Renin–angiotensin system dysregulation in critically ill patients with acute respiratory distress syndrome due to COVID-19: a preliminary report

Eleuteri, Davide; Montini, Luca; Cutuli, Salvatore Lucio; Rossi, Cristina; Alcaro, Francesca; Antonelli, Massimo

doi:10.1186/s13054-021-03507-7

Cited by 15 publications

(24 citation statements)

References 6 publications

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“…This report has demonstrated higher sFlt-1 levels in pregnant women with COVID-19 severe pneumonia. Other studies have reported lower plasma ACE-2 levels in non-survivors than in critically ill patients that have survived COVID-19 [30], however, our study has failed to demonstrate a difference in this parameter between those with critical illness and non-critical illness. We have found lower plasma levels of ANG-II in pregnant women with severe pneumonia by COVID-19.…”

Section: Comparison With Existing Literaturecontrasting

confidence: 97%

Novel Ratio Soluble Fms-like Tyrosine Kinase-1/Angiotensin-II (sFlt-1/ANG-II) in Pregnant Women Is Associated with Critical Illness in COVID-19

Sosa

Martínez-Portilla

Torres-Torres

et al. 2021

Viruses

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Background: In healthy pregnancies, components of the Renin-Angiotensin system (RAS) are present in the placental villi and contribute to invasion, migration, and angiogenesis. At the same time, soluble fms-like tyrosine kinase 1 (sFlt-1) production is induced after binding of ANG-II to its receptor (AT-1R) in response to hypoxia. As RAS plays an essential role in the pathogenesis of COVID-19, we hypothesized that angiogenic marker (sFlt-1) and RAS components (ANG-II and ACE-2) may be related to adverse outcomes in pregnant women with COVID-19; Methods: Prospective cohort study. Primary outcome was severe pneumonia. Secondary outcomes were ICU admission, intubation, sepsis, and death. Spearman’s Rho test was used to analyze the correlation between sFlt-1 and ANG-II levels. The sFlt-1/ANG-II ratio was determined and the association with each adverse outcome was explored by logistic regression analysis and the prediction was assessed using receiver-operating-curve (ROC); Results: Among 80 pregnant women with COVID-19, the sFlt-1/ANG-II ratio was associated with an increased probability of severe pneumonia (odds ratio [OR]: 1.31; p = 0.003), ICU admission (OR: 1.05; p = 0.007); intubation (OR: 1.09; p = 0.008); sepsis (OR: 1.04; p = 0.008); and death (OR: 1.04; p = 0.018); Conclusion: sFlt-1/ANG-II ratio is a good predictor of adverse events such as pneumonia, ICU admission, intubation, sepsis, and death in pregnant women with COVID-19.

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Section: Comparison With Existing Literaturecontrasting

confidence: 97%

Novel Ratio Soluble Fms-like Tyrosine Kinase-1/Angiotensin-II (sFlt-1/ANG-II) in Pregnant Women Is Associated with Critical Illness in COVID-19

Sosa

Martínez-Portilla

Torres-Torres

et al. 2021

Viruses

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“…These observations suggest that severe COVID-19 is associated with global RAS dysregulation but not simply with a skewed balance in favor of ACE1 activity. This might reflect a global reduction of ACE1 and ACE2 expression in the damaged lung [103,104], a hypothesis which will deserve confirmation.…”

mentioning

confidence: 91%

“…The role of ACE1/ACE2 imbalance and ATII signaling in COVID-19 remains, however, to be clarified. Indeed, while early data indicated a positive correlation between circulating ATII levels and the severity of the disease [102], two recent studies reported contrasting results with lower circulating ATII in non-survivors [103,104]. These observations suggest that severe COVID-19 is associated with global RAS dysregulation but not simply with a skewed balance in favor of ACE1 activity.…”

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confidence: 98%

The Right Ventricle in COVID-19

Bonnemain

Ltaief

Liaudet

2021

JCM

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Infection with the novel severe acute respiratory coronavirus-2 (SARS-CoV2) results in COVID-19, a disease primarily affecting the respiratory system to provoke a spectrum of clinical manifestations, the most severe being acute respiratory distress syndrome (ARDS). A significant proportion of COVID-19 patients also develop various cardiac complications, among which dysfunction of the right ventricle (RV) appears particularly common, especially in severe forms of the disease, and which is associated with a dismal prognosis. Echocardiographic studies indeed reveal right ventricular dysfunction in up to 40% of patients, a proportion even greater when the RV is explored with strain imaging echocardiography. The pathophysiological mechanisms of RV dysfunction in COVID-19 include processes increasing the pulmonary vascular hydraulic load and others reducing RV contractility, which precipitate the acute uncoupling of the RV with the pulmonary circulation. Understanding these mechanisms provides the fundamental basis for the adequate therapeutic management of RV dysfunction, which incorporates protective mechanical ventilation, the prevention and treatment of pulmonary vasoconstriction and thrombotic complications, as well as the appropriate management of RV preload and contractility. This comprehensive review provides a detailed update of the evidence of RV dysfunction in COVID-19, its pathophysiological mechanisms, and its therapy.

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“…The meta-analysis that we carried out in the previous section has shed some light on these questions to a certain extent, but many points remain obscure. Indeed, the experimental and clinical data that we collected from the literature about e.g., the levels of proteins and peptides involved in RAS and the activity of the enzymes, partially disagree [77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92].…”

Section: Discussionmentioning

confidence: 99%

“…The data collected shows a slightly increased average level of AngII in COVID-19 patients with respect to controls (Table 1). More precisely, roughly half of the studies observe a decrease in AngII levels [80,84,85] and the others, an increase [87,82,81] (Figure 3b). Instead, one would naively expect a general decrease of AngII level, given that ACE2 shows upregulated activity and cleaves AngII.…”

Section: Meta-analysis On Ras Components In Covid-19mentioning

confidence: 94%

Quantifying renin-angiotensin-system alterations in COVID-19

Pucci

Annoni

Santos

et al. 2021

Preprint

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The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes. One of its key components, the angiotensin-converting enzyme 2, has been identified as the entry point of the SARS-CoV-2 virus into the host cells, so many studies have been devoted to study RAS dysregulation in COVID-19. Here we discuss the alterations of the regulatory RAS axes due to SARS-CoV-2 infection on the basis of a series of recent clinical and experimental analyzes, which, for example, quantify the levels and activity of RAS components, in order to disentangle the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. Finally, we discussed the effects of some RAS-targeting drugs, and how they could potentially contribute to restore the normal RAS functionality and minimize COVID-19 severity.

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Renin–angiotensin system dysregulation in critically ill patients with acute respiratory distress syndrome due to COVID-19: a preliminary report

Cited by 15 publications

References 6 publications

Novel Ratio Soluble Fms-like Tyrosine Kinase-1/Angiotensin-II (sFlt-1/ANG-II) in Pregnant Women Is Associated with Critical Illness in COVID-19

Novel Ratio Soluble Fms-like Tyrosine Kinase-1/Angiotensin-II (sFlt-1/ANG-II) in Pregnant Women Is Associated with Critical Illness in COVID-19

The Right Ventricle in COVID-19

Quantifying renin-angiotensin-system alterations in COVID-19

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