PA and COVID-19

Association between plasma aldosterone level and disease severity was first reported by French researchers in July 2020

In an article published in August 2020, Italian researchers reported the case of a 47-year-old female with primary aldosteronism who developed a severe form of COVID-19 requiring ICU hospitalization. The authors hypothesized that, because of its effect on Interleukin-6 (a pro-inflammatory cytokine involved in the storm caused by SARS-CoV2), elevated aldosterone is likely associated with severe infection of the lungs and endothelial cells. They recommended serum aldosterone assessment in all patients with COVID-19, and the use of Tocilizumab to inhibit the effects of increased Interleukin-6.

In February 2021, results from a cohort study conducted at the University College London Medical School showed that, compared with normal sodium, hyponatremia was associated with a twofold increase in likelihood of respiratory failure. Hypernatremia was associated with a threefold increase in likelihood of death. These findings support earlier reports indicating that a significant number of patients hospitalized with severe forms of COVID-19 develop hypokalemia, and that disease severity correlates with the severity of hypokalemia.

Vaccination

There are multiple safe and effective vaccines that prevent people from becoming seriously ill or dying from COVID-19. They are especially important for people with underlying conditions such as PA. Vaccination is also the best way to prevent the spread of the virus to others in the community.  

Since the vaccines and the virus are new, there is uncertainty on the level of immunity and how long it will last, but strong effectiveness has been confirmed up to 6 months. Approved vaccines have also proven effective against new variants, although that could change and a booster shot may be needed in the future.

The new mRNA vaccines from Pfizer-BioNtech and Moderna are exceptionally effective (>94%). Even so, the more traditional AstraZenica/Oxford and J&J vaccines are also effective at preventing severe disease and death. While they have been linked to blood clots in a very small number of cases, WHO, CDC, and EU advise that the benefits of vaccination far outweigh these risks. Russia, China, and India have also developed effective vaccines.

Spironolactone May Be Protective

Spironolactone counteracts some of the factors enabling SARS-CoV-2 to cause infection (i.e., abnormal ACE2 expression, angiotensin II and 1-7 imbalance, and androgen activity).

Early in the pandemic, studies conducted in Russia as well as Brazil and the United States indicated that the drug could be considered for prophylactic and early treatment of COVID-19 (i.e., to slow the virus entry into cells and decrease the severity of fibrosis in various organs, including the lungs).

Researchers in Poland and the United States have since confirmed the benefits of the drug, and emphasized the need for prospective clinical trials. In contrast, a South Korean study concluded that while spironolactone may reduce susceptibility to COVID-19, it does not prevent associated complications.

Role of Cortisol

Cortisol activation of the mineralocorticoid receptor in infected cells plays an important role in the most severe forms of COVID-19.

Dexamethasone, a corticosteroid, is therefore used to improve survival in hospitalized patients who require supplemental oxygen and mechanical ventilation.

Researchers in the UK have suggested that dexamethasone could offer a more effective MR blockade if combined with an MR antagonist such as spironolactone.

References

  • Villard, O.; Morquin, D.; Molinari, N.; Raingeard, I.; Nagot, N.; Cristol, J.-P.; Jung, B.; Roubille, C.; Foulongne, V.; Fesler, P.; Lamure, S.; Taourel, P.; Konate, A.; Maria, A.T.J.; Makinson, A.; Bertchansky, I.; Larcher, R.; Klouche, K.; Le Moing, V.; Renard, E.; Guilpain, P. The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study. J. Clin. Med. 2020, 9, 2315., DOI: 10.3390/jcm9072315
  • Ploutarchos Tzoulis, Julian A Waung, Emmanouil Bagkeris, Ziad Hussein, Aiyappa Biddanda, John Cousins, Alice Dewsnip, Kanoyin Falayi, Will McCaughran, Chloe Mullins, Ammara Naeem, Muna Nwokolo, Helen Quah, Syed Bitat, Eithar Deyab, Swarupini Ponnampalam, Pierre-Marc Bouloux, Hugh Montgomery, Stephanie E Baldeweg, Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19, The Journal of Clinical Endocrinology & Metabolism, Volume 106, Issue 6, June 2021, Pages 1637–1648. DOI: 10.1210/clinem/dgab107
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  • Cadegiani FA, Goren A, Wambier CG. Spironolactone may provide protection from SARS-CoV-2: Targeting androgens, angiotensin converting enzyme 2 (ACE2), and renin-angiotensin-aldosterone system (RAAS). Med Hypotheses. 2020;143:110112. DOI: 10.1016/j.mehy.2020.110112.
  • Kotfis K, Lechowicz K, Drożdżal S, Niedźwiedzka-Rystwej P, Wojdacz TK, Grywalska E, Biernawska J, Wiśniewska M, Parczewski M. COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection. Pharmaceuticals. 2021; 14(1):71. DOI: 10.3390/ph14010071.
  • Wilcox, Christopher S. MD, PhD; Pitt, Bertram MD Is Spironolactone the Preferred Renin–Angiotensin–Aldosterone Inhibitor for Protection Against COVID-19?, Journal of Cardiovascular Pharmacology: March 2021 – Volume 77 – Issue 3 – p 323-331 DOI: 10.1097/FJC.0000000000000960.
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  • RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. DOI: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
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The Primary Aldosteronism Foundation is a registered 501(c)(3) public charity. Donations are tax deductible in the US.

©2021 Primary Aldosteronism Foundation

The Primary Aldosteronism Foundation is a registered 501(c)(3) public charity. Donations are tax deductible in the US.