CGRP Receptor Antagonism in COVID-19: Potential Cardiopulmonary Adverse Effects

Skaria, Tom; Wälchli, Thomas; Vogel, Johannes

doi:10.1016/j.molmed.2020.10.005

Cited by 16 publications

(13 citation statements)

References 16 publications

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“…After this article was accepted, we learnt that the US Food and Drug Administration (FDA) had authorized a clinical trial sponsored by Biohaven Pharmaceuticals, Inc. where COVID-19 patients are to be treated with CGRP antagonists [ 44 ]. Given our results, and in agreement with Skaria et al [ 45 ], we believe that this approach could further deteriorate the respiratory capacity of the patients. If this trial is finally carried out, we recommend a close monitoring of the patients to avoid potential negative consequences.…”

Section: Note Added In Presssupporting

confidence: 93%

Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients

Ochoa-Callejero

Garcı́a-Sanmartı́n

Villoslada-Blanco

et al. 2021

Journal of the Endocrine Society

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Background To better understand the biology of COVID-19, we have explored the behavior of calcitonin gene-related peptide (CGRP), an angiogenic, vasodilating, and immune modulating peptide, in severe acute respiratory syndrome coronavirus 2 positive patients. Methods Levels of CGRP in the serum of 57 COVID-19 patients (24 asymptomatic, 23 hospitalized in the general ward, and 10 admitted to the intensive care unit) and healthy donors (n = 24) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, to better understand the physiological consequences of the observed variations, we investigated by immunofluorescence the distribution of receptor activity modifying protein 1 (RAMP1), one of the components of the CGRP receptor, in autopsy lung specimens. Results CGRP levels were greatly decreased in COVID-19 patients (P < 0.001) when compared to controls, and there were no significant differences due to disease severity, sex, age, or comorbidities. We found that COVID-19 patients treated with proton pump inhibitors had lower levels of CGRP than other patients not taking this treatment (P = 0.001). RAMP1 immunoreactivity was found in smooth muscle cells of large blood vessels and the bronchial tree and in the airways´ epithelium. In COVID-19 samples, RAMP1 was also found in proliferating type II pneumocytes, a common finding in these patients. Conclusions The lower levels of CGRP should negatively impact the respiratory physiology of COVID-19 patients due to vasoconstriction, improper angiogenesis, less epithelial repair, and faulty immune response. Therefore, restoring CGRP levels in these patients may represent a novel therapeutic approach for COVID-19.

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Section: Note Added In Presssupporting

confidence: 93%

Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients

Ochoa-Callejero

Garcı́a-Sanmartı́n

Villoslada-Blanco

et al. 2021

Journal of the Endocrine Society

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“…Recent research on CGRP has led to an expansion of potential target therapies that include chronic visceral pain, the enteric nervous system, ischemic cardiovascular events, opioid tolerance and withdrawal, and lung inflammation from COVID-19 infections [6][7][8]. Many of these treatment avenues are still undergoing clinical trials and thus further research is warranted.…”

Section: Introductionmentioning

confidence: 99%

A Pharmacological Review of Calcitonin Gene-Related Peptide Biologics and Future Use for Chronic Pain

Cooper¹,

Laidig²,

Sappington³

et al. 2023

Cureus

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Calcitonin gene-related peptide (CGRP) antagonist medications have become the mainstay of acute and chronic migraine management in the outpatient setting and look to become more widely utilized by clinicians once the medications become available in generic form. However, their role in practice has remained limited to the treatment of migraines despite the ubiquitous presence of the molecule throughout the body. The literature surrounding expansion of the utility of these medications is limited; however, there have been several promising publications, and further studies are in the process to quantify their utility in the treatment of other pain-related disorders. This is a qualitative review of the current literature surrounding CGRP, particularly in relation to the treatment of non-migraine pain conditions, and looks to suggest potential utility in the field of chronic pain.

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“…10 Not only is CGRP released in the nasal mucosa following the increase in TNF-α during COVID-19 infection, but it is also released from the dura mater, thus increasing the meningeal blood flow. 11,54 Therefore, the cytokines will induce a secondary activation of meningeal nociceptors, causing headache. 11 A CGRP-induced headache caused by COVID-19 may resemble migraine due to the common pathophysiology of CGRP.…”

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confidence: 99%

The Pathophysiological Relationship Between Migraine and SARS-CoV-2 Infection: A Comprehensive Literature Review

Elkurwi

2022

EMJ

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People with migraine, and individuals with other neurological conditions, have suffered in multiple aspects during the COVID-19 pandemic. This paper will discuss the factors that impacted the neurology department. The emergence of severe acute respiratory syndrome coronavirus 2 in late 2019 has generated new challenges in healthcare systems across the globe. Similar to the fields of pulmonology and cardiology that saw an increase in research, the neurology department was in search of possible relationships between COVID-19 and other medical conditions. Research on the possible common pathophysiological mechanism between COVID-19 and migraine is currently being studied. The most recent hypothesis suggests the following: migraine is caused by an increased release of calcitonin gene-related peptide from the trigeminal ganglion, which will cause an increase in nitric oxide and IL-1β, resulting in vasodilation and inducing hyperalgesia. COVID-19 causes an increase in nod-like receptor protein 3, which causes the production of IL-1β and again induces an inflammatory response. This review article looks at the mechanisms of migraine and COVID-19, and tries to link a common pathophysiological pathway between the two. This report also serves as a gateway for further research regarding possible management that could potentially target both of these mechanisms.

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CGRP Receptor Antagonism in COVID-19: Potential Cardiopulmonary Adverse Effects

Cited by 16 publications

References 16 publications

Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients

Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients

A Pharmacological Review of Calcitonin Gene-Related Peptide Biologics and Future Use for Chronic Pain

The Pathophysiological Relationship Between Migraine and SARS-CoV-2 Infection: A Comprehensive Literature Review

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