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An illustration of silhouettes of three people with headache (depicted by red shading on various parts of their head), with facemasks on to depict the COVID-19 pandemic.

Migraine - Management

8 MIN

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

The coronavirus disease 2019 (COVID-19) global pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has not only directly affected many lives, but has also been posing serious concerns and risks for the treatment of other diseases, including headache and migraine.1 Maintaining patients’ health while keeping their families and healthcare providers (HCPs) safe has been a major driving force for medical teams all over the world.2

COVID-19 and patients 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 recent migraine-specific case study from the United States (US), one patient with episodic migraine (EM) and another patient with chronic migraine (CM) both developed severe headache whilst infected 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, and additional larger studies are necessary, patients and HCPs could take additional precautions.3

Another potentially important aspect regarding COVID-19 infection for patients 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 was recently reported, providing a possible link to explain the increased vulnerability of patients with pre-existing endothelial dysfunctions—which are associated with male sex, smoking, hypertension, diabetes, obesity, and cardiovascular disease—to adverse outcomes upon COVID-19 infection.6 These findings are worth noting, perhaps especially for patients with migraine with aura, which has recently been contextualised among other prevalent cardiovascular risk factors.7 Since hypertension and other cardiovascular diseases are common comorbidities especially among patients 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

In the United Kingdom and the Republic of Ireland, the COVID-19 pandemic has posed a significant challenge for both clinicians and patients.  As a result of the pandemic, many HCPs working in the migraine therapy area were reassigned to emergency care to help facilitate possible coronavirus outbreaks.9,10 Moreover, face to face consultations with patients were cancelled, and replaced with video consultations.9,10 Video consultations effectively managed pre-existing migraine patients safely by enabling maintenance of their care whilst keeping them away from hospitals and, thus, mitigating the risk of contracting COVID-19.9,10 However, challenges remained for those patients needing to receive treatments that are only administered in a clinical setting or for those new migraine patients; where an initial face-to-face consultation is imperative to establish a correct diagnosis.10 Expert guidance on migraine treatment from the US in the light of the COVID-19 pandemic was recently published,2 as well as an updated review about implications of COVID-19 on patients with headache and their medications.11

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 who have been suffering from debilitating symptoms for years, and have failed numerous other treatments.12 These patients are at high risk of losing significant progress that they have made with treatment.13 Studies in Madrid 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.13  Indeed, in a survey of over two thousand migraine patients in the UK, 58% patients reported that their migraines had gotten worse since March 2020 when the pandemic began.14 17% of those surveyed reported that their migraines had gotten worse because they were unable to access treatment or medication.14 Moreover, 17% of participants reported that appointments with specialists were either cancelled or postponed which could have facilitated the worsening of their migraine attacks.14 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,15 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 travelled to pick up medication from hospitals even at the peak of the pandemic.16 This has motivated HCPs to strive for additional solutions in the “new normal” for patients with migraine.16

Update on migraine medications relevant to COVID-19

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 (ACE) 2, 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 patients 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 In fact, a recent 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

Stay vigilant for evolving recommendations

Patients 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 evolve in the coming months and years.2

References
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  2. Szperka CL et al. Headache 2020; 60(5):833–42.

  3. Singh J, Ali A. Headache 2020; 60(8): 1773-76.

  4. Mao L et al. JAMA Neurol 2020; 77(6):683–90.

  5. Mason BN, Russo AF. Front Cell Neurosci 2018; 12.

  6. Varga Z et al. Lancet 2020; 395(10234):1417–8.

  7. Kurth T et al. JAMA 2020; 323(22):2281–9.

  8. Buse DC et al. J Neurol Neurosurg Psychiatry 2010; 81(4):428–32.

  9. Tomkins E et al. Headache 2020; ahead of print.

  10. The Migraine Trust. Where to get help during the pandemic- Assessing migraine healthcare during the covid-19 crisis. 2020. [Internet]; [cited November 2020]. Available from: https://www.migrainetrust.org/living-with-migraine/seeking-medical-advice/where-to-get-help-during-the-pandemic/.

  11. Bobker SM, Robbins MS. Headache 2020; 60(8): 1806-11.

  12. Ali A. Headache 2020; 60(6):1183–6.

  13. Porta-Etessam J et al. Headache 2020; 60(7): 1448-1449.

  14. The Migraine Trust. The impact of the crisis on migraine. A significant number of people's migraine has worsened. 2020. [Internet]; [Cited January 2021]. Available from: https://www.migrainetrust.org/the-impact-of-the-crisis-on-migraine/.

  15. Grazzi L, Rizzoli P. Headache 2020; 60(7): 1463-1464.

  16. Silvestro M et al. Headache 2020; 60(5):988–9.16.

  17. Parikh SK, Silberstein SD. Neurol Clin 2019; 37(4):753–70.

  18. Steiner TJ et al. J Headache Pain 2019; 20(1):57.

  19. Qiao W et al. Cardiology 2015; 131(2):97–106.

  20. Arca KN et al. Headache 2020; ahead of print.