What COVID-19 means for people with migraine: Infection, management, treatment, and medications

COVID-19 infection for people living with migraine

It is yet unclear if there are specific complications of COVID-19 for patients who experience migraine.³ However, a few reports have been published that may start to shed light on possible connections.^3,4 First, a group from Wuhan, China reported that neurological manifestations including headache are associated with COVID-19,⁴ albeit it was unclear if the patients in these case studies had underlying headache or migraine. 

In a separate migraine-specific case study from the US, one patient with episodic migraine (EM) and another patient with chronic migraine (CM) both developed severe headache associated with COVID-19.³ In the first case, a patient with EM experienced headache that felt different from their typical migraine attack daily for one week before the onset of other typical COVID-19 symptoms; the headache, along with other symptoms, resolved within days after diagnosis.³ In the second case, a patient with CM on prophylactic medication also developed severe intractable headache, different from their usually experienced migraine, one week prior to onset of other COVID-19 symptoms; in this case, their headache continued after other symptoms subsided and warranted increased migraine medication to resolve.³ Though it is still unclear whether this early headache is prevalent in patients infected with COVID-19, and additional larger studies are necessary, patients and HCPs could take additional precautions.³ 

Another potentially important aspect regarding COVID-19 infection for people living with migraine is related to vascular involvement in migraine pathophysiology, with a particular emphasis on the vascular endothelium.⁵ Endothelial cell involvement in COVID-19 infection has been reported, providing a possible link to explain the increased vulnerability of patients with pre-existing endothelial dysfunctions to adverse outcomes upon COVID-19 infection.⁶

Such risk factors include male sex, smoking, hypertension, diabetes, obesity, and cardiovascular disease.⁶ These findings are worth noting, perhaps especially for people living with migraine with aura, which has recently been contextualized among other prevalent cardiovascular risk factors.⁷ Since hypertension and other cardiovascular diseases are common comorbidities especially among people with CM,⁸ headache specialists may need to stay vigilant for signs of complications, pending further research.

Effect of the pandemic on migraine treatment with a focus on chronic migraine

Expert guidance on migraine treatment in the light of the COVID-19 pandemic has been published by a group of specialists in the US,² as well as an updated review on implications of COVID-19 for patients with headache and their medications.⁹ Importantly, the current pandemic has highlighted significant weaknesses in the US healthcare and insurance system; these weaknesses have posed obstacles for patients and HCPs in taking measures such as utilizing telemedicine, bypassing insurance hurdles, and providing or switching treatment while avoiding inpatient visits and emergencies.² Many HCPs are calling for policy changes to aid in successfully managing migraine while maintaining social distancing.^2,10

The gap in treatment for patients with chronic migraine who were receiving regular inpatient care is one major global concern for migraine specialists, since these patients represent a cohort that has been suffering from debilitating symptoms for years, and have failed numerous other treatments.¹¹ These patients are at high risk of losing significant progress that they have made with treatment.¹² Studies in Madrid, Spain showed that 15 out of 20 patients (75%) were dissatisfied with the halt in their treatment during the pandemic, and considered their symptoms to have worsened.¹² Several headache specialists have called for insurance policies to allow patients who were receiving inpatient treatment to be able to swiftly “bridge” their treatment with alternative medications while inpatient visits are postponed, which is currently a time-consuming or even impossible option to get approved in many global regions, including the US.² 

In terms of remote treatments, a tertiary headache center in Milan, Italy has implemented a remote program to ensure continued care for patients who had been in their chronic migraine medication overuse day hospital program,¹³ which provides one model for future outpatient interventions.

Importantly, how serious of a medical issue migraine is for patients and how important it is to continue treatment became apparent when an overwhelming number of patients traveled to pick up medication from the hospital even at the peak of the pandemic.¹⁴ This has motivated HCPs to strive for additional solutions in the “new normal” for people living with migraine.¹⁴

Update on migraine medications relevant to COVID-19

Possible interactions of CGRP-modulating treatments with COVID-19

Calcitonin gene-related peptide (CGRP) is a major pathophysiological modulator of migraine.¹⁵ Studies in animal models have suggested that excess CGRP could contribute to abnormal vascular reactivity.¹⁶ Theoretically, this could suggest that anti-CGRP monoclonal antibodies may be beneficial in preventing acute lung injury in humans, but there is no evidence to date that this can be related to COVID-19 or pneumonia that may arise as a complication.¹⁶ Nevertheless, a small molecule CGRP receptor antagonist is starting to be studied as a treatment for COVID-19 infection-associated pulmonary complications; this may pose further questions about the effect of other CGRP-inhibiting treatments that are approved for migraine in relation to COVID-19 infections going forward.¹⁶

Current evidence regarding RAS blockers and NSAIDs

Two medications widely used in migraine or headache treatment—renin-angiotensin system (RAS) blockers and non-steroid anti-inflammatory drugs (NSAIDs)—have been suggested to upregulate the expression of Angiotensin-Converting Enzyme 2 (ACE2), a protein which can facilitate COVID-19 entry into human cells.¹ 

The RAS regulates blood pressure,¹ and some RAS blockers have been classified as “possibly effective” for migraine prophylaxis in some regions.^17,18 Concerns have been raised in light of COVID-19 because RAS blockers have been found to upregulate ACE2 in animal studies; however, as high doses were required and effects were variable, additional studies are needed to reach any conclusions.¹ Furthermore, it is not clear whether or not RAS blockers increase ACE2 levels, and if so, whether this increase facilitates COVID-19 entry.¹ 

NSAIDs are also widely used by people living with migraine or headache, and has also been suggested to increase levels of ACE2 in animal studies;¹⁹ however, critical evidence to support strong conclusions is still missing.¹ While a literature search has reported that as of June 2020, there is no specific evidence against the use of NSAIDs in patients with or without COVID-19,²⁰ another publication has recommended using substitutes until there is enough evidence,²¹ illustrating the scarcity of data.

Stay vigilant for evolving recommendations

People living with migraine and their clinicians are, and will be, experiencing the impact of the COVID-19 pandemic both in terms of possible risks associated with infection as well as unexpected changes to their treatment plans.¹ It is important to stay calm and keep up with emerging information on how migraine and headache care may be affected moving forward, as the world and medicine continue to adapt in the coming months and years.²