3b. Predisposition and comorbidities e.g. hypertension,
other vascular disease and diabetes.
Much has been written recently on the relationship between hypertension
and COVID-19 disease. Patients with severe COVID-19 are often older and
with a history of hypertension as seen for example in 75% of patients
that died in the COVID-19 pandemic in Italy had hypertension (11).
As indicated earlier ACE2 is not only the target for SARS-CoV-2 but
functionally balances the pulmonary and possibly vascular
RAS/inflammation axis. Therefore, a potential increase in ACE2 mediated
with antihypertensives, that act to inhibit RAAS, raised potential
concerns with patients with COVID-19. There was insufficient data to
determine whether these findings translated to humans and that clinical
trials were underway to test these inhibitors in COVID-19 (41).
Furthermore, Kreutz et al (11) indicated that after a review of the
evidence there was currently no reason to discontinue RAS blockers in
stable patients in the COVID-19 pandemic.
Consistent with this view there are now a growing number of studies
based on medical records of hospitalized COVID patients that do not
indicate a deterioration of patients with RAS inhibition and to varying
extents an improvement in outcomes when compared to patients not treated
with RAS inhibitors (42-45). From the preceding studies however, it is
not apparent whether the RAS inhibitors were maintained during
hospitalisation or possibly ceased upon admission. This may be an
important consideration based upon the results of previous studies with
patients with viral pneumonia. Mortensen et al (50) showed that both
prior and continued ACEI was associated with decreased mortality and
length of stay in hospitalised patients with pneumonia. Henry et al (46)
determined the effects of ACEIs and ARBs in patients with viral
pneumonia, finding that patients on ACEIs prior to admission and
subsequently discontinued had a higher mortality than those not on ACEIs
prior to admission and there was a decrease in intubation or mortality
in patients with continued use of ACE inhibitors during hospital
admission. These results illustrate the importance of
administrative/observational data consistent with the view that
observational studies based on both big and small data sets are useful
in understanding how to treat viral disease (4).
What is of significance is the emerging understanding that
cardiovascular disease like COVID-19. is a partially inflammatory state.
In addition to the extensive discussion on hypertension and
cardiovascular disease in COVID-19 there is a increasing body of
evidence a role of inflammation and immunity in hypertension and
cardiovascular disease (47). For example, there is a growing
appreciation of the role of oxidative stress in the arterial wall,
inflammatory infiltration, regulatory and interleukin 17 producing
T-cells leading the development of hypertension (48).
A role for inflammation in hypertension is documented as is a powerful
role of inflammation in COVID-19 disease (13). It is not surprising with
this confluence that hypertension and related vascular disorders enhance
susceptibility to this disease. It follows that from a repurposing
standpoint a growing view would be not to abandon RAS inhibitors
but rather explore their potential as repurposing agents in COVID-19.