Neuropathological explanation of minimal COVID-19 infection rate in newborns, infants and children - a mystery so far. New insight into the role of Substance P.

Sars-Cov-2 or Novel coronavirus infection (COVID-19) has become a global challenge, affecting elderly population at large, causing a burden on hospitals. It has been affecting the world from a health and economic perspective after its emergence since October 2019 at Wuhan province of China. Later on it became a pandemic, with aged people most affected. Surprisingly, the infants and children were not severely infected and mortality among them was reported infrequently. If they died it was due to some comorbidity or congenital heart problems. Why the rate of infection varies in different age groups around the world and what is the protective mechanism in children remains a mystery. Based on our neuropathological experience at the "Lino Rossi Research Center for the study and prevention of the unexpected perinatal death and Sudden Infant Death Syndrome (SIDS)" of the University of Milan, Italy, we hypothesize that the decreased severity of the disease in infants compared to the elderly may be due to alteration at neurotransmitter levels especially of the Substance P (SP) and of the spinal trigeminal nucleus in the brainstem that is responsible for its secretion. This neurotransmitter may be directly related to the respiratory illness as is in COVID-19 infection. It is responsible for the increased inflammation and the characteristic symptoms associated with this disease. It is the main switch that must be urgently turned off using the NK-1R antagonist which is the receptor of SP and responsible for its functionality, especially in the elderly.