Potential risk for developing severe COVID-19 disease among anabolic steroid users.

A severe case of COVID-19 was observed in an otherwise healthy 28-year-old man who had taken oxandrolone 40 mg/day as an anabolic steroid. The patient had been taking oxandrolone for enhanced bodybuilding 30 days prior to presenting to an outpatient clinic with COVID-19 symptoms. The patient reported that his symptoms have rapidly worsened over the course of 4 days prior to presenting at the clinic. As part of an experimental antiandrogen treatment for hyperandrogenic men suffering from COVID-19, he was administered a single 600 mg dose of the novel antiandrogen proxalutamide. Twenty-four hours after administration of this dose, marked improvement of symptoms and markers of disease severity were observed. To our knowledge, this is the first case that potentially links anabolic steroid use to COVID-19 disease severity.

Are night shift workers at an increased risk for COVID-19?

Recent data has revealed an association between coronavirus disease-19 (COVID-19) incidence and seasonally regulated androgen sensitivity. This potential relationship between SARS-CoV-2 infection and clock genes, coupled with previously reported effects of night shift work on health, leads us to hypothesize that night shift workers may be at an increased physiological risk of coronavirus disease-19 (COVID-19). Shift work, especially night shift work, has long been associated with several chronic health conditions. The mechanisms that drive these associations are not well understood; however, current literature suggests that the disruption of circadian rhythms may cause downstream hormonal and immune effects that render night shift workers more susceptible to disease. First, circadian rhythms may play a role in the mechanism of viral infection, as viral vaccines administered in the morning elicit greater immune responses than those administered in the afternoon. Next, increased exposure to light at night may inhibit the production of melatonin, which has been observed to enhance DNA repair and shown to upregulate expression of Bmal1, an established inhibitor of herpes simplex virus and influenza. Finally, abnormal immune cell and cytokine levels have been observed following night-shift work. These data suggest that further research is warranted and that high-risk occupations should be taken into consideration as public health policies are introduced and evolve.

Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS).

In coronavirus disease-19 (COVID-19), four major factors have been correlated with worse prognosis: aging, hypertension, obesity, and exposure to androgen hormones. Angiotensin-converting enzyme-2 (ACE2) receptor, regulation of the renin-angiotensin-aldosterone system (RAAS), and transmembrane serine protease 2 (TMPRSS2) action are critical for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry and infectivity. ACE2 expression and RAAS are abnormal in hypertension and obesity, while TMPRSS2 is overexpressed when exposed to androgens, which may justify why these factors are overrepresented in COVID-19. Among therapeutic targets for SARS-CoV-2, we hypothesized that spironolactone, a long used and safe mineralocorticoid and androgen receptors antagonist, with effective anti-hypertensive, cardioprotective, nephroprotective, and anti-androgenic properties may offer pleiotropic actions in different sites to protect from COVID-19. Current data shows that spironolactone may concurrently mitigate abnormal ACE2 expression, correct the balances membrane-attached and free circulating ACE2 and between angiotensin II and Angiotensin-(1-7) (Ang-(1-7)), suppress androgen-mediated TMPRSS2 activity, and inhibit obesity-related RAAS dysfunctions, with consequent decrease of viral priming. Hence, spironolactone may provide protection from SARS-CoV-2, and has sufficient plausibility to be clinically tested, particularly in the early stages of COVID-19.