Headache Identified as Common Symptom in COVID-19 Variants, Mainly Delta


Six months after hospital discharge, COVD-19 headache was more frequently observed in those infected with the Delta variant vs Wuhan or Alpha variants.

Lars Arendt-Nielsen, PhD, founder and director, Center for Sensory-Motor Interaction, Aalborg University

Lars Arendt-Nielsen, PhD

Findings from a cross-sectional cohort study of unvaccinated individuals hospitalized for COVID-19 caused by the Wuhan, Alpha, or Delta SARS-CoV-2 variants showed that headache is common in both the acute and post-COVID stages, with the prevalence of this symptom higher in those affected with the Delta variant. This was the first study observing acute- or post-COVID-19 phase headache based on SARS-CoV-2 variant.1

Although headache is present in up to 50% of those during the acute phase of SARS-CoV-2 and in 10% of those during the post-COVID-19 phase, little information had been gathered on the differences of this symptom based on the variant. In total, there were 201, 211, and 202 individuals hospitalized for the Wuhan, Alpha, and Delta SARS-CoV-2 variants, respectively, who were followed-up 6 months after discharge for a phone interview.

Senior investigator Lars Arendt-Nielsen, PhD, founder and director, Center for Sensory-Motor Interaction, Aalborg University, Denmark, and colleagues purposely did not include vaccinated individuals because of inconsistent evidence on the effects of vaccination on post-COVID-19 symptoms and the potential that vaccines may cause headache as a side effect. For those with referred headache, the structured phone interview included questions about its pain features, including location, quality, intensity, and possible accompanying symptoms.

Demographically, individuals with the Alpha variant were older than the other 2 (P <.001); however, there were no significant between-group differences in the presence of pre-existing history of migraine (P = .941). All told, the presence of headache as a COVID-19 onset symptom at hospital admission was higher in those infected with the Delta variant (32.7%) as compared with the Wuhan (20.9%; odds ratio [OR], 1.83; 95% CI, 1.17-2.88; P = .008) or Alpha (11.8%; OR, 3.61; 95% CI, 2.16-6.01; P <.001) variants. Arendt-Nielsen at el observed that headache as a COVID-19 onset symptom adopted features of tension-type-like headache.

Six months after discharge, the prevalence of post-COVID-19 headache was higher in those infected with the Delta variant (12.9%) than in those with the Wuhan (5.5%; OR, 2.52; 95% CI, 1.22-5.31; P = .012) or Alpha (3.8%; OR, 3.74; 95% CI, 1.65-8.49; P = .001) variants. As previously mentioned, post-COVID-19 adopted similar features to tension-type headache in 90% of the patients and to migraine in 10%, with no significant differences between the 3 observed groups.

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All told, findings from the study also showed that the presence of headache as a COVID-19 onset symptom was associated with the development of post-COVID-19 headache in those infected with Wuhan (OR, 7.75; 95% CI, 2.15-27.93; P = .002) or Delta (OR, 2.78; 95% CI, 1.20-6.42; P = .015) variants but not in those infected with the Alpha (OR, 2.60; 95% CI, 0.49-13.69; P = .257) variant. Of the 42 patients in the Wuhan cohort who had headache at onset, 8 (19%) persisted with post-COVID-19 headache.

The Delta cohort reported an even greater rate, as 16 of the 66 patients (24.2%) who had headache at onset had post-COVID-19 headache. Of the 25 patients in the Alpha cohort having headache at onset, 3 (12%) had post-COVID-19 headache. Notably, there were no other significant association between any hospital admission variable, incuding the presence of pre-existing migraine (Wuhan: OR, 1.80; 95% CI, 0.21-15.48; P = .592; Alpha: OR, not applicable; Delta: OR, 0.96; 95% CI, 0.11-8.18; P = .974) and the development of post-COVID-19 headache was observed.

"The development of headache in the acute- or post-COVID-19 phase could be related to a complex and multifactorial pathophysiology," the study investigators wrote. However, "we cannot determine the cause of differences found in the occurrence of headache with the three SARS-CoV-2 variants, but they are indicative of the clinical heterogeneity of COVID-19 across waves."

1. Fernandez-de-las-Penas C, Cuadrado ML, Gomez-Mayordomo V, et al. Headache as a COVID-19 onset symptom and post-COVID-19 symptom in hospitalized COVID-19 survivors infected with the Wuhan, Alpha, or Delta SARS-CoV-2 variants. Headache. Published online September 16, 2022. doi:10.1111/head.14398
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