Blocking CGRP with the migraine drug olcegepant reduced permanent weight loss and IL-6 inflammation in older mice infected with SARS-CoV-2.
CGRP-null mice: no IL-6Mice genetically lacking CGRP showed virtually no IL-6 inflammatory response to COVID infection
What the researchers found
Older mice (over 18 months, roughly equivalent to elderly humans) infected with mouse-adapted SARS-CoV-2 showed neurological symptoms including fever, dizziness, and nausea in two wild-type strains (C57BL/6J and 129/SvEv).
Olcegepant treatment protected against the permanent weight loss seen after infection. It also dramatically reduced IL-6 levels in both mouse strains. The most striking finding: CGRP-knockout mice (lacking the alpha-CGRP gene entirely) showed virtually no IL-6 release after infection.
The fever, dizziness, and nausea occurred in all older mice regardless of treatment, suggesting CGRP blockade acts on the inflammatory cascade rather than preventing initial neurological symptoms.
Why it matters
COVID-19 neurological symptoms (headache, dizziness, brain fog) have been a persistent challenge. CGRP is a known neuroinflammatory mediator. This study shows that blocking CGRP can reduce the inflammatory cytokine response to SARS-CoV-2, particularly IL-6 (which was associated with severe COVID-19 outcomes). If confirmed, migraine drugs could be repurposed for COVID-19 neurological complications.
The numbers in context
- Mice over 18 months old (equivalent to elderly humans)
- Two wild-type strains tested: C57BL/6J and 129/SvEv
- CGRP-null mice: virtually no IL-6 release
- Olcegepant: reduced permanent weight loss and IL-6 in both strains
- All older mice developed fever, dizziness, and nausea regardless of treatment
How the study worked
Researchers infected C57BL/6J mice, 129/SvEv mice, and 129S αCGRP-null mice with mouse-adapted SARS-CoV-2. Older mice (over 18 months) were used because age is a major COVID-19 risk factor. They tested olcegepant (CGRP receptor antagonist) for protection against weight loss and measured IL-6 levels and neurological symptoms (fever using thermoregulation, dizziness using postural sway, nausea using behavioral surrogates).
Who was studied
Older mice (>18 months) of three strains infected with mouse-adapted SARS-CoV-2
What this study cannot tell us
This was tested in mice with mouse-adapted SARS-CoV-2, not human COVID-19. The mouse strains and viral adaptation may not replicate human disease. Olcegepant is an intravenous CGRP blocker not approved for clinical use (gepant pills like rimegepant are available). The study measured acute IL-6 and weight loss but not long-term neurological outcomes. The behavioral surrogates for human neurological symptoms are approximations.
How to read the evidence
Rated preliminary: animal study with mouse-adapted SARS-CoV-2, not human COVID-19. The model and drug may not directly translate.
When this study was published
Published in 2024. Relevant to ongoing research into neurological effects of COVID-19 and long COVID.
The bigger picture
COVID neurological symptoms like headache, dizziness, and brain fog are persistent challenges. CGRP is a known neuroinflammatory mediator, and blocking it could address the inflammatory component of COVID neurological disease.
Questions still open
- Could gepant drugs help with long COVID neurological symptoms?
- Does this CGRP-inflammation link apply to other viral infections?
Common questions
Could migraine drugs help COVID symptoms?
What is CGRP's role in COVID inflammation?
Read the original research
Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.
Journal of virology, 98(7), e0006624
Citation
Rahman, Shafaqat M; Buchholz, David W; Imbiakha, Brian; Jager, Mason C; Leach, Justin; Osborn, Raven M; Birmingham, Ann O; Dewhurst, Stephen; Aguilar, Hector C; Luebke, Anne E. (2024). Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2-infected older mice with neurological signs.. Journal of virology, 98(7), e0006624. https://doi.org/10.1128/jvi.00066-24