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

César Fernández-de-las-Peñas Dr. Med, PhD; Maria L. Cuadrado MD, PhD; Victor Gómez-Mayordomo MD; Juan Torres-Macho MD; Oscar J. Pellicer-Valero PhD; José D. Martín-Guerrero PhD; Lars Arendt-Nielsen Dr. Med, PhD

Disclosures

Headache. 2022;62(9):1148-1152. 

In This Article

Abstract and Introduction

Abstract

Objective: This study looked at differences in the presence of headache as an onset symptom of coronavirus disease 2019 (COVID-19) and as a post-COVID-19 symptom in individuals previously hospitalized owing to infection with the Wuhan, Alpha, or Delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background: Headache can be present in up to 50% of individuals during the acute phase of SARS-CoV-2 infection and in 10% of subjects during the post-COVID-19 phase. There are no data on differences in the occurrence of headache in the acute- and post-COVID-19 phase according to the SARS-CoV-2 variants.

Methods: A cross-sectional cohort study was conducted. Unvaccinated subjects previously hospitalized for COVID-19 caused by the Wuhan (n = 201), Alpha (n = 211), or Delta (n = 202) SARS-CoV-2 variants were scheduled for a telephone interview 6 months after hospital discharge. Hospitalization data were collected from hospital medical records.

Results: The presence of headache as a COVID-19 onset symptom at hospitalization was higher in subjects with the Delta variant (66/202, 32.7%) than in those infected with the Wuhan (42/201, 20.9%; odds ratio [OR] 1.83, 95% confidence interval [CI] 1.17–2.88) or Alpha (25/211, 11.8%; OR 3.61, 95% CI, 2.16–6.01) variants. The prevalence of post-COVID-19 headache 6 months after hospital discharge was higher in individuals infected with the Delta variant (26/202, 12.9%) than in those infected with the Wuhan (11/201, 5.5%; OR 2.52, 95% CI 1.22–5.31) or Alpha (eight of 211, 3.8%; OR 3.74, 95% CI 1.65–8.49) variants. The presence of headache as a COVID-19 onset symptom was associated with post-COVID-19 headache in subjects infected with the Wuhan (OR 7.75, 95% CI 2.15–27.93) and Delta variants (OR 2.78, 95% CI 1.20–6.42) but not with the Alpha variant (OR 2.60, 95% CI 0.49–13.69).

Conclusion: Headache was a common symptom in both the acute- and post-COVID-19 phase in subjects infected with the Wuhan, Alpha, and Delta variants but mostly in those infected with the Delta variant.

Introduction

Headache is one of the symptoms that may be experienced at the acute phase of coronavirus disease 2019 (COVID-19),[1] and it may be also experienced as a post-COVID-19 symptom.[2] A meta-analysis investigating headache and COVID-19 reported a prevalence of 47.1% of headache as an onset symptom and 10% as a post-COVID-19 symptom during the first 6 months after the infection.[3] Interestingly, the presence of headache as an onset symptom is associated with a more benign course of the disease[4] but is also associated with a higher prevalence of post-COVID-19 headache.[5] Therefore, proper understanding of the association between headache and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection seems to be crucial.

After the historical SARS-CoV-2 variant discovered in Wuhan, several variants have been identified (i.e., Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Lota, Kappa, Lambda, and Omicron). Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and recently Omicron (B.1.1.529/BA.1) have been considered as variants of concern.[6] To date, all studies investigating the association of headache and COVID-19 have included individuals infected with the Wuhan variant.[3] Consequently, there are no data to our knowledge on the differences in the occurrence of headache in the acute- and post-COVID-19 phase according to the SARS-CoV-2 variants causing the disease. The aim of this study was to analyze headache as a COVID-19 onset symptom and as a post-COVID-19 symptom in patients hospitalized with three different variants of concern: Wuhan, Alpha, and Delta. We hypothesized that no differences in the presence of headache as a COVID-19 onset symptom or as a post-COVID-19 symptom would be observed between individuals infected with the Wuhan, Alpha, or Delta variants of SARS-CoV-2.

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