Children Naturally Evading COVID-19—Why Children Differ from Adults

Abstract

Coronavirus Disease 2019 (COVID-19) has spread across the world, caused lockdowns, and has had serious economic and social consequences. COVID-19 manifests differently in children than adults, as children usually have a milder course of disease, mild symptoms if any, and lower fatality rates are recorded among children. SARS-CoV-2 transmission also seems to be different between children and adults. Many factors are proposed to explain the milder outcome in children, e.g., a more appropriate immune response (especially active innate response), trained immunity, a lack of immunosenescence, and the reduced prevalence of comorbidities. A better understanding of the differences in susceptibility and outcome in children compared with adults could lead to greater knowledge of risk factors for complicated COVID-19 cases and potential treatment targets. We highlight proposed reasons as to why children are less affected by COVID-19 than adults.

Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19

“…However, early induction of T lymphocytes that secrete IFNs targeting SARS-CoV-2 is associated with patients who exhibited milder symptoms and accelerated viral clearance [ 133 ]. The fact that the IFN innate immune signaling system in healthy children is primed and ready in a preactivated state across several epithelial cell types may also explain milder COVID-19 disease severity in children compared to adults as a result of increased timely responsiveness to viral attack [ 134 , 135 , 136 , 137 ]. In addition, type I IFNs and ISGs are poorly induced especially after the establishment of SARS-CoV-2 infection, but the blockade of IFN signaling can be largely impeded by IFN pretreatment (6 h preinfection) while post-infection treatment at 16 h yielded only modest results [ 138 ].…”

Nonspecific Effects of Infant Vaccines Make Children More Resistant to SARS-CoV-2 Infection

“…Franklin et al demonstrated that macrodomains of SARS-CoV-2 , the rubella virus, and its component in the PRS vaccine (Mumps, Rubella, and Measles) vaccine have a 29% amino acid identity [ 8 ]. This finding suggests that both viruses and the corresponding component in PRS share at least one protein fold.…”

“…In general, children pass through the most favorable end of the clinical spectrum mentioned in the previous paragraph. Unlike other infectious diseases, such as malaria and the common flu, in which children exhibit higher incidence and mortality rates than older people, SARS-CoV-2 infection among pediatric ages is less frequent and relatively benign, as it occurs with many childhood diseases, for example, herpesviruses (VZV and EBV), which tend to be worse when the first infection is in adulthood [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Similar behaviors were recorded on the occasion of infections caused by SARS-CoV and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) , the coronaviruses that caused two pandemics at the beginning of this century [ 10 , 11 ].…”

“…Among the protective factors present in pediatric ages, the following are mentioned as explanations: (i) Lower intensity of exposure to SARS-CoV-2 (since the family dynamics established during the pandemic are intended to protect the youngest) [ 13 ]; (ii) Higher steady-state expression of interferon (IFN) response genes in the airway epithelium of children, which can result in less viral spreading (however, if this factor was broadly significant, children should be more resistant to many respiratory viruses, but this is not the case because, for example, children are more sensitive to influenza A virus) [ 14 ]; (iii) Better functioning immune mechanisms, especially those of innate immunity (for example, better containment of infectious processes by natural antibodies) [ 3 ]; (iv) Higher frequency of recurrent and concurrent viral infections (these infections can induce a state of activation of the innate immune system, which includes the epigenetic changes that characterize the training of innate immunity) [ 15 , 16 ]; (v) Modulation of the inflammatory component of host immune responses to helminthic infections, which is more frequent among pediatric ages [ 17 ]; (vi) Gut microbiota changes with age, which potentially provide a better defense against infection (for instance, children generally have higher numbers of Bifidobacterium than adults) [ 18 ]. Children may also have a higher nasopharyngeal colonization of viruses and bacteria, which by competition may limit the growth of SARS-CoV-2 and lead to a reduced colonization of the pathogen [ 8 ].…”

Challenges in the Detection of SARS-CoV-2: Evolution of the Lateral Flow Immunoassay as a Valuable Tool for Viral Diagnosis

“…Whereas the pandemic started, LFIAs tests showed variable performance when assessing test sensitivity and specificity towards the main immunogenic structures of the virus. In pediatric age (2 months to 18 years), COVID-19 symptoms are generally less severe than in adults, and a low level of antibodies is produced [ 75 ]. This immune response is associated with a low yield of sensitivity of LFIA antibody detection (about 70%); this value was lower in the second week after disease onset.…”