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.