-like receptor (TLR)-3 and TLR-7, which are expressed on the endoplasmic reticulum membrane of macrophages, dendritic cells and B lymphocytes, and by RIG-I and MDA5, which are located in the cytoplasm
Healthy children have a greater number of natural killer (NK) cells than adults and the elderly [33], which could explain the better response of children to SARS-CoV-2 infection, the ability of NK cells to produce cytokines does not exclude that they may play a role as pathogenic factors
Summary
Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). can suffer from severe coronavirus disease 2019 (COVID-19), as clearly shown by the reported cases of multisystem inflammatory syndrome in children (MIS-C) [1]. Children infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Can suffer from severe coronavirus disease 2019 (COVID-19), as clearly shown by the reported cases of multisystem inflammatory syndrome in children (MIS-C) [1]. Compared to adults and the elderly, susceptibility to SARS-CoV-2 infection in children seems to be lower; when infection does develop, most infected children remain asymptomatic or develop a mild disease [2]. Microorganisms 2021, 9, 330 individuals and hospitalized patients almost completely excluded asymptomatic children, there is no doubt that the risk of severe COVID-19 increases with age. Understanding why children seem generally protected from severe COVID-19 and only rarely develop clinical conditions that can cause hospitalization, admission to the pediatric intensive care unit (PICU) and death can be important. The main aim of this paper is to discuss the present knowledge on immunological and molecular mechanisms that could explain differences in COVID-19 clinical manifestations between children and adults
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