Maternal Diet During Pregnancy and COVID-19 Susceptibility of Offspring: The “Thrifty Phenotype Hypothesis” Connection

There are accumulating evidence suggesting that ACE2, the host cell receptor for the spike (S) protein of the SARS-CoV-2, which mediates viral entry and infection, is under epigenetic control.  In this review, we discuss studies suggesting a nutritional strategy for down-regulating ACE2 expression in tissues of offspring through the phenomenon of maternal epigenomic reprogramming mediated by maternal diet.  Consistent with the "thrifty hypothesis", first proposed by Hales and Barker, which posits that specific genes are programmed based on early-life experience to promote efficient fat deposition and storage in adulthood, the analysis of the proposed mechanism for "early life programming" via nutritional modulation of histone acetylation and DNA methylation goes beyond the physiological consequence of boosting the innate cellular resistance to viral transmission. During the pandemic where there is still no specific antiviral drug or vaccine for COVID-19, we hypothesize that a nutrition epigenomic approach may be a practical approach to help mitigate viral transmission to the offspring.