Serum ACE2, Angiotensin II, and Aldosterone Levels Are Unchanged in Patients With COVID-19

Rieder, Marina; Wirth, Luisa; Pollmeier, Luisa; Jeserich, Maren; Goller, Isabella; Baldus, Niklas; Schmid, Bonaventura; Busch, Hans-Joerg; Hofmann, Maike; Kern, Winfried V.; Bode, Christoph; Duerschmied, Daniel; Lother, Achim

doi:10.1093/ajh/hpaa169

Cited by 95 publications

(103 citation statements)

References 16 publications

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“…Baseline ACE2 levels did not show statistically significant differences between COVID-19 positive and negative patients, which is in line with the results of a recent study with a much smaller sample size. 39 The associations between high plasma levels of ACE2 and worse WHOmax category during 28 days were more pronounced in COVID-19 positive patients compared with COVID-19 negative patients but the difference was not significant in the two-way ANOVA analysis. It is therefore not possible with this dataset to conclude whether differences in ACE2 levels are specifically associated with disease outcome in patients with COVID-19 positive disease only.…”

Section: Discussionmentioning

confidence: 81%

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Kragstrup

Singh

Grundberg

et al. 2021

Preprint

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). COVID-19 is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe hyperinflammatory syndrome and death. Methods This study used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO) COVID-19 outcomes scale. The samples were run on the Olink Explore 1536 platform which includes measurement of the ACE2 protein. Findings High baseline levels of ACE2 in plasma from COVID-19 patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of ACE2 in plasma from COVID-19 patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of ACE2 in plasma from COVID-19 patients with hypertension were significantly higher compared to patients without hypertension (P = 0.0045). The plasma ACE2 levels were also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma ACE2 levels comparing patients with or without pre-existing lung disease, diabetes, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of ACE2 and worse WHOmax category during 28 days were more pronounced in COVID-19 positive patients compared with COVID-19 negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 levels could be a link between severe COVID-19 disease and its risk factors, namely hypertension, pre-existing heart disease and pre-existing kidney disease. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma ACE2 and ACE1 activity. This is interesting because ACE1 (serum ACE) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in COVID-19.

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Section: Discussionmentioning

confidence: 81%

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Kragstrup

Singh

Grundberg

et al. 2021

Preprint

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“…However, the role of sACE2 levels as a potential risk marker of severe COVID-19 is controversial (Rieder et al, 2020 ; Rojas et al, 2020 ). sACE2 levels are higher in males, increase with age and are associated with BMI and the metabolic syndrome (Kornilov et al, 2020 ; Sama et al, 2020 ; Sward et al, 2020 ), which are both described as risk factors for severe COVID-19 (Grasselli et al, 2020 ; Suleyman et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Serum Renin Levels Increase With Age in Boys Resulting in Higher Renin Levels in Young Men Compared to Young Women, and Soluble Angiotensin-Converting Enzyme 2 Correlates With Renin and Body Mass Index

et al. 2021

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Background: Age, sex, and body constitution may affect the shedding of membrane bound angiotensin-converting enzyme 2 (mACE2) and lead to a relative mACE2 deficiency. However, it is unclear if differences, reflected by serum renin levels, exist in the basal renin-angiotensin-system (RAS) between children and adults, boys, and girls as well as young women and young men. Furthermore, it remains to be investigated if renin and soluble ACE2 (sACE2) levels are correlated with body mass index (BMI) in children and young adults. The aim of this observational study was to assess age-and sex differences in serum renin, and the relationship between renin, soluble angiotensin-converting enzyme 2, and body mass index in a prospectively followed population-based cohort of children which were followed into young adulthood.Study Design: We analyzed renin and sACE2 in serum in a prospectively followed population-based cohort at 9.9 (0.6) [mean (SD)] (n = 173), 11.7 (0.6) (n = 156), 14.8 (0.8) (n = 149), 18.8 (0.3) (n = 93), and 23.5 (0.7) (n = 152) years of age. Height (cm) and weight (kg) was measured and body mass index (BMI) was calculated as weight (kg)/height (m)2. Sex-related differences in renin levels were calculated using analysis of covariance, adjusted for age. Correlations were assessed by calculating the correlation coefficient (R2) using a multivariable linear mixed model.Results: Both sexes had low renin levels up to 12 years of age. Thereafter renin levels increased more in boys than in girls. Males from the age of 15 had significantly higher levels than females (p < 0.001). There was a positive linear relationship between renin and sACE2 levels in male and female subjects (p < 0.001), and between sACE2 levels and BMI in males (p < 0.001).Conclusion: Renin levels increase with age, are higher in men than in women since around puberty, and are correlated with sACE2 levels. Furthermore, sACE2 levels are correlated with body mass index in males. These findings indicate that high renin levels in males and females and a high BMI in males may activate pathways which increase the shedding of mACE2, with possible implications for the risk of severe coronavirus disease 2019.

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“…AngII concentrations could be markedly reduced, whereas protective Ang1–7 profoundly increased by injecting human recombinant soluble ACE2 in a recent study, leading to a reduction of inflammatory cytokines and improved clinical condition [ 173 ]. In contrast, two studies reported no changes in plasma angiotensin II levels in SARS-CoV-2 infected patients [ 176 , 177 ]. However, patients in both studies did not suffer severe COVID-19 compared to the Wuhan cohort, where all patients suffered pneumonia and/or ARDS [ 172 ].…”

Section: Summary Of Study Findings: Tras and Its Tole In Human Tismentioning

confidence: 99%

The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

Saravi

Lang

et al. 2021

Cells

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Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1–7/MasReceptor axis. Numerous studies reported the positive effects of pathologic tRAS pathway inhibition and protective tRAS pathway stimulation on the treatment of cardiovascular, inflammatory, and autoimmune disease and the progression of neuropathic pain. Cell senescence and aging are known to be related to RAS pathways. Further, this system directly interacts with SARS-CoV 2 and seems to be an important target of interest in the COVID-19 pandemic. This review focuses on the involvement of tRAS in the progression of the mentioned diseases from an interdisciplinary clinical perspective and highlights therapeutic strategies that might be of major clinical importance in the future.

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Serum ACE2, Angiotensin II, and Aldosterone Levels Are Unchanged in Patients With COVID-19

Cited by 95 publications

References 16 publications

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Serum Renin Levels Increase With Age in Boys Resulting in Higher Renin Levels in Young Men Compared to Young Women, and Soluble Angiotensin-Converting Enzyme 2 Correlates With Renin and Body Mass Index

The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

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