I would like to link three papers recently published in your journal with regard to COVID-19.
First, Gan et al. focus on angiotensin converting enzyme 2 (ACE2). They put forward the hypothesis that COVID-19 is an “ACE2 deficiency disorder, with ACE2 related multi-organ cell loss” [1].
Second, Soumier and Sirigu propose oxytocin as a defence against COVID-19 because of its immune modulating properties and other auxiliary mechanisms [2].
Third, Silberstein brings to light a possible treatment for COVID-19 proposing the use of vitamin D to modulate the cytokine storm [3].
At first glance, these three disparate papers have no observable link apart from COVID-19. Are COVID-19, ACE2, oxytocin and vitamin D enigmatically entangled? What of Occam's razor; is there a single unifying link? Yes, I believe there is: the oxytocin producing neurone.
It is known that oxytocin is produced in the hypothalamus and transported to the pituitary gland where it is released systemically. ACE2 and transmembrane serine protease 2 (TMPRSS2) are thought to be required for SARS-CoV-2 cell entry. Both ACE2 and TMPRSS2 have been identified in the hypothalamus [4] and ACE2 has been located directly on the oxytocin neurone [5]. The vitamin D receptor has also been localised to oxytocin neurones, and there is data to suggest that vitamin D can increase oxytocin levels [6].
I would conclude with this hypothesis: hypothalamic oxytocin neurones could be infected by SARS-CoV-2, via ACE2 and TMPRSS2, leading to neuronal dysfunction or death with subsequent reduction in oxytocin production. In addition, oxytocin production may be limited by vitamin D deficiency. The reduction in plasma oxytocin could increase COVID-19 severity and be part of the “long COVID” phenomenon.
Therefore I would reiterate the need for further research into the proposed use of oxytocin for COVID-19.
Funding
There are no grants or funding associated with this work.
Declaration of Competing Interest
The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References
- 1.Gan R., Rosoman N.P., Henshaw D.J.E., Noble E.P., Georgius P., Sommerfeld N. COVID-19 as a viral functional ACE2 deficiency disorder with ACE2 related multi-organ disease. Med Hypotheses. 2020;144 doi: 10.1016/j.mehy.2020.110024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Soumier A., Sirigu A. Oxytocin as a potential defence against Covid-19? Med Hypotheses. 2020;140 doi: 10.1016/j.mehy.2020.109785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Silberstein M. Vitamin D: a simpler alternative to tocilizumab for trial in COVID-19? Med Hypotheses. 2020;140 doi: 10.1016/j.mehy.2020.109767. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.S. Nampoothiri, F. Sauve, G. Ternier, et al. The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis bioRxiv 2020.06.08.139329.
- 5.Lazartigues E, Qadir MMF, Mauvais-Jarvis F, Endocrine Significance of SARS-CoV-2's Reliance on ACE2 Endocrinology, 161 (2020), Article bqaa108. [DOI] [PMC free article] [PubMed]
- 6.Patrick R.P., Ames B.N. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J. 2014;28:2398–2413. doi: 10.1096/fj.13-246546. [DOI] [PubMed] [Google Scholar]