Fact check: Spironolactone and COVID-19

Disclaimer: I am not a medical professional and this is not medical advice. Our understanding of the pandemic is evolving rapidly; this information may be superseded by later and more conclusive findings. This article was last updated on March 31, 2020.

Zinnia JonesAs the SARS-CoV-2 coronavirus, the virus that causes COVID-19, has cut a deadly path around the globe, many people have desperately sought out potential treatments that could reduce the severity of the disease or the risk of contracting it. From the apparently unsupported rumor that ibuprofen worsens COVID-19 in those who have it, to the startlingly weak evidence for the use of hydroxychloroquine to treat the infection, a vulnerable population – and right now, that’s every one of us – badly wants to believe there’s something that can be done in the face of a potentially lethal virus.

This has come to intersect with the trans community in the case of spironolactone, a blood pressure medication often used for its testosterone-blocking effects as part of feminizing hormone therapy by trans women and transfeminine people who have not yet undergone gonadectomy (orchiectomy or vaginoplasty). While other medications have been used to block the production or action of endogenous testosterone, spironolactone is among the most inexpensive and is widely used in the United States. Recently, concerns have been raised on social media and in beauty outlets that spironolactone may increase the likelihood of contracting COVID-19 or worsen the symptoms of the disease.

On March 21, POPSUGAR’s Beauty vertical quoted dermatologist Dr. Ellen Marmur as recommending that her patients stop taking spironolactone for acne (a condition often successfully treated by spironolactone in both cis and trans people):

The American Academy of Dermatology has not said to stop spironolactone. . . . But since we know that ACE inhibitors and spironolactone upregulate the number of receptors to possibly allow more virus to come into the cell based on this data, which is published . . . I would stop spironolactone. . . . It’s not medically necessary for acne. I’m only talking about my acne patients. I would stop the spironolactone until we know further.

RealSelf.com further cites an emergency physician and an OB-GYN who assert that there is a “theoretical” risk from spironolactone; other individuals on Twitter have repeated similar claims. But is there an actual danger here?

Marmur cites Keidar et al. (2005), a study of 10 patients treated with spironolactone for one month, as showing that spironolactone increased the activity of the ACE2 enzyme by 300%. ACE2 is known to be a receptor for SARS-CoV, the virus that causes SARS; Hamming et al. (2007) note that “autopsy specimens of patients who died of SARS revealed that ACE2-expressing cells are a direct target of SARS-CoV”. SARS-CoV-2 binds to ACE2 as the first step of viral entry into cells (Yan et al., 2020), suggesting the possibility that a greater expression of ACE2 induced by spironolactone could make it easier to contract the virus or could worsen the course of the disease.

That theoretical possibility, however, may not translate to a clinical reality. Sanchis-Gomar et al. (2020) point out that “increased expression would not necessarily imply increased risk of infection or disease severity”; Patel & Verma (2020) similarly note that “the significance of ACE2 expression on COVID-19 pathogenesis and mortality is not specifically known.” Perico et al. (2020) observe that ACE2 is not the only relevant factor here, and that “SARS-CoV-2 entry into target cells is a tightly regulated multi-step processes, of which binding to ACE2 is merely the first”. They further make note of a “paradoxical effect of ACE2 modulation on coronavirus infections”, presenting evidence that even suggests “ACE2 in the lungs may play a protective role in SARS-CoV-2 infection.”

Vaduganathan et al. (2020) echo these observations, stating that “data are lacking regarding the effects” of drugs such as spironolactone “on lung-specific expression of ACE2”, and that “clinical data are lacking to indicate whether this would in turn facilitate greater engagement and entry of SARS-CoV-2 spike protein.” They go on to suggest that because “SARS-CoV-2 appears not only to gain initial entry through ACE2 but also to subsequently down-regulate ACE2 expression such that the enzyme is unable to exert protective effects in organs”, medications that increase ACE2 activity may actually have a “potential for benefit rather than harm” for those with COVID-19. In a recent preprint, Dr. Flavio Cadegiani at the Adrenal and Hypertension Unit of the Federal University of São Paulo similarly proposes that “high-dose spironolactone may be considered in order to enhance circulating levels of ACE2”; Patel & Verma also noted that “preclinical data suggest a potential mechanism of benefit” from use of ACE inhibitors and angiotensin receptor blockers to increase expression of ACE2.

Major organizations of medical professionals have taken the position that there is not sufficient evidence to warrant discontinuing medications that raise ACE2 on the basis of a supposed increased risk of contracting COVID-19 or experiencing the disease more severely. The American Heart Association, Heart Failure Society of America, and American College of Cardiology stated on March 17 that “the evidence does not confirm the need to discontinue ACE-i or ARBs” and “there are no experimental or clinical data demonstrating beneficial or adverse outcomes among COVID-19 patients using ACE-i or ARB medications.” The European Society of Cardiology stated on March 13 that: “This speculation about the safety of ACE-i or ARB treatment in relation to COVID-19 does not have a sound scientific basis or evidence to support it. . . . The Council on Hypertension of the European Society of Cardiology wish to highlight the lack of any evidence supporting harmful effect of ACE-I and ARB in the context of the pandemic COVID-19 outbreak.” The European Medicines Agency stated on March 27 that there “is currently no evidence from clinical or epidemiological studies that establishes a link between ACE inhibitors or ARBs and the worsening of COVID-19”, and that “speculation that ACE-inhibitors or ARBs treatment can make infections worse in the context of COVID-19 is not supported by clinical evidence.”

At the present time, it appears there is not sufficient evidence to indicate that taking spironolactone could increase one’s likelihood of contracting COVID-19 or experiencing more severe symptoms, nor is there sufficient evidence of a beneficial effect of spironolactone on COVID-19. Professional medical organizations have stated that there are not adequate grounds to recommend that those on spironolactone should stop taking it.

As always, what we know on this topic may change as researchers and clinicians continue to learn about this disease. But of one thing we can be certain: This virus has infected hundreds of thousands of people who were not taking spironolactone, killing tens of thousands and leaving many others with permanent disabilities or injuries. Whether or not you’re on spironolactone appears to be a far less relevant factor than doing everything you can to avoid being exposed to this virus. COVID-19 can and has killed people who are young and who do not have underlying conditions – there is no group that is safe from this. Stay indoors; keep away from people; wash your hands frequently. This is a matter of survival – for yourself, for your loved ones, and for your community.

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About Zinnia Jones

My work focuses on insights to be found across transgender sociology, public health, psychiatry, history of medicine, cognitive science, the social processes of science, transgender feminism, and human rights, taking an analytic approach that intersects these many perspectives and is guided by the lived experiences of transgender people. I live in Orlando with my family, and work mainly in technical writing.
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2 Responses to Fact check: Spironolactone and COVID-19

  1. Daira Hopwood says:

    Thankyou, that was very thorough!

  2. Pingback: June COVID-19 update: Reassuring data on spironolactone and ACE2 risks | Gender Analysis

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