Abstract
As the COVID-19 pandemic is spreading around the world, increasing evidence highlights the role of cardiometabolic risk factors in determining the susceptibility to the disease. The fragmented data collected during the initial emergency limited the possibility of investigating the effect of highly correlated covariates and of modeling the interplay between risk factors and medication. The present study is based on comprehensive monitoring of 576 COVID-19 patients. Different statistical approaches were applied to gain a comprehensive insight in terms of both the identification of risk factors and the analysis of dependency structure among clinical and demographic characteristics. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2), but whether or not renin-angiotensin-aldosterone system inhibitors (RAASi) would be beneficial to COVID-19 cases remains controversial. The survival tree approach was applied to define a multilayer risk stratification and better profile patient survival with respect to drug regimens, showing a significant protective effect of RAASi with a reduced risk of in-hospital death. Bayesian networks were estimated, to uncover complex interrelationships and confounding effects. The results confirmed the role of RAASi in reducing the risk of death in COVID-19 patients. De novo treatment with RAASi in patients hospitalized with COVID-19 should be prospectively investigated in a randomized controlled trial to ascertain the extent of risk reduction for in-hospital death in COVID-19.
Highlights
As the COVID-19 pandemic is spreading around the world, increasing evidence highlights the role of cardiometabolic risk factors in determining the susceptibility to the disease
In contrast to other studies that used datasets collected on an emergency basis, with a high degree of heterogeneity and highly correlated covariates, we took advantage of a smaller but comprehensive dataset to characterize the interactions between cardiovascular risk factors, medication, and outcome, by means of an integrated statistical approach
The beneficial effect of renin−angiotensin−aldosterone system inhibitors (RAASi) has been masked by the high dependence on cardiovascular risk factors in previous studies and might reflect a direct impact of RAASi on the virus−host interaction, as previously observed in experimental models of SARS-CoV−induced lung injury displaying a protective role of blocking the RAAS [11, 18]
Summary
As the COVID-19 pandemic is spreading around the world, increasing evidence highlights the role of cardiometabolic risk factors in determining the susceptibility to the disease. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells by binding to the angiotensinconverting enzyme 2 (ACE2), but whether or not renin−angiotensin−aldosterone system inhibitors (RAASi) would be beneficial to COVID-19 cases remains controversial. The survival tree approach was applied to define a multilayer risk stratification and better profile patient survival with respect to drug regimens, showing a significant protective effect of RAASi with a reduced risk of in-hospital death. Older age and cardiovascular comorbidities are among the most important risk factors influencing the virus−host interaction and the clinical outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [4,5,6]. The SARS-CoV-2 virus enters host cells after binding to the angiotensin-converting enzyme 2 (ACE2), but whether renin−angiotensin−aldosterone system inhibitors (RAASi) are beneficial remains controversial. We provide strong evidence for protectivity of RAASi on hospitalized patients that call for randomized controlled trials of RAASi as COVID-19 treatment option
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