Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?
By L. Fang, G. Karakiulakis, M. Roth. The Lancet Respiratory Medicine, 2020
2,671 citations recorded by the source corpus.
The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues were cerebro vascular diseases (22%) and diabetes (22%). Another study included 1099 patients with confirmed COVID-19, of whom 173 had severe disease with comorbidities of hypertension (23·7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%). In a third study, of 140 patients who were admitted to hospital with COVID-19, 30% had hypertension and 12% had diabetes. Notably, the most frequent comorbidities reported in these three studies of patients with COVID-19 are often treated with angiotensin-converting enzyme (ACE) inhibitors; however, treatment was not assessed in either study. Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARSCoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs). Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2. ACE2 can also be increased by thiazolidinediones and ibuprofen. These data suggest that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19. If this hypothesis were to be confirmed, it could lead to a conflict regarding treatment because ACE2 reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes, and hypertension. A further aspect that should be investigated is the genetic predisposition for an increased risk of SARS-CoV-2 infection, which might be due to ACE2 polymorphisms that have been linked to diabetes mellitus, cerebral stroke, and hypertension, specifically in Asian populations. Summarising this information, the sensitivity of an individual might result from a combination of both therapy and ACE2 polymorphism. We suggest that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs. Based on a PubMed search on Feb 28, 2020, we did not find any evidence to suggest that antihypertensive calcium channel blockers increased ACE2 expression or activity, therefore these could be a suitable alternative treatment in these patients. We declare no competing interests.
Subfields: Cardiology and Cardiovascular Medicine, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/cfb505b2a83896fc14764ca71e5df290a63a730f
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Citations in the corpus
- Rapid implementation of mobile technology for real-time epidemiology of COVID-19 (2020, background): “incidence and outcomes vary according to age, sex, race/ethnicity, and underlying health status, with inconsistent evidence suggesting that commonly used medications such as angiotensin-converting enzyme (ACE) inhibitors, thiazolidinediones (TZD), and ibuprofen may alter the natural disease course (”
- Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions (2020, neutral): “increased expression of hACE2 on lung epithelial cells, some authors have postulated a connection between these points [12].”
- A Comprehensive Review of the COVID-19 Pandemic and the Role of IoT, Drones, AI, Blockchain, and 5G in Managing its Impact (2020, background): “In the months following the COVID-19 outbreak, several papers examining different aspects of the COVID-19 have been published [16]–[22].”
- Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19 (2020, background): “There are also concerns that treatment with ACEIs/ARBs may facilitate infection and increase the risk of developing severe and fatal COVID-19 by increasing ACE2 expression levels in target organs [106].”
- COVID-19 and comorbidities: Deleterious impact on infected patients (2020, background): “upregulate expression of the ACE-2 receptor, thereby leading to increased susceptibility to SARS-CoV-2 infection [25].”
- Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression (2020, neutral): “pneumocytes and consequently cause severe and fatal infection [42].”
- Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19 (2020, background): “8 Further fueling these concerns is the observation that hypertension may be associated with an increased risk of death among patients with Covid-19.”
- Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 (2020, background): “6, 7 Others have suggested that ACE inhibitors may counter the antiinflammatory effects of ACE2.”
- The pivotal link between ACE2 deficiency and SARS-CoV-2 infection (2020, neutral): “[76] [77] [78] [79] [80] [81] [82] [83] [84] Several Scientific Societies and various experts in this area expressed the position that discontinuation of these drugs is not justified by evidence and could be dangerous.”
- Practical recommendations for the management of diabetes in patients with COVID-19 (2020, background): “13 However, as SARS-CoV-2 might impair the protective ACE2/Mas receptor pathway and increase deleterious angiotensin-2 activity, the use of ACE inhibitors and angiotensin 2 receptor blockers could protect against severe lung injury following infection.”
- Mortality-related risk factors of COVID-19: a systematic review and meta-analysis of 42 studies and 423,117 patients (2021, background): “Diabetes also contributes to more severe COVID-19 and higher rates of mortality [81].”
- Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations (2020, positive): “Since CCB has no effect on ACE2 expression, some researchers have proposed its preferable use in patients with COVID-19 and hypertension [80] .”