Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients

Anders Holt; Ikram Mizrak; Morten Lamberts; Per Lav Madsen

Anders Holt, Ikram Mizrak, Morten Lamberts, Per Lav Madsen

Journal of Hypertension, doi:10.1097/hjh.0000000000002515

OVID-19, the disease associated with SARS-CoV-2 infection, is in some 20% of acutely affected patients associated with respiratory distress syndrome (ARDS) often necessitating respirator treatment and associated with a high mortality [1] [2] [3] . Epidemics in Wuhan in China and Lombardy in Italy have been devastating, and SARS-CoV-2 has developed into a pandemic necessitating urgent worldwide co-operation. Until effective treatment of COVID-19 including a useful vaccination against SARS-CoV-2 is found, it is important to seek ways of limiting or avoiding ARDS. Virus-related ARDS is initiated from a high level of angiotensin II (Ang-II) via the type 1 receptor pathway [4], and Ang-II has already been demonstrated to be high in COVID-19 and linearly associated with lung injury [5] . Inhibitors of the renin-angiotensin system (RASi), cornerstones of treatment of patients with hypertension and heart failure, have attracted attention as they may in theory influence the Ang-II level in COVID-19 and thereby the risk of ARDS [4, 6] . In short, Ang-II activity is influenced by the balance of Ang-converting enzyme (ACE) and ACE2 receptor activity. The activity of ACE2 normally lowers the level of Ang-II, but SARS-CoV-2 virus binds to ACE2 receptors, lower their activity and hence increase Ang-II activity [1] . While RASi lower Ang-II levels, and may in this respect be helpful, chronic RASi treatment may on the other hand also increase pulmonary ACE2-receptor numbers hence providing a possible higher SARS-CoV-2 viral load. As suggested from animal experiments, chronic treatment with RASi can therefore, in theory, both increase and lower the risk of ARDS in SARS-CoV-2-infected patients. Studies early listed heart disease, hypertension, and diabetes as risk factors for ARDS [1-3], but unfortunately medication has not yet been reported on, and clinical data on the relative importance of RASi for outcome in COVID-19 are now urgently needed. Approved by the Danish Patient Safety Authority and the Danish Data Protection Agency, we related medication to outcome in all SARS-CoV-2 PCR positive patients, who,

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