Could CGRP Antagonists Be Helpful in the Fight Against COVID‐19?

Robertson, Carrie E.

doi:10.1111/head.13853

Cited by 24 publications

(19 citation statements)

References 13 publications

(17 reference statements)

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“…More relevant consideration will be systemic CGRP increase, possibly induced by both angiotensin II and IL-6 levels, as CGRP is clearly associated with trigemino vascular activation resulting in headache, increased gastrointestinal (GI) motility leading to diarrhea, further triggering in ammation and vascular edema. 7,25 Taken together with the unusually high rate of ageusia-anosmia (60.4%) this data may lead us to the footsteps of the viral pathway in the brain. Thus we may also suggest that neuronal invasion of this new coronavirus may cause the dysfunction of the network at brainstem sites, in addition to headache.…”

Section: Possible Mechanisms Underlying Covid-19 Related Headaches Inmentioning

confidence: 77%

The Emergence of a New Form of Headache in COVID-19 Pandemic Era

Uygun¹,

Ertaş²,

Eki̇zoğlu³

et al. 2020

Preprint

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BackgroundHeadache is the most common COVID-19-related neurological symptom. But, diagnostic clues of headache for COVID-19 infection are not well known. MethodsWe developed a detailed web-based questionnaire screening the characteristics and course of headaches besides clinical COVID-19 features. The participants were grouped according to being diagnosed with COVID-19 infection or not, and having previous or new-onset headaches. The COVID-19 related headache features and their associations with other clinical features were investigated. A binary logistic regression model was performed to differentiate the characteristics of headache related to COVID-19. Findings 3458 participants (2341 females;67.7%, 1495 healthcare workers;43.2%) with a mean age of 43.21±11.2 years experiencing headache during pandemic contributed to the survey. Among them, 262 participants had COVID-19 and 126(48.1%) were male. The rate of males in the group without COVID-19 was 31% (991 out of 3196 participants) showing significant gender difference between groups (p<0.000). COVID-19 related headaches were more closely associated with anosmia/ageusia and gastrointestinal complaints (RR=3.7 and RR=1.33, respectively), showed different characteristics like pulsating, pressing, and even stabbing quality. Logistic regression analyses showed that bilateral headache, duration over 72 hours, analgesic resistance and having male gender were significant variables to differentiate COVID-19 positive patients from those without COVID-19 (p<0.000 for all variables). A worsening of previous primary headaches due to the pandemic-related problems was not the rule in majority of patients.Interpretation Bilateral, long-lasting headaches, resistance to analgesics and having male gender were more frequent in people with COVID-19 in conjunction with the anosmia/ageusia and gastrointestinal complaints. These features may be helpful for COVID-19 diagnosis in the clinical evaluation of headache patients during the pandemic.Funding: This study was funded by Scientific Research Projects Coordination Unit of Istanbul University with a project number of GAP-36802.

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Section: Possible Mechanisms Underlying Covid-19 Related Headaches Inmentioning

confidence: 77%

The Emergence of a New Form of Headache in COVID-19 Pandemic Era

Uygun¹,

Ertaş²,

Eki̇zoğlu³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…A previous commentary suggested that CGRP antagonists may be helpful in the fight against COVID-19 [ 27 ] but, to the best of our knowledge, this is the first report on the reduced levels of the peptide in patients. CGRP belongs to a peptide family including also calcitonin, adrenomedullin, and amylin [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

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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“…Co‐existence of calcitonin gene‐related peptide (CGRP) with angiotensin system in small‐ and medium‐sized sensory neurons and trigeminal ganglia suggests that early activation of trigeminal nerve endings by the virus could initiate well‐known mechanisms that result in migraine‐like headache 3 . The correlation of circulating CGRP and pro‐inflammatory cytokine interleukin‐6 levels postulates a possible mechanism of headache in the later stage of the COVID‐19 illness 3,11 …”

Section: Discussionmentioning

confidence: 99%

Case Series of Headache Characteristics in COVID‐19: Headache Can Be an Isolated Symptom

et al. 2020

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Headache was reported in up to one‐third of the hospitalized patients; yet, the clinical characteristics of headache associated with coronavirus disease 2019 (COVID‐19) have not been defined. This observational case study included patients who were consulted to headache unit due to headache and had COVID‐19 illness. Headache features in 13 PCR‐confirmed COVID‐19 patients with mild symptoms were reported. Headache was the isolated symptom of the COVID‐19 in 3 patients and emerged as an early symptom during the disease course in all patients. Patients specified severe, rapid onset, unrelenting headache with migraine‐like features, as well as unusual sensory symptoms such as anosmia, and gastrointestinal symptoms such as diarrhea and loss of appetite and weight. Headache lasted up to 3 days in 70% of the patients and resolved in all patients within 2 weeks. Despite the fact that most of the patients were female and headache characteristics were suggestive of migraine, majority of patients were not suffering from primary headaches. It was concluded that headache could be an isolated symptom of COVID‐19, which might possibly be ignored in asymptomatic patients. Headaches associated with COVID‐19 included features resembling migraine and/or atypical symptoms including anosmia and diarrhea.

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Could CGRP Antagonists Be Helpful in the Fight Against COVID‐19?

Cited by 24 publications

References 13 publications

The Emergence of a New Form of Headache in COVID-19 Pandemic Era

The Emergence of a New Form of Headache in COVID-19 Pandemic Era

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

Case Series of Headache Characteristics in COVID‐19: Headache Can Be an Isolated Symptom

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