系统发生学与进化生物学杂志

Bat evolution, demographic data, and pre-existing conditions solve mystery of COVID-19 infection severity

Abstract

Felice L. Bedford

It is hypothesized that the reason behind coronavirus severity stems from the unique adaptations in bats, where the virus co-evolved, to accommodate flight which generates large amounts of oxygen free radicals. Oxidative stress, particularly through excess endogenous Nicotinamide Adenine Dinucleotide Phosphate Hydrogen (NADPH) oxidase production of superoxide, is the single unifying framework for explaining the large range of risk factors for severe coronavirus infection including aging, male gender, African- American race, cardiovascular disease, obesity, and diabetes. Evidence is presented that death rate as a function of age better resembles the near-exponential rise seen in cancer, where oxidative stress is high, rather than the historical W or U-shaped functions of pandemic or seasonal flu. In addition, consideration of more than 10,000 Center for Disease Control and Montgomery County, Pennsylvania publicly available cases suggested a deviation from an exponential rise in the oldest-old, consistent with lower oxidative stress levels reported in that group. Gender analyses unexpectedly found male-to-female risk of mortality to be an inverted U-shaped function peaking at nearly 2.5 times from age 30 to 50 and may reverse to half the female risk at the oldest ages, providing a good fit to known oxidative stress gender differences across the lifespan. Race data were consistent with higher mortality from COVID-19 and higher oxidative stress levels in African Americans. It is argued pre-existing conditions that increase risk all share high oxidative stress levels while, intriguingly, the possibly protective Inflammatory Bowel Disease and Lupus have low levels of NADPH oxidase-derived oxygen free radicals. Strategies for prevention and treatment that follow from the theory are briefly covered including N-acetyl cysteine in older men to restore glutathione levels to more youthful values and especially exciting, pursuing the inhibition of NADPH oxidases not only with well-known melatonin but also with less known compounds such as the naturally occurring apocynin, which is also inexpensive and readily available.