Abstract
AimsPatients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity.Methods and resultsWe analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators.ConclusionThese data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.
Highlights
The corona virus disease 2019 (COVID-19) pandemic imposes a significant burden on health care systems [1]
These data suggest a beneficial effect of angiotensin II receptor blockers (ARBs) on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity
Patients with comorbid conditions including hypertension and cardiovascular diseases are highly represented among patients, who suffer from a critical course of COVID-19 and eventually succumb to the disease, indicating that these comorbidities may predispose to increased aggressiveness of the infection in this group [4, 5]
Summary
The corona virus disease 2019 (COVID-19) pandemic imposes a significant burden on health care systems [1]. The Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS-CoV-2) enters the cell by binding of its trimeric spike protein to the human receptor angiotensin-converting enzyme II (ACE2) expressed on epithelial cells in the respiratory system [7]. Animal studies showed that ACEIs and ARBs can upregulate ACE-2 [9], which raised concerns whether a higher availability of the entry receptor for SARS-CoV2 might result in increased infection rates and higher disease severity in patients with RAAS modulating drugs. Association of ACEi/ARB use with outcomes in patients with COVID-19 revealed conflicting results with respect to disease progression with most studies reporting neutral or even beneficial effects of blockade of the renin angiotensin aldosterone system (RAAS) [10,11,12]
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