INDEX

Covid-19 Infection and Subsequent Pathology are Caused by

Low Dehydroepiandrosterone (DHEA)

(New support: Low DHEA in Covid-19)

New research, 2022, regarding DHEA has been published that supports my hypothesis that Covid-19 is caused by low DHEA: “COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity,” ( 2022 Jul 30. doi: 10.1007/s12020-022-03140-6.) “DHEA was an independent indicator of the disease severity with COVID-19.”

It is my hypothesis that Covid-19 infection and subsequent pathology are caused by low levels of dehydroepiandrosterone (DHEA) which are affected by aging, testosterone and cortisol levels, and antagonism of DHEA by cortisol as in stress, all of which reduce effects of DHEA (© Copyright 2020, James Michael Howard, Fayetteville, Arkansas, U.S.A.). It is already known that DHEA provides protection from pathogenic viruses. “In this study it was shown that DHEA protects mice against WNV, SVNI and SFV lethal infection.” (Arch Virol. 1991;120(3-4):263-71. doi: 10.1007/BF01310481.) High testosterone levels affect DHEA levels by decreasing available DHEA by reducing conversion of DHEA sulfate to the active form, DHEA, and low testosterone levels reduce intracellular DHEA; both reduce DHEA. This is why high levels of testosterone in males and high levels of testosterone of blacks compared to whites increase Covid-19 virulence, therefore, drugs such as dexamethasone, which is known to reduce testosterone reduce Covid-19 This is why reduced DHEA and testosterone of aging increases Covid-19 virulence.

Regarding the “cytokine storm” in Covid-19 infection, a case may be made that these cytokines are produced by cells / tissues to stimulate DHEA production. Therefore, the reduction in DHEA caused by Covid-19 would cause numerous tissues to produce cytokines to stimulate DHEA. Individuals who do not recover significantly by eventually producing DHEA experience “long covid.”

This is derived from my explanation of human evolution involving DHEA (mammalian evolution) and human evolution involving DHEA and testosterone. I suggest testosterone directly affects levels of DHEA and testosterone is increasing throughout human history and is ongoing. At this time I think testosterone has increased in human populations sufficiently to adversely affect DHEA levels. I suggest this is why human populations are experiencing increases in obesity, type 2 diabetes, cancer, infections, at this time, including Covid-19. (Note: some consider obesity as the cause of the others; obesity is simply the earliest sign.)

Since I think these androgens and their ratio control all aspects of the human life span, I think they are involved in all aspects of normal ontogeny as well as pathology. I suggest this is why Covid-19 has been connected with many pathologies as well as disturbances in cytokines, including “hypertension, diabetes, obesity, COPD, and CVD.”

As I stated above, I think testosterone is increasing with time within populations; an over abundance of testosterone can reduce the effects of DHEA and this is why pandemics are occurring, such as the HIV and others at this time. This is why Covid-19 is occurring at this time and is directly connected to other pathology. They are both caused by low DHEA.

“Hormones in Mammalian Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 177-184. If your library does not subscribe to “Rivista … ,” you may find this at: http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm .

Androgens in Human Evolution, Rivista di Biologia / Biology Forum 2001; 94: 345-362. If your library does not subscribe to Rivista , you may find this at: http://anthropogeny.com/Androgens%20in%20Human%20Evolution.htm where you may also see a chart of testosterone in humans and great apes which directly supports my hypothesis and was reported in the literature 2 years later.

New connections of low DHEA and Covid-19, January, 2023: Low DHEA has been found in “burning mouth (BM),” (Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Oct;108(4):537-43. doi: 10.1016/j.tripleo.2009.06.022. PMID: 19778740.). “Glossodynia [burning mouth] is significantly more common in COVID-19 patients and should be considered in the differential diagnoses among the oral complications of this infection.” (Am J Dent 2022;35:9-1. 2022 Feb;35(11) :9-11

I invite you to read my explanation of Down’s Syndrome which includes a direct explanation of the connection of maternal age in the etiology.

Down's Syndrome, Trisomy 21, Dehydroepiandrosterone (DHEA), and DNA Methylation: a Possible Explanation

© Copyright 2020 James Michael Howard, Fayetteville, Arkansas, U.S.A.

The cause of Down's syndrome (DS) may be low levels of maternal dehydroepiandrosterone (DHEA) in utero. This includes DNA associated characteristics as well as the chromosome 21 aneuploidy. ("DHEA supplementation to a significant degree reduced number (P = 0.029) and percentages (P < 0.001) of aneuploid embryos, adjusted for relevant covariates. Short term supplementation (4-12 weeks) resulted in greatest reduction in aneuploidy (21.6%, 95% CI -2.871-46.031)." Reprod Biol Endocrinol. 2010; 8: 140.
Published online 2010 Nov 10. doi: 10.1186/1477-7827-8-140 ) DHEA naturally peaks around ages of 20-25 years, declining, thereafter, to very low levels in old age. DS is characteristically found in offspring of women 35-years-old or later. The “DNA associated characteristics” are the basis of my explanation of DS. (This is derived from my explanations of mammalian and human evolution; citations for these are at the end of this treatise.)

I think DHEA is directly involved in all DNA, gene, activity. A ratio of DHEA and DNA is disturbed by increased DNA, extra chromosome 21, in Down’s syndrome, that is, the ratio of DHEA to DNA is reduced. This may be demonstrated by DNA methylation patterns. I first suggested DHEA is involved in DNA methylation in 2015. "I suggest DNA methylation is an evolutionary consequence of reduced levels of dehydroepiandrosterone (DHEA) and is involved in cancer initiation." ("DNA Methylation, DHEA, and Cancer," http://anthropogeny.com/DNAmethDHEAcancer.html ) Again, DHEA naturally begins to decline in women around ages 20-25. reaching very low levels in old age; I suggest it is the low DHEA of women around age 35 that is the cause of Down syndrome. Low DHEA has been reported in Down's syndrome J Neuroendocrinol. 2011 May;23(5):450-5. doi: 10.1111/j.1365-2826.2011.02118.x ).

A study of DNA methylation in DS reported that "Overall, our results indicate that the chorionic villi cells of DS [Down syndrome] fetuses are hypermethylated in all autosomes and suggested that altered DNA methylation may be a recurrent and functionally relevant downstream response to DS in human cells." ( Clin Epigenet 11, 180 (2019). https://doi.org/10.1186/s13148-019-0756-4 ). This means that all of these chromosomes may be affected by the low DHEA to DNA ratio in DS.

I suggest the low ratio of DHEA to DNA is the cause of Down’s syndrome aneuploidy and the resultant characteristics of Down's syndrome. Measurements of, and adjustment thereof, DHEA in pregnant women, or those intending to become pregnant, should be performed on all women. (For sake of support, low DHEA in young women has been determined to reduce pregnancies.)

“Hormones in Mammalian Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 177-184. If your library does not subscribe to “Rivista … ,” you may find this at: http://anthropogeny.com/Hormones%20in%20Mammalian%20Evolution.htm .

“Androgens in Human Evolution,” Rivista di Biologia / Biology Forum 2001; 94: 345-362. If your library does not subscribe to “Rivista … ,” you may find this at: http://anthropogeny.com/Androgens%20in%20Human%20Evolution.htm where you may also see a chart of testosterone in humans and great apes which directly supports my hypothesis and was reported in the literature 2 years later.

Covid-19 is Cause of Current Increased Virulence

of RSV and Influenza

I suggest the basis of increased virulence of Respiratory Syncytial Virus and influenza at this time is reduction of dehydroepiandrosterone (DHEA) caused by Covid-19. It is my hypothesis that Covid-19 infection and subsequent pathology are caused by low DHEA. Support of low DHEA associated with Covid-19 virulence has recently been reported. It has been determined that DHEA stimulates / increases antibody formation in aged mice: “When DHEA was provided either topically or was incorporated directly into vaccine, vigorous primary and secondary antibody responses were detected in the aged mice given a single administration of DHEA, regardless of the mode of administration.” (The Journal of Infectious Diseases No. 4 (Apr., 1993), pp. 830-840 ).

I submit the Covid-19 pandemic has reduced DHEA throughout the world, which has reduced the antibody response to RSV and influenza. I suggest this is the cause of the ongoing increase in RSV and influenza. This may also explain the common increase in Covid-19, influenza, and RSV in the United States at this time. We may have discarded our prophylaxis of Covid-19 infection too early.

Further support and regarding the current increase in Respiratory Syncytial Virus: It has been reported that “High PRL [prolactin] serum level or hyperprolactinemia is associated with different viral infections.” (Mol Cell Biochem 477, 1381–1392 (2022). https://doi.org/10.1007/s11010-022-04381-9 )

Prolactin is a direct and specific stimulant of DHEA; high PRL indicates an immune response to increase DHEA. “there seems to be a correlation between prolactin signalling and severity of infection [RSV]” (“Respiratory syncytial virus (RSV): a scourge from infancy to old age,” BMJ “Thorax” https://doi.org/10.1136/thoraxjnl-2018-212212 )