The Cross-Talk between Age, Hypertension and Inflammation in COVID-19 Patients: Therapeutic Targets

Abstract

This paper presents a brief overview of the complex interaction between age, hypertension, the renin–angiotensin–aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, ‘inflammaging’, which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.

Risk Factors and Blood Pressure Control Targets Associated With the Clinical Outcome of Elderly COVID-19 Patients With Hypertension: a Retrospective Cohort Study

“…K-M analyze, univariate and multivariate Cox hazard analysis in the total patients con rmed that hypertension is the most independent risk factor of developing adverse clinical outcome in elderly COVID-19 patients, which consistent with previous research (14,15). The pathophysiologic mechanisms are generally believed to be the following two aspects: a critical interaction between SARS-CoV-2 and the angiotensin-converting enzyme 2(ACE2) (16, 17); the hypotension medicines which act on ACE2 (18,19).…”

Predicting COVID-19—Comorbidity Pathway Crosstalk-Based Targets and Drugs: Towards Personalized COVID-19 Management

“…ACE2 is a key enzyme that regulates the renin-angiotensin system associated with hypertension. Therefore, the crosstalk between hypertension and COVID-19 is mediated by the renin-angiotensin system [ 29 , 72 ]. Our analysis also found that the renin-angiotensin system is shared by hypertension and COVID-19.…”

“…The treatment’s efficacy could be increased if the molecular pathway crosstalk between the specific comorbidity and COVID-19 is understood and that crosstalk-based targets and targeting drugs are used towards personalized medication. Although, some reports are available such as crosstalk between COVID-19 and breast cancer [ 24 , 25 ], COVID-19 and Alzheimer’s disease [ 26 ], COVID-19 and ischemic stroke [ 27 ], hyperthyroidism and COVID-19 [ 28 ], COVID-19 and age, and COVID-19 and hypertension [ 29 ]; omics-based molecular pathway crosstalk between COVID-19 and its associated vital comorbid conditions and those crosstalk-based targets have not been investigated.…”

Drug exposure may have a substantial influence on COVID-19 prognosis among residents of long-term care facilities: an exploratory analysis

“…It is worth noting that the interaction between inhaled corticoids, ACE-2 antagonists and statins and Covid-19 is most probably mediated by their effect as inflammatory modulators, at the local level in alveolar epithelia (ACE-2 inhibitors and inhaled corticoids) or systemically (statins). Given that ageing is related to a more pro-inflammatory status ( Casucci et al, 2020 ) our observations may not be easily translated to the general population. Furthermore, the protective effect of these drugs could be due to long-term intake having caused chronic changes in the tissues targeted (i.e.…”