RAAS treatments in Covid-19
The role of ACE2 in COVID-19 and the protective role of ACE2 in
different organs has recently been reviewed. Clinical trial and
retrospective data pertaining to RAAS treatments during COVID-19 are
beginning to surface. In one retrospective study looking at ARB use in
COVID-19 patients, ongoing use of these medications compared to other
hypertensive treatments, was associated with lower risk of all-cause
mortality compared with ACEI/ARB non-users (adjusted HR 0.30; 95% CI,
0.12-0.70; P=0.01). (14) Another study also confirmed a lower risk of
mortality (relative risk 0.65, 95% CI 0.45-0.94, P= 0.02). (15)
Statin drugs, which prevent ART-mediated activation of Nox and reduce
oxidative stress, recently showed a lower crude 28-day mortality (IRR
0.78; 95% CI, 0.61-0.996; p=0.046) in COVID-19. (16) Equally,
dexamethasone showed a reduced risk of 28-day mortality (age-adjusted
ratio 0.83; 95% CI 0.743-0.92; P<0.00). (17)
Although ARBs are not being used as de-novo treatment during COVID-19,
current recommendations and consensus is to continue established
treatment. There is little discussion of either statin drugs or MR
blockers in COVID-19. As with ARBs, discontinuing these RAAS-modifying
medications should not be taken lightly in view of the acute RAAS stress
experienced during this illness.
Confirming the “Covid Syndrome” hyperaldosterone hypothesis would
require the measurement of renin/aldosterone levels and their
correlation with serum cytokine levels and disease severity and
outcomes. Cytokine levels, particularly IL-6, have been shown to predict
outcome. Electrolyte and blood pressure levels are unlikely to directly
correlate with aldosterone levels due to many confounding variables and
influences. Elevated aldosterone levels with low/normal renin could
result from ACE2-depletion/Ang II-mediated stimulation.
This hypothesis advocates for the use of a cocktail of medications that
counter the acute loss of ACE2 during “Covid Syndrome” by blocking the
downstream effects of acutely increased Ang II activity. These
medications would include dexamethasone, ARBs and MRBs such as
spironolactone and eplerenone. (18) Supportive treatment with a statin
drug could also be included, but may not add much benefit in combination
with the aforementioned drugs. (16) All of these medications are readily
available worldwide and have established safety and efficacy records
when used, including in combination, in patients with severe
RAAS-mediated disease. (19,20) Patients who recover from severe illness
often experience severe fibrosis of the lungs, heart and kidneys.
Blocking RAAS until complete resolution of the cytokine storm is
achieved may reduce these debilitating long-term effects.
Acknowledgements: No funding was sought or provided for
preparation of the current work.
The author would like to thank Ngoc Nguyen for her assistance with
preparation of the summary schematic (Figure 1).
Declaration of Interests: Dr. Henry currently has a patent
application pending for the use of mineralocorticoid receptor (MR)
blockers for the treatment of COVID 19.