Letter to the Editor From Abobaker and Darrat: “Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients”

Abobaker, Anis; Darrat, Milad

doi:10.1210/jendso/bvab052

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Consistently, the adoption of CGRP antagonists, which are new pharmacologic agents useful in hemicrania prophylaxis, in COVID-19 treatment has not been fully evaluated yet [ 17 ].…”

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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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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“…Consistently, the adoption of CGRP antagonists, which are new pharmacologic agents useful in hemicrania prophylaxis, in COVID-19 treatment has not been fully evaluated yet [ 17 ].…”

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

View full text Add to dashboard Cite

show abstract

“…These results are consistent with associated fever and vestibular symptoms observed in COVID patients (30, 31). Early in the pandemic, there was a controversy as to whether CGRP plasma levels were increased or decreased in COVID-19 disease (32, 33). However, a recent study with a relatively greater number of patients showed that elevated CGRP plasma levels are correlated with increased disease severity in hospitalized COVID-19 patients (34).…”

Section: Discussionmentioning

confidence: 99%

Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs

Rahman,

Buchholz,

Imbiakha

et al. 2023

Preprint

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COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.

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Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs

Rahman,

Buchholz,

Imbiakha

et al. 2024

J Virol

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COVID-19 can cause neurological symptoms such as fever, dizziness, and nausea. However, such neurological symptoms of SARS-CoV-2 infection have been hardly assessed in mouse models. In this study, we infected two commonly used wild-type mouse lines (C57BL/6J and 129/SvEv) and a 129S calcitonin gene-related peptide (αCGRP) null-line with mouse-adapted SARS-CoV-2 and demonstrated neurological signs including fever, dizziness, and nausea. We then evaluated whether a CGRP receptor antagonist, olcegepant, a “gepant” antagonist used in migraine treatment, could mitigate acute neuroinflammatory and neurological signs of SARS-COV-2 infection. First, we determined whether CGRP receptor antagonism provided protection from permanent weight loss in older (>18 m) C57BL/6J and 129/SvEv mice. We also observed acute fever, dizziness, and nausea in all older mice, regardless of treatment. In both wild-type mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that migraine inhibitors such as those blocking CGRP receptor signaling protect against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection, which may have repercussions for related pandemic or endemic coronavirus outbreaks. IMPORTANCE Coronavirus disease (COVID-19) can cause neurological symptoms such as fever, headache, dizziness, and nausea. However, such neurological symptoms of severe acute respiratory syndrome CoV-2 (SARS-CoV-2) infection have been hardly assessed in mouse models. In this study, we first infected two commonly used wild-type mouse lines (C57BL/6J and 129S) with mouse-adapted SARS-CoV-2 and demonstrated neurological symptoms including fever and nausea. Furthermore, we showed that the migraine treatment drug olcegepant could reduce long-term weight loss and IL-6 release associated with SARS-CoV-2 infection. These findings suggest that a migraine blocker can be protective for at least some acute SARS-CoV-2 infection signs and raise the possibility that it may also impact long-term outcomes.

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Letter to the Editor From Abobaker and Darrat: “Circulating Levels of Calcitonin Gene-Related Peptide Are Lower in COVID-19 Patients”

Cited by 3 publications

References 6 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

Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs

Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs

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