Headache as a feature of Covid-19
Headache is common in patients with Covid-19. In the first review of the neurological aspects of Covid-19, a study of 214 patients in Wuhan with confirmed SARS-Cov-2 infection, Mao et al noted headache in 28 (13.1%) patients.(1) This figure has subsequently been replicated in a metanalysis of over 3000 cases of Covid-19 in patients from Wuhan, of whom 15.4% patients experienced headache,(2) and a scoping review, including almost 60 000 patients from around the world, in it was found that 12% had headache.(3) Headache is of course a common feature of most viral infections, though the pathophysiology of this remains obscure. In some cases headache can be the presenting, or even the sole symptom. In other cases, it can come on after some of the other cardinal features (such as cough or fever), but then persist beyond the resolution of other symptoms. In some of these cases, it is likely that the effect of the cytokine response to SARS-Cov-2 infection triggers a tendency to primary headaches (most usually migraine), in much the same way that other, sometimes innocuous, events can trigger persistent daily headaches. Further phenotyping of headaches associated with SARS-Cov-2 infection, as well as fuller headache histories in these patients, would go a long way to improving our understanding of the reason behind the high prevalence of headache in Covid-19.
Concerns about headache medication and Covid-19
In the early stages of the pandemic in Europe, there was speculation that certain drugs that are commonly taken by patients with headache, notably ibuprofen and candesartan, could worsen symptoms in COVID-19. SARS-CoV2 host cell infection is mediated by the binding to angiotensin-converting enzyme 2 (ACE2). In a letter to the journal Lancet Respiratory Medicine, researchers hypothesised that diabetes and hypertension treatment with drugs that increase the expression of ACE2 (such as lisinopril or candesartan) might increase the risk of developing severe COVID-19, and that other drugs, including ibuprofen might exacerbate this.(4) Against this, however, are the potential positive effects of blocking ACE2 receptors in disabling viral entry into the heart and lungs, and decreasing inflammation. At present there is no convincing evidence that these drugs are deleterious in Covid-19, and pretty much all the major national and international cardiology societies continue to recommend their use. (5) Reassurance on the safety of continuing to taking non-steroidal anti-inflammatories has been published by the European Medicines Agency (https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19) and United States Food and Drug Administration (https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19).(6)
Patients with certain headache disorders (most usually episodic cluster headache) may occasionally take short course of steroids to abort or ameliorate their headaches. The use of steroids has in the past been associated with increased mortality in influenza infections,(7) and decreased viral clearance in Middle Eastern Respiratory Syndrome (MERS). Reports from China suggest that the latter may be the case in patients with Covid-19, but not the former.(8) The use of steroids should therefore be minimised, but not avoided altogether. Doses and treatment duration may need to be reduced to minimize the potential risk of exacerbating underlying SARS-Cov-2 infection.
Whilst CGRP is widely distributed in body tissues, and may play as yet incompletely understood roles in the immune modulation (particularly in mucosal defences, such as in the lungs), the use of treatments (including triptans, CGRP monoclonal antibodies and (where available) gepants) that impact CGRP mechanisms in the body do not cause immune suppression, and are not linked to increased severity of infection. Indeed, as I reported in a previous blog, vazegepant, an intranasal CGRP antagonist in development, is being used in clinical trials in the United States to ascertain whether it will reduce lung injury in Covid-19.
Challenging times in the clinic
The advent of a global pandemic has had a predictably seismic impact on normal business in headache management. Many consultants, GPs with specialist interest, and specialist nurses have been redeployed to frontline services, or to alternative supporting roles within their organisations. In the UK some headache consultants have been working in ITU or other general medical wards, while others have been dusting off their skills as stroke physicians. Even where deployment has not taken place, the ubiquitous takedown of routine outpatient appointments, and the suspension of face-to-face interventions such as Botox or greater occipital nerve (GON) blocks has caused major logistical and clinical difficulties, exacerbated by the uncertainly of when these services might be able to start again, and under what restrictions.
In the UK, the suspension of all regulatory activity by the National Institute for Heath and Care Excellence (NICE), has delayed the introduction of new treatments into the NHS in England and Wales. Fremanezumab (Ajovy) should have become available from 15th April 2020, but it is not (at the time of writing) clear when this approval will now be granted. There is also no clarity on when work will resume on the appeal for the use of erenumab (Aimovig) for patients who have tried and failed Botox as well as the standard three oral preventives, or commence on the application for galcanezumab (Emgality) for chronic migraine. Whilst entirely understandable in the circumstances, it is nonetheless frustrating that the process for fremanezumab in particular was curtailed less than two weeks from approval, as the availability of a drug of this type which can be delivered directly to patients at home would have been incredibly useful given the current restrictions.
There are also concerns about the long term effect of the pandemic on headache research. It seems likely that, over the next couple of years, funding for basic, clinical and epidemiological research will prioritise studies of the pandemic. Travelling to national and international congresses and meetings may come to be regarded as bringing unnecessary and unacceptable risks. Scientific debate will gravitate towards videoconferences, blogs, and society forums. As one European headache specialist puts it, “We will see a post-crisis Marshall Plan, and it will be up to us to be part of it.”(9)
Challenging times at home
Migraine likes people to be a bit boring. Many patients with migraine find that disruptions to their normal routine will trigger attacks. Lockdown brings new schedules, pressures and challenges when it comes to maintain physical and psychological well being. The approach to managing these challenges is no different now from before: getting up at the same time every day, structuring the day with regular breaks, minimizing distractions, stopping for lunch, getting fresh air and exercise, avoiding prolonged periods of immobility (especially if it involves a phone, tablet, or laptop), keeping well-hydrated, and practising good sleep hygiene. It’s important to avoid the temptation to increase alcohol consumption, and to rely on ready-made meals that contain additives such as MSG. Relaxation techniques, such as breathing exercises, meditation, mindfulness, and so on, may be helpful for some people.
In conditions of social isolation, depression and anxiety may worsen. This can adversely affect headache disorders, and lead to medication overuse. Stress and anxiety can often be managed by focussing on those things that are within one’s control (such as hand washing, staying at home, and ensuring a sufficient supply of acute and preventive medications), and avoiding the barrage of social media updates and news reports about the pandemic. If this is not enough, it’s important to have a low threshold for reaching out for support, picking up the phone, staying in touch with friends and family, or actively seeking professional support.
Solutions and opportunities
It seems clear that there will be an exponential increase in the use of telemedicine for headache management. If our experiences in lockdown have taught us anything, it is how to use Zoom, or Teams, or Skype, or any of the other widely available videoconferencing platforms. Previous research on telemedicine for headache care has shown that patients find it convenient,(10) with similar satisfaction rates and outcomes to traditional face-to-face consultations.(11,12) Factors that have until now prevented more widespread use – including technological limitations, concerns about privacy and confidentiality, and inertia – have been rapidly swept aside in the era of COVID‐19, given the need for significant social distancing precautions.
As mentioned above, one of the most frustrating effects of the pandemic on headache management, particularly in England Wales, is the delay in the final approval of the first of the new CGRP antibodies to receive a positive opinion from NICE. Where these drugs are already available, they have played an extraordinarily important part in keeping people with chronic migraine well. In Italy, for example, where government restrictions made it difficult for patients to pick up their drugs, virtually all of them made the effort to do, some travelling two hours by car to avoid “falling back into the abyss of their migraine attacks”.(13) In the UK we have been actively exploring ways in which we might be able to move this process forward, and we hope to be able to announce progress in this area soon.
Many media commentators and life coaches are encouraging us to take the opportunity of lockdown to learn new skills, or to get involved in new activities. People with migraine in the UK could consider joining the Migraine Trust’s Volunteer Forum, sharing their migraine stories with the Trust and the wider community, or by signing up for the Trust’s ebulletin or following them on social media. You can find out more about the work of the Trust, including the Volunteer Forum, on the Trust’s website (www.migrainetrust.org). The National Migraine Centre, a charity that runs a clinic in London and, amongst other things, publishes the entertaining and informative Heads Up podcast, also needs increased support (like all charities) in these difficult times (www.nationalmigrainecentre.org.uk).
- Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020. Published online April 10, 2020. doi:10.1001/jamaneurol.2020.1127
- Zhu J, Ji P, Pang J, et al. Clinical characteristics of 3,062 COVID-19 patients: a meta-analysis. J Med Virol2020. Published online April 15, 2020. doi: 10.1002/jmv.25884
- Borges do Nascimento I, Cacic N, Abdulazeem H, et al. Novel Coronavirus Infection (COVID-19) in Humans: A Scoping Review and Meta-Analysis. J Clin Med 2020 Mar 30;9(4). pii: E941. doi: 10.3390/jcm9040941
- Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020. Published online, 11 Marc, 2020. doi.org/10.1016/PII
- Rico-Mesa J, White A, Anderson A. Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB. Curr Cardiol Rep 2020. 22(5):31. doi: 10.1007/s11886-020-01291-4
- Maassen Van Den Brink A, de Vries T, Danser A. Headache medication and the COVID-19 pandemic. J Headache Pain 2020. https://doi.org/10.1186/s10194-020-01106-5
- Sytsma T, Greenlund L, Greenlund L. Joint corticosteroid injection associated with increased influenza risk. Mayo Clinic Proceedings Innovations, Quality And Outcomes 2018; 2: 194–8
- Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020. 395: 497-506
- Martelletti, P. An unexpected and suspended time. J Headache Pain 212020. https://doi.org/10.1186/s10194-020-01112-7
- Qubty W, Patniyot I, Gelfand A. Telemedicine in a pediatric headache clinic: A prospective survey. Neurology 2018; 90: e1702‐ e1705
- Muller KI, Alstadhaug KB, Bekkelund SI. Telemedicine in the management of non‐acute headaches: A prospective, open‐labelled non‐inferiority, randomised clinical trial. Cephalalgia 2017; 37: 855‐ 863
- Muller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology 2017; 89: 153‐ 162
- Silvestro M,Tessitore A,Tedeschi G, Russo A. Migraine in the Time of COVID‐19. Headache 2020. Published online, 8th April, 2020. https://doi.org/10.1111/head.13803