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How Children Are Protected From COVID-19? A Historical, Clinical, and Pathophysiological Approach to Address COVID-19
Magdalena Anna Massalska1, Hans-Jürgen Gober2
1Department of Pathophysiology and Immunology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw, Poland.
Insights
Native IgM may protect children from severe COVID-19, unlike adults. This immune component, prevalent in the young, might recognize viral danger signals, potentially explaining lower pediatric mortality rates along the ancient Silk Road trade routes.
Area of Science:
- Immunology
- Virology
- Epidemiology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused high mortality in regions along the ancient Silk Road.
- Children and neonates exhibited significantly lower illness and mortality rates during the COVID-19 pandemic.
- This suggests a protective role for components of the early adaptive immune system.
Purpose of the Study:
- To investigate the potential protective role of native immunoglobulin M (IgM) in children against severe COVID-19.
- To explore the link between COVID-19, Behcet's disease, and genetic factors shaped by historical pathogen exposure along the Silk Road.
Main Methods:
- Review of clinical data and immunological literature concerning COVID-19, pediatric immunity, and Behcet's disease.
- Analysis of the proposed molecular mechanisms involving native IgM, viral envelope recognition, and reactive oxygen species.
Main Results:
- Native IgM, abundant in children, may neutralize SARS-CoV-2 by recognizing danger signals on infected cells.
- Shared symptoms like thrombosis and vasculitis in COVID-19 and Behcet's disease suggest a common pathway.
- Reactive oxygen species are implicated as triggers for severe COVID-19, linking it to innate immune responses against bacteria.
Conclusions:
- Native IgM is a potential factor in protecting children from severe COVID-19.
- Historical selective pressures from bacterial pathogens along the Silk Road may have conferred a genetic advantage against severe COVID-19 in descendant populations.
- Further research is warranted to elucidate the precise mechanisms of IgM-mediated protection and the role of genetic predisposition.
Abstract:
The origin and the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) in early 2020 was accompanied by high rates of mortality in regions belonging to the ancient silk road, such as the south of China, Iran, Turkey and the northern parts of Italy. However, children seem to be spared in the epidemic as very small percentage worldwide being ill. The protection of children and neonates suggests the involvement of a specific component of adaptive immunity present at early development. Native immunoglobulin belonging to the class of IgM is abundantly present in neonates and children and is known for its recognition of self- and altered self-antigens. Native IgM may be able to neutralize virus by the recognition of endogenous "danger signal" encoded in the viral envelope and originally imprinted in the membranes of infected and stressed cells. Noteworthy, thrombosis and vasculitis, two symptoms in severely affected adult and pediatric patients are shared between COVID-19 and patients with Behcet's disease, an autoimmune disorder exhibiting a region-specific prevalence in countries of the former silk road. Molecular mechanisms and clinical indicators suggest reactive oxygen species as trigger factor for severe progression of COVID-19 and establish a link to the innate immune defense against bacteria. The selective pressure exerted by bacterial pathogens may have shaped the genetics of inhabitants at this ancient trade route in favor of bacterial defense, to the detriment of severe COVID-19 progression in the 21th century.
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