Silence of the Lambs: The Immunological and Molecular Mechanisms of COVID-19 in Children in Comparison with Adults

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.

COVID-19 Management in the Pediatric Age: Consensus Document of the COVID-19 Working Group in Paediatrics of the Emilia-Romagna Region (RE-CO-Ped), Italy

“…Cardiac involvement manifestations may be an increase in enzymes (troponin and pro-BNP in 80.9% and 84.9% of cases, respectively) and/or left ventricular dysfunction (45%), valve failure (mitral and aortic), pericarditis and arrhythmias [82,83,[86][87][88][89][90][91][92]. Coronary dilations or aneurysms in the acute phase of the disease are documented in 6-24% of cases [82,83,[87][88][89][90][93][94][95][96][97][98][99][100][101]: they are generally of a non-severe degree and decline in most cases [102]. Given the systemic nature of the syndrome, mucocutaneous interest with rash, conjunctivitis and peripheral edema is also frequent [82,[103][104][105].…”

Can we get out of the COVID pandemic without adequate vaccination coverage in the pediatric population?

“…Omicron SARS-CoV-2 variant has increased transmissibility than the original SARS-CoV-2 [9] and it cannot be excluded that, despite children were less susceptible than adults to the original virus [10], they can be more easily infected by the new virus. Moreover, when Omicron appeared, a great number of adults and elderlies had a certain degree of protection against this virus as many of them had been already infected or vaccinated against SARS-CoV2.…”

Use of Monoclonal Antibody to Treat COVID-19 in Children and Adolescents: Risk of Abuse of Prescription and Exacerbation of Health Inequalities

“…A problem is that the authorization for mAb use in children was given without studies previously evaluating the efficacy, safety and tolerability of mAbs in pediatric patients. Moreover, although the total number of children with chronic severe underlying disease is not marginal, the risk of severe COVID-19 in pediatric age is significantly lower than in adults [ 14 , 15 ] and the role of a chronic underlying disease as a risk factor of severe COVID-19 development in pediatric patients is far from being precisely defined [ 16 ]. When infected, pediatric patients generally are asymptomatic or with mild disease.…”