Vasoactive Peptides: Role in COVID-19 Pathogenesis and Potential Use as Biomarkers and Therapeutic Targets

Khodabakhsh, Pariya; Taei, Afsaneh Asgari; Mohseni, Moein; Zanjanbar, Dorsa Bahrami; Khalili, Hasti; Masoumi, Kimia; Shirazi, Alireza Haji Abbas; Dargahi, Leila

doi:10.1016/j.arcmed.2021.05.007

Cited by 12 publications

(18 citation statements)

References 91 publications

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“…Even if CGRP involvement in lung physiology has been extensively studied [ 5 , 30 , 31 , 32 ], its potential role in COVID-19 is poorly understood. To date, only a few studies have focused on this topic [ 15 , 33 ], with no possibility of obtaining conclusive results.…”

Section: Discussionmentioning

confidence: 99%

“…Some patients develop a hyperinflammatory reaction to the infection, the so-called cytokine storm, but little information is available about adopting surely effective approaches to prevent it [ 4 ]. Although many inflammatory mediators or vasoactive peptides (interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-α), angiotensin II (Ang II), vasoactive intestinal peptide (VIP), and endothelin 1 (ET-1)) have been proposed as biomarkers of disease evolution, so far, it is difficult to have a clear prognosis for patients or indications in order for a more proper pharmacological strategy to be promptly adopted [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients

Rizzi

Tonello

Morani

et al. 2022

Viruses

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SARS-CoV-2 is the etiological agent of COVID-19, an extremely heterogenous disease that can cause severe respiratory failure and critical illness. To date, reliable biomarkers allowing for early patient stratification according to disease severity are still lacking. Calcitonin gene-related peptide (CGRP) is a vasoactive neuropeptide involved in lung pathophysiology and immune modulation and is poorly investigated in the COVID-19 context. In this observational, prospective cohort study, we investigated the correlation between CGRP and clinical disease evolution in hospitalized moderate to severe COVID-19 patients. Between January and May 2021 (Italian third pandemic wave), 135 consecutive SARS-CoV-2 patients were diagnosed as being eligible for the study. Plasma CGRP level evaluation and routine laboratory tests were performed on blood samples collected at baseline and after 7 days of hospitalization. At baseline, the majority our patients had a moderate to severe clinical presentation, and higher plasma CGRP levels predicted a higher risk of in-hospital negative evolution (odds-ratio OR 2.84 [IQR 1.07–7.51]) and were correlated with pulmonary intravascular coagulopathy (OR 2.92 [IQR 1.19–7.17]). Finally, plasma CGRP levels were also correlated with plasma IP10 levels. Our data support a possible crosstalk between the lung and the neuroimmune axis, highlighting a crucial role for plasma CGRP in sustaining COVID-19-related hyperinflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients

Rizzi

Tonello

Morani

et al. 2022

Viruses

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“…8,9 A recent study showed that vasoactive peptide is expected to be a biomarker for the diagnosis of Corona Virus Disease 2019 (COVID-19). 10 The workflows of peptidomics and proteomics have great similarities. The biggest difference is that proteomics samples need to be digested before mass spectrometry, while peptide samples are analyzed directly after removing the intact protein (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Application of peptide biomarkers in life analysis based on liquid chromatography–mass spectrometry technology

Han

Cong

et al. 2022

BioFactors

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Biomedicine is developing rapidly in the 21st century. Among them, the qualitative and quantitative analysis of peptide biomarkers is of considerable importance for the diagnosis and therapy of diseases and the quality evaluation of drugs and food. The identification and quantitative analysis of peptides have been going on for decades. Traditionally, immunoassays or biological assays are generally used to quantify peptides in biological matrices. However, the selectivity and sensitivity of these methods cannot meet the requirements of the application. The separation and analysis technique of liquid chromatography-mass spectrometry (LC-MS) supplies a reliable alternative. In contrast to immunoassays, LC-MS methods are capable of providing the analytical prowess necessary to satisfy the demands of peptide biomarker research in the life sciences arena. This review article provides a historical account of the in-roads made by LC-MS technology for the detection of peptide biomarkers in the past 10 years, with the focus on the qualification/quantification developments and their applications.

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“…On the other hand, the VPAC 2 receptor was always found in the plasma membrane location. From a translational point of view, the VIP axis has an important potential in the control of inflammation and the modulation of several autoimmune diseases, but it could also be used as a biomarker for personalized treatment in autoimmune diseases such as rheumatoid arthritis [17,[26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Human CD4+CD45RA+ T Cells Behavior after In Vitro Activation: Modulatory Role of Vasoactive Intestinal Peptide

Villanueva‐Romero

Cabrera-Martín

Álvarez-Corrales

et al. 2022

IJMS

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Naїve CD4+ T cells, which suffer different polarizing signals during T cell receptor activation, are responsible for an adequate immune response. In this study, we aimed to evaluate the behavior of human CD4+CD45RA+ T cells after in vitro activation by anti-CD3/CD28 bead stimulation for 14 days. We also wanted to check the role of the VIP system during this process. The metabolic biomarker Glut1 was increased, pointing to an increase in glucose requirement whereas Hif-1α expression was higher in resting than in activated cells. Expression of Th1 markers increased at the beginning of activation, whereas Th17-associated biomarkers augmented after that, showing a pathogenic Th17 profile with a possible plasticity to Th17/1. Foxp3 mRNA expression augmented from day 4, but no parallel increases were observed in IL-10, IL-2, or TGFβ mRNA expression, meaning that these potential differentiated Treg could not be functional. Both VIP receptors were located on the plasma membrane, and expression of VPAC2 receptor increased significantly with respect to the VPAC1 receptor from day 4 of CD4+CD45RA+ T activation, pointing to a shift in VPAC receptors. VIP decreased IFNγ and IL-23R expression during the activation, suggesting a feasible modulation of Th17/1 plasticity and Th17 stabilization through both VPAC receptors. These novel results show that, without polarizing conditions, CD4+CD45RA+ T cells differentiate mainly to a pathogenic Th17 subset and an unpaired Treg subset after several days of activation. Moreover, they confirm the important immunomodulatory role of VIP, also on naїve Th cells, stressing the importance of this neuropeptide on lymphocyte responses in different pathological or non-pathological situations.

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Vasoactive Peptides: Role in COVID-19 Pathogenesis and Potential Use as Biomarkers and Therapeutic Targets

Cited by 12 publications

References 91 publications

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients

CGRP Plasma Levels Correlate with the Clinical Evolution and Prognosis of Hospitalized Acute COVID-19 Patients

Application of peptide biomarkers in life analysis based on liquid chromatography–mass spectrometry technology

Human CD4+CD45RA+ T Cells Behavior after In Vitro Activation: Modulatory Role of Vasoactive Intestinal Peptide

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