Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

Kragstrup, Tue Wenzel; Singh, Helene Søgaard; Grundberg, Ida; Nielsen, Ane Langkilde Lauesen; Rivellese, Felice; Mehta, Arnav; Goldberg, Marcia B.; Filbin, Michael R.; Qvist, Per; Bibby, Bo Martin

doi:10.1371/journal.pone.0252799

Cited by 97 publications

(103 citation statements)

References 53 publications

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“…Soluble ACE2 on the other side could reflect the cleavage of membrane-bound ACE2 during the SARS-CoV-2 entry and lysis of ACE2-expressing cells. High levels of plasma ACE2 is proposed to indicate poor outcome in critically ill patients [ 19 , 20 ]. The moderate disease course was different in our patients, in whom elevated ACE2 levels were seen in association with good outcomes without any ARDS, serious complication or mortality.…”

Section: Discussionmentioning

confidence: 99%

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism

Bolay

Karadaş²,

Öztürk³

et al. 2021

J Headache Pain

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Background and aim Pathogenesis of COVID-19 -related headache is unknown, though the induction of the trigeminal neurons through inflammation is proposed. We aimed to investigate key systemic circulating inflammatory molecules and their clinical relations in COVID-19 patients with headache. Methods This cross-sectional study enrolled 88 COVID-19 patients, hospitalized on a regular ward during the second wave of the pandemic. Clinical characteristics of COVID-19 patients were recorded, and laboratory tests were studied. Results The mean ages of 48 COVID-19 patients with headache (47.71 ± 10.8) and 40 COVID-19 patients without headache (45.70 ± 12.72) were comparable. COVID-19 patients suffered from headache had significantly higher serum levels of HMGB1, NLRP3, ACE2, and IL-6 than COVID-19 patients without headache, whereas CGRP and IL-10 levels were similar in the groups. Angiotensin II level was significantly decreased in the headache group. COVID-19 patients with headache showed an increased frequency of pulmonary involvement and increased D- dimer levels. Furthermore, COVID-19 was more frequently associated with weight loss, nausea, and diarrhea in patients with headache. Serum NLRP3 levels were correlated with headache duration and hospital stay, while headache response to paracetamol was negatively correlated with HMGB1 and positively associated with IL-10 levels. Conclusion Stronger inflammatory response is associated with headache in hospitalized COVID-19 patients with moderate disease severity. Increased levels of the circulating inflammatory and/or nociceptive molecules like HMGB1, NLRP3, and IL-6 may play a role in the potential induction of the trigeminal system and manifestation of headache secondary to SARS-CoV-2 infection.

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Section: Discussionmentioning

confidence: 99%

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism

Bolay

Karadaş²,

Öztürk³

et al. 2021

J Headache Pain

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“…We review here recent data about measurements of RAS components in COVID-19. For that purpose, we manually collected and screened a series of clinical and experimental results from [79][80][81][82][83][84][85][86][87][88][89][90][91][92][93][94], listed in Supplementary Table S1. The individuals enrolled in these studies were classified into two or three classes: COVID-19 patients or severe and moderate COVID-19 patients, and controls or asymptomatic patients.…”

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

confidence: 99%

Quantifying Renin-Angiotensin-System Alterations in COVID-19

Pucci

Annoni

Santos

et al. 2021

Cells

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The renin-angiotensin system (RAS) plays a pivotal role in a wide series of physiological processes, among which inflammation and blood pressure regulation. 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, and therefore a lot of research has 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 investigations and experimental analyzes quantifying, e.g., the levels and activity of RAS components. We performed a comprehensive meta-analysis of these data in view of disentangling the links between the impaired RAS functioning and the pathophysiological characteristics of COVID-19. We also review the effects of several RAS-targeting drugs and how they could potentially help restore the normal RAS functionality and minimize the COVID-19 severity. Finally, we discuss the conflicting evidence found in the literature and the open questions on RAS dysregulation in SARS-CoV-2 infection whose resolution would improve our understanding of COVID-19.

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“…Interestingly, once released, the ectodomain of ACE2 keeps the catalytic activity which is able to cleave circulating vasoactive peptides [ 7 , 11 ] and, in the context of SARS-CoV-2 infection, might also significantly influence viral spread and pathogenesis, either by limiting new viral infections acting as a soluble decoy or, alternatively, limiting local inflammation due to its tissue protective function. In this sense, elevated circulating ACE2 levels have been reported in different cohorts of COVID-19 patients, suggesting a relation between clinical course and ACE2 levels either in acute or long-term disease [ 12 , 13 , 14 , 15 ], although data needs further validation.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients

Gutiérrez-Chamorro

Riveira-Muñoz

Barrios

et al. 2021

Viruses

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Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-COV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with ACE2 gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.

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Plasma ACE2 predicts outcome of COVID-19 in hospitalized patients

Cited by 97 publications

References 53 publications

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism

HMGB1, NLRP3, IL-6 and ACE2 levels are elevated in COVID-19 with headache: a window to the infection-related headache mechanism

Quantifying Renin-Angiotensin-System Alterations in COVID-19

SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients

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