Mild SARS-CoV-2 infections in children might be based on evolutionary biology and linked with host reactive oxidative...

Area of Science:

• Immunology
• Evolutionary Biology
• Gerontology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disproportionately affects elderly individuals, causing significant morbidity and mortality.
• Children generally exhibit milder illness, with rare fatalities, despite similar exposure risks.
• The disparity in disease severity across age groups remains unexplained.

Purpose of the Study:

• To investigate the underlying biological mechanisms contributing to differential SARS-CoV-2 disease severity in children versus the elderly.
• To propose a unifying hypothesis based on evolutionary biology and redox state.

Main Methods:

• Review of existing literature on SARS-CoV-2, age-related physiological differences, antioxidant capacity, and immune modulation.
• Analysis of evolutionary principles and translational research findings.
• Correlation of redox state and angiotensin-converting enzyme 2 (ACE2) expression with disease outcomes.

Main Results:

• Children possess higher endogenous antioxidant capacity, maintaining a balanced redox state crucial for mitigating SARS-CoV-2-induced inflammation.
• Elderly individuals exhibit diminished antioxidant capacity and lower ACE2 expression, predisposing them to severe disease.
• Redox-sensitive immune modulation appears to be a key factor in age-related differences in infection severity.

Conclusions:

• The high antioxidant capacity in children is a primary factor for their milder SARS-CoV-2 infections.
• Reduced antioxidant capacity and ACE2 expression in the elderly contribute to their vulnerability to severe SARS-CoV-2 outcomes.
• Targeting redox balance and ACE2 pathways may offer therapeutic strategies for severe COVID-19 in older populations.