Frequency and phenotype of headache in covid-19: a study of 2194 patients

DOI: https://doi.org/10.1038/s41598- 021- 94220- 6

Abstract-Summary To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. Period, 2194 patients out of the population at risk were diagnosed with

COVID-19.

Headache was described by 514/2194 patients (23.4%, 95% CI 21.7–25.3%),

including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients.

The headache phenotype was studied in detail in 458 patients (mean age, 51

years; 72% female; prior history of headache, 49%).

Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and per-

sisted after 1 month in 13% of patients.

Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.

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Extended: Period, 2194 patients out of the at-risk population of 261,431 were diagnosed with COVID-19, leading to a COVID-19 incidence of 8.4 cases per 1000 people.

Headache was the most frequent first symptom of COVID-19, described by 128 (27.9%) of the patients who reported headache, followed by fever in 109 (23.1%), cough in 60 (13.1%), asthenia in 32 (7.0%).

Headache was the first COVID-19 symptom in at least 128/2194 (5.8%) patients

when COVID-19 patients without headache were included.

Future studies should employ headache-specific questionnaires to evaluate the

disability caused by headache in a more standardized way.

Introduction The true frequency and phenotype of headache with COVID-19 is still unclear, as most of the available studies are series of hospitalized patients [213, 252–256].

The first series in confirmed COVID-19 patients described headache presenta-

tion within the first 72 h of the disease in most cases [257–259].

It is unknown whether headache can be misdiagnosed as a primary headache

disorder in COVID-19 patients managed in an outpatient setting.

In hospitalized patients, the presence of headache independently predicted a lower risk of mortality [252], and lower risk of intensive care-unit admission [220, 260].

The aims of this study are to estimate the incidence of headache over the COVID-19 disease course in the general population and to characterize the clinical phenotype of headache in patients with confirmed COVID-19.

Methods The study population included patients with confirmed COVID-19 and presence of headache at any point over the COVID-19 disease course.

Patients who reported symptoms suggestive of COVID-19 were followed daily

or every other day by phone or in-person.

We identified patients from the database of primary care COVID-19 teams and

hospital registrations and admissions.

We systematically screened all patients that were evaluated between March 8,

2020 (first confirmed COVID-19 case in the healthcare area) and April 11, 2020.

In addition, all covid-19 patients were interviewed directly about the presence of headache by a member of the study team, which was composed of 2 neurologists and 16 primary care physicians with prior training in headache disorders.

The main objectives were: (1) to estimate the incidence of headache over the course of COVID-19 in the general population and (2) to characterize the clinical phenotype of the headache in patients with COVID-19.

Variables A physician also analyzed prior history of headache, including the specific diagno- sis, the source of the diagnosis, the frequency of headache (days per month in the preceding 3 months), and the degree of similarity between the headache

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COVID-19 and SARS-COV2 Vaccines

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experienced during the course of COVID-19 and their usual headache on a 0–100% rating scale (0: completely different, 100%: exactly the same).

A physician also asked all participants about the prior history of headache in temporal relation to prior infections and whether those were similar to the present one.

Data were analyzed both per intention to treat (ITT), dividing the number of COVID-19 cases presenting with headache by the total number of confirmed COVID-19 cases (i.e. entire population of the area, including those that were not able to be screened for the study); and per protocol (PP), dividing the number of COVID-19 cases presenting with headache by the population that we were able to screen.

Results The age of headache patients ranged between 18 and 97 years, with a median age of 51 (IQR: 42–61) years.

Patients judged the similarity between the present headache and the usual head-

ache as 0% (median; IQR 0–50%) similar.

Patients described prior episodes of headache in temporal relation to prior infec- tions in 159 (34.7%) cases and described the headache as similar to the present episode in 99 (62.2%) of those 159 cases.

Headache was the most frequent first symptom of COVID-19, described by 128 (27.9%) of the patients who reported headache, followed by fever in 109 (23.1%), cough in 60 (13.1%), asthenia in 32 (7.0%).

Headache was the first COVID-19 symptom in at least 128/2194 (5.8%) patients

when COVID-19 patients without headache were included.

Median intensity of the headache was 7 out of 10 (IQR 6–8), and patients judged

the degree of disability caused by the headache as 50% (IQR 20–80%).

Discussion In our sample, we estimated that headache was the first symptom of COVID-19 in 6% of patients, with an early onset in most of the cases.

The phenotype of headache attributed to acute SARS-CoV-2 infection shows a bilateral headache predominantly affecting the forehead, with pressing quality, with severe intensity, and frequently accompanied by typical migraine symptoms, in line with previously published studies [257, 258].

Some features of headache, such as worsening with head movement, ocular movement, photophobia or phonophobia could be caused by the above immune responses [261, 262]; however, these features were not described by all patients in this study.

Prior large studies described a higher frequency of headache in female

patients [252].

The study of patients with phenotypes similar to new daily persistent headache, and those factors associated with a longer headache duration, are still understudied.

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Conclusion Most patients describe a bilateral headache with frontal predominance, an oppres- sive quality, and severe intensity.

We did not observe overall phenotypic differences in headache between inpa- tients and outpatients or between sexes except for photophobia, which was more frequent in hospitalized patients and females.

Prior history of headache was most frequent in female patients, who had more

intense headaches during COVID-19.

Acknowledgement A machine generated summary based on the work of García-Azorín, David; Sierra, Álvaro; Trigo, Javier; Alberdi, Ana; Blanco, María; Calcerrada, Ismael; Cornejo, Ana; Cubero, Miguel; Gil, Ana; García-Iglesias, Cristina; Lozano, Ana Guiomar; Martínez Badillo, Cristina; Montilla, Carol; Mora, Marta; Núñez, Gabriela; Paniagua, Marina; Pérez, Carolina; Rojas, María; Ruiz, Marta; Sierra, Leticia; Hurtado, María Luisa; Guerrero Peral, Ángel Luis 2021 in Scientific Reports.

Headache characteristics in COVID-19 pandemic-a survey study