Objective To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S. Methods We used publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021 and June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post‐vaccination neurological event rates were compared between vaccine types and to age‐matched baseline incidence rates in the U.S. and rates of neurological events following COVID. Results Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0‐3) from inoculation. Guillain‐Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer‐BioNtech (BNT162b2) or Moderna (mRNA‐1,273; 0.15% vs 0.03% vs 0.03% of doses, respectively, p < 0.0001). The observed‐to‐expected ratios for GBS, CVT and seizure following Janssen vaccination were ≥1.5‐fold higher than background rates. However, the rate of neurological events after acute SARS‐CoV‐2 infection was up to 617‐fold higher than after COVID vaccination. Interpretation Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS‐CoV‐2 infection are up to 617‐fold higher than after COVID vaccination. ANN NEUROL 2022;91:756–771

Introduction Headache is a frequent adverse event after viral vaccines. We aimed to investigate the frequency and clinical associations of COVID-19 vaccine-related headache. Methods The characteristics, associations of this headache, main comorbidities, headache history following the influenza vaccine and during COVID-19 were investigated using a web-based questionnaire. Results A total of 1819 healthcare personnel (mean age: 44.4 ± 13.4 years, 1222 females), vaccinated with inactivated virus, contributed to the survey; 209 (11.4%) had been infected with COVID-19. A total of 556 participants (30.6%) reported headache with significant female dominance (36.1% vs. 19.3%), 1.8 ± 3.5 (median: 1; IQR: 0–2) days following vaccination. One hundred and forty-four participants (25.9%) experienced headache lasting ≥3 days. Headache was mostly bilateral without accompanying phenomena, less severe, and shorter than COVID-19-related headache. The presence of primary headaches and migraine were significantly associated with COVID-19 vaccine-related headache (ORs = 2.16 [95% CI 1.74–2.68] and 1.65 [1.24–2.19], respectively). Headache during COVID-19 or following influenza vaccine also showed significant association with headache following COVID-19 vaccine (OR = 4.3 [95% CI 1.82–10.2] and OR = 4.84 [95% CI 2.84–8.23], respectively). Only thyroid diseases showed a significant association (OR = 1.54 [95% CI 1.15–2.08]) with vaccine-related headache among the common comorbidities. Conclusion Headache is observed in 30.6% of the healthcare workers following COVID-19 vaccine and mostly experienced by females with pre-existing primary headaches, thyroid disorders, headache during COVID-19, or headache related to the influenza vaccine.

Background Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines. Methods All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated. Results There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75–0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63–76) for ischemic stroke and 0.76 (95% CI: 0.67–84) for intracranial hemorrhage, and >99% negative predictive value. Conclusion Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events.

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