Indomethacin for refractory COVID or post-COVID headache: a retrospective study

DOI: https://doi.org/10.1007/s13760- 021- 01790- 3

Abstract-Summary COVID-19, a disease caused by SARS-CoV-2, manifests with headache, both in the acute phase and as a post-infection symptom, which may be refractory to usual analgesics.

Investigate the therapeutic response of refractory COVID or post-COVID head-

ache to indomethacin.

A sample of 37 patients diagnosed with COVID-19 presenting headache during the acute phase or after the resolution of the disease, with refractoriness to the usual symptomatic medication was treated with indomethacin.

After treatment with indomethacin, 36 patients reported greater than 50% head-

ache relief from the third day and 5 became asymptomatic on the fifth day.

In patients with migraine or no prior history of headache who present with refrac- tory COVID or post-COVID headache to common analgesics, anti-inflammatory drugs, and/or triptans, indomethacin should be considered a therapeutic option.

Introduction Indomethacin was among the first NSAID used to treat headache in clinical practice including migraine and headache syndromes eventually known as “indomethacin- responsive” headaches [317].

5.2

COVID-19 and SARS-COV2 Vaccines

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Nitric oxide is known to induce headache and delayed migraine in patients

[318, 319].

COVID patients may have or not migraine as a comorbidity [320]. Headache may occur during or after COVID with no clear relationship with

migraine mechanisms [320–322].

Some patients with migraine and COVID may seek help in general practitioners or emergency departments and receive unspecific prescriptions for the head- ache itself.

Others will try using their usual acute migraine medications seeking to alleviate the head pain [218, 219, 321, 322]. This retrospective study aimed at describing the outcomes of indomethacin use in patients, with or without migraine, who presented headache not responding to their acute medication during COVID acute phase or after >10 days of confirmed infection by SARS-CoV-2.

Methods The study population comprised a non-random and convenience sampling, consist- ing of consecutive patients with and without migraine seeking help at a tertiary headache center, to whom indomethacin was prescribed.

Patients over 18 years of age diagnosed with COVID-19, through the RT-PCR positivity for SARS-CoV-2 and presenting headache during the acute phase or after the resolution of the disease, with refractoriness to the usual symptomatic medica- tion or to a symptomatic medication recently prescribed, for at least three days, were included in this study.

The study excluded patients with acute headaches from secondary causes, such as acute glaucoma or acute sinusitis, and over the age of 60 years and preg- nant women.

Patients were divided into two groups: in group 1, those diagnosed with migraine without aura, according to ICHD-3 criteria [323], presenting less than 15 days of headache per month and in group 2, patients with no previous history of headache.

Results Eight patients did not have a previous history of headache and were not patients of our center.

The remaining 29 were migraineurs and had a severe headache for at least three followed days during COVID-19 acute phase (n = 21) or started a daily headache for at least three followed days after a minimum of 10 days having tested positive for Sars-Cov-2 (n = 8).

The other 13 migraine patients reported a headache that started after 10–16 days of testing positive for Coronavirus and they had, during the acute phase, mild or moderate respiratory symptoms.

Four patients seek help at local hospitals during the acute phase. Among the 8 patients without migraine, 5 (62.5%) had a severe headache during

the acute phase and 3 after 10–13 days thereafter.

Thirty-six patients reported greater than 50% headache relief from the third day

and five became asymptomatic on the fifth day.

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5 Future Directions

Discussion The true prevalence of headache in COVID patients is uncertain.

In a review of 78 studies consisting of 104,751 COVID-19 patients, headache

was reported in 26,464 patients with a cumulative prevalence of 25.26% [324].

No clear mechanisms have been reported on how these headaches emerge in

COVID-19 patients [246, 312].

The treatment of headache in COVID-19 patients may be difficult [325]. In a case report, a chronic migraine patient already in use of fremanezumab with

comorbidities COVID-19, had a refractory headache.

Indomethacin was already suggested as a useful treatment not only for COVID-19

headache, but, in addition, for COVID-19 induced dry cough [326].

The main reason why we chose indomethacin to these patients was the lack of efficacy referred by all when treating their headache with metamizole (usually pre- scribed in Brazil for COVID-19 patient with headache), paracetamol, other NSAID and triptans, which were used by the patients with comorbid migraine.

Acknowledgement A machine generated summary based on the work of Krymchantowski, Abouch V.; Silva-Néto, Raimundo Pereira; Jevoux, Carla; Krymchantowski, Ana Gabriela 2021 in Acta Neurologica Belgica.

Headache Attributed to Vaccination Against COVID-19 (Coronavirus SARS- CoV- 2) with the ChAdOx1 nCoV-19 (AZD1222) Vaccine: A Multicenter Observational Cohort Study