Is the ACE2 Overexpression a Risk Factor for COVID-19 Infection?

Gracia‐Ramos, Abraham Edgar

doi:10.1016/j.arcmed.2020.03.011

Cited by 49 publications

(47 citation statements)

References 10 publications

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“…Conversely, chronic diseases, such as hypertension and diabetes, and some medications may increase the level of ACE 2 expression in different tissues 41,42 . This last condition is believed to facilitate the internalization of SARS‐CoV‐2 into host cells in several systems, thus, contributing to worsen the prognosis in COVID‐19, 41,42 even if this emergent issue remains still debated 43 . In animal model, ACE 2 expression in pulmonary and bronchial epithelium dramatically decreased with aging more in male rats than female 44 .…”

Section: Resultsmentioning

confidence: 99%

Worse progression of COVID‐19 in men: Is testosterone a key factor?

et al. 2020

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Background The novel severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) disease 2019 (COVID‐19) seems to have a worse clinical course among infected men compared with women, thus highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context. Objective To overview on possible mechanisms by which serum T levels could affect the progression of COVID‐19 in men. Methods Authors searched PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, Google, and institutional websites for medical subject headings terms and free text words referred to “SARS‐CoV‐2,” “COVID‐19,” “testosterone,” “male hypogonadism,” “gender” “immune system,” “obesity,” “thrombosis” until May 19th 2020. Results T, co‐regulating the expression of angiotensin‐converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS‐CoV‐2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. Discussion and conclusion T in comparison to estrogen may predispose men to a widespread COVID‐19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially elderly men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Worse progression of COVID‐19 in men: Is testosterone a key factor?

et al. 2020

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“…There was some initial controversy regarding the need to stop RAS blockade, which is widely prescribed to CKD patients. ACE2 expression is increased in diabetes and treatment with ACE inhibitors and angiotensin II receptor blockers(ARBs) increases ACE2 expression [ 56 , 57 ]. It was thus hypothesized that RAS blockade–induced ACE2 expression may facilitate COVID-19 infection [ 56 ].…”

Section: Prevention and Treatment Of Covid-19 In Ckdmentioning

confidence: 99%

Coronavirus disease 2019 in chronic kidney disease

D’Marco

Puchades

Romero-Parra

et al. 2020

Clinical Kidney Journal

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The clinical spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic infection to severe pneumonia with respiratory failure and even death. More severe cases with higher mortality have been reported in older patients and in those with chronic illness such as hypertension, diabetes or cardiovascular diseases. In this regard, patients with chronic kidney disease (CKD) have a higher rate of all-type infections and cardiovascular disease than the general population. A markedly altered immune system and immunosuppressed state may predispose CKD patients to infectious complications. Likewise, they have a state of chronic systemic inflammation that may increase their morbidity and mortality. In this review we discuss the chronic immunologic changes observed in CKD patients, the risk of COVID-19 infections and the clinical implications for and specific COVID-19 therapy in CKD patients. Indeed, the risk for severe COVID-19 is 3-fold higher in CKD than in non-CKD patients; CKD is 12-fold more frequent in intensive care unit than in non-hospitalized COVID-19 patients, and this ratio is higher than for diabetes or cardiovascular disease; and acute COVID-19 mortality is 15–25% for haemodialysis patients even when not developing pneumonia.

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“…However, patients with these comorbidities are likely to be treated with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), which could upregulate the expression of ACE2 receptor in animal studies [7,8]. Since ACE2 is the functional receptor for coronavirus entry into cells [9], there is concern regarding an increased risk of COVID-19 infection among those who use ACEI/ARB treatment [10]. Conversely, there is evidence that exogenous ACE2 supplementation can reduce inflammation and increase oxygenation in animal models of acute respiratory distress syndrome (ARDS) [11].…”

Section: Introductionmentioning

confidence: 99%

ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis

Zhang

Pan

et al. 2020

Pharmacological Research

156

171

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The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29−0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.

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Is the ACE2 Overexpression a Risk Factor for COVID-19 Infection?

Cited by 49 publications

References 10 publications

Worse progression of COVID‐19 in men: Is testosterone a key factor?

Worse progression of COVID‐19 in men: Is testosterone a key factor?

Coronavirus disease 2019 in chronic kidney disease

ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis

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