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To the Editor: The recently published study by Shi et al. [1] described a risk score that provides a rapid assessment tool for COVID-19 patients. This score relies on comorbid hypertension to extract a cutoff point that identifies patients at risk of worse outcomes. While the idea is more than worthwhile in the clinical context, it has omitted a critical epidemiological and biological point regarding SARSCoV-2: namely, ACE2 receptor hijacking. SARS-CoV-2, much like the structurally similar and precedent SARSCoV, uses the ACE2 receptor to establish host uptake [2]. On the basis that ARBs and ACE inhibitors, commonly used medications in the treatment of hypertension, are known to increase ACE2 mRNA expression, Fang et al. [3] have hypothesized that COVID-19 patients with comorbid hypertension, treated with said antihypertensives, may be at an increased risk for developing the more severe forms of respiratory disease. Given previous knowledge on the SARS-CoV modus operandi, ACE2-dependent uptake was shown to determine de novo cytotoxicity to pancreatic islet cells and the development of hyperglycemia and diabetes [4]. On the premises of the article determining a host risk score, the lack of analyses for the use of ACE2 inhibitors among hypertensive patients detracts from the value of the developed score. Given that the effect of both ACE inhibitors/ARBs on disease course is largely unknown and the focus of further investigation [5], relevant treatment data would be invaluable both with respect to the score, and as within a broader epidemiological scope. An analysis of this subgroup would not only increase the validity of the presented score, but also serve as clinical evidence on whether ACE2 inhibitors affect outcomes and COVID-19 phenotypes.

critical care

Letter to the editor: The role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in developing a COVID-19 comorbidity-based host risk score