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

DOI: https://doi.org/10.1007/s40122- 021- 00296- 3

Abstract-Summary The most frequently reported neurological adverse event of ChAdOx1 nCoV-19 (AZD1222) vaccine is headache in 57.5%.

For the differential diagnosis of headaches attributed to this vaccine and head- aches attributed to CVT, it is of central clinical importance whether and, if so, how the phenotypes and course of these headaches can be differentiated.

The study aims to examine in detail the phenotype of headache attributed to this

vaccine.

The primary outcomes of this study are the clinical features of headaches after

vaccination.

A total of 2464 participants reported headaches after vaccination with the

ChAdOx1 nCoV-19 (AZD1222) vaccine.

Headaches attributed to COVID-19 vaccination with the ChAdOx1 nCoV-19 (AZD1222) vaccine demonstrate an extensive and characteristic complex of symptoms.

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The findings have several important clinical implications for the differentiation

of post-vaccinal headache and other primary as well as secondary headaches.

Extended: The primary outcomes of this study are the clinical features of head- ache after vaccination against COVID-19 with the ChAdOx1 nCoV-19 (AZD1222) vaccine.

Headaches attributed to COVID-19 vaccination with the ChAdOx1 nCoV-19 (AZD1222) vaccine show an extensive complex of symptoms with concise clinical characteristics.

Headaches attributed to systemic viral infection are also described. Headaches attributed to a systemic viral infection require, according to ICHD-3 [28], diagnostic evidence of a systemic viral infection without evidence of meningi- tis or encephalitis.

On the basis of the findings, new diagnostic criteria for this form of headache can

be developed.

Introduction This study is part of a series of analyses of headache as a side effect following vac- cination against COVID-19 with various vaccinees.

We report on the phenotype of headache attributed to vaccination against COVID-19 (coronavirus SARS-CoV-2) with the ChAdOx1 nCoV-19 (AZD1222) vaccine.

According to the data available, the most frequently reported neurological adverse event attributed to vaccination against COVID-19 (coronavirus SARS- CoV- 2) with the ChAdOx1 nCoV-19 (AZD1222) vaccine is headache in 57.5% of those vaccinated [327–330].

Several cases of cerebral venous thrombosis and other unusual thrombotic events with thrombocytopenia have developed after vaccination with ChAdOx1 nCoV-19 (AZD1222) vaccine [331].

The aim of this study is thus to delineate the detailed clinical characteristics of headaches occurring after vaccination against COVID-19 with the ChAdOx1 nCoV-19 (AZD1222) vaccine.

Methods This continuous multicenter observational cohort study accompanying the COVID-19 vaccination campaign aims to analyze the headache phenotype after vaccination with the ChAdOx1 nCoV-19 (AZD1222) vaccine.

Since direct contact with the vaccines is not possible because of data protection regulations, the management of the residential care homes was contacted by email and asked to pass on the information about the study to the residents and staff.

Subjects were informed at the beginning of the questionnaire that data were col- lected anonymously, meaning that as a result of this anonymization it would not be possible to revoke participation in the study after any answers have been sent.

Medical staff in tertiary university hospitals and people being cared for in resi- dential care homes for the elderly are overrepresented in this study compared to the general population, as both belonged to the groups with the highest vaccination priority in Germany.

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Results In participants with a history of migraine, there was no effect on the time between the vaccination and the onset of the headache compared to participants who had no primary headache.

Headache duration after COVID-19 vaccination was significantly longer in patients with a history of migraine than in participants without primary headache (20.9 ± 32.6 vs. 13.0 ± 18.5 h; p = 0.002).

Patients with migraine (3.7 ± 0.8 vs. 3.2 ± 0.9; p < 0.001) and tension-type head- ache (3.5 ± 0.8 vs. 3.2 ± 0.9; p < 0.010) reported a significantly higher headache pain intensity on the verbal rating scale (VRS 0–5) after COVID-19 vaccination compared to participants who had no history of migraine.

Discussion The specific set of accompanying symptoms along with the temporal and spatial headache characteristics characterize a unique headache phenotype for headaches attributed to COVID-19 vaccination.

It may be possible that clinical symptoms of these two primary headaches are included in the questionnaire reports and overlap with the headache phenotype attributed to COVID-19 vaccination.

The described symptom complex of headache attributed to COVID-19 vaccina- tion with the ChAdOx1 nCoV-19 (AZD1222) differs markedly from the aforemen- tioned primary headaches.

The findings described in this report provide an overview of the phenotype of this headache, which can occur in more than 57% of the participants after vaccina- tion as the most frequent neurological symptom [327, 328].

Whether the headache phenotype described here occurs in the same way or in a different form with other vaccines against COVID-19 remains still open and is sub- ject to further subgroup analyses in this study series [332].

Conclusions Headaches attributed to COVID-19 vaccination with the ChAdOx1 nCoV-19 (AZD1222) vaccine demonstrate an extensive and characteristic complex of symptoms.

The set of accompanying symptoms, along with the temporal and spatial head- ache characteristics describe a unique headache phenotype for headaches attributed to COVID-19 vaccination.

The findings have several important clinical implications for the differentiation

of post-vaccinal headache and other primary as well as secondary headaches.

Acknowledgement A machine generated summary based on the work of Göbel, Carl H.; Heinze, Axel; Karstedt, Sarah; Morscheck, Mascha; Tashiro, Lilian; Cirkel, Anna; Hamid, Qutyaba; Halwani, Rabih; Temsah, Mohamad-Hani; Ziemann, Malte; Görg, Siegfried; Münte, Thomas; Göbel, Hartmut 2021 in Pain and Therapy.

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Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis