Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution
Edoardo Caronna, Alejandro Ballvé, Arnau Llauradó, Victor J Gallardo, Diana Maria Ariton Smera, Sofía Lallana, Samuel López‐Maza, Marta Olivé‐Gadea, Laura Quibus, Juan Luis Restrepo‐Vera, Marc Rodrigo‐Gisbert, Andreu Vilaseca, M. Hernández, Mónica Martínez‐Gallo, Alicia Alpuente, Marta Torres‐Ferrús, Ricardo Pujol‐Borrell, José Álvarez‐Sabín, Patricia Pozo‐Rosich
Abstract
Objective To define headache characteristics and evolution in relation to COVID-19 and its inflammatory response. Methods This is a prospective study, comparing clinical data and inflammatory biomarkers of COVID-19 patients with and without headache, recruited at the Emergency Room. We compared baseline with 6-week follow-up to evaluate disease evolution. Results Of 130 patients, 74.6% (97/130) had headache. In all, 24.7% (24/97) of patients had severe pain with migraine-like features. Patients with headache had more anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Clinical duration of COVID-19 was shorter in the headache group (23.9 ± 11.6 vs. 31.2 ± 12.0 days; p = 0.028). In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. After 6 weeks, of 74 followed-up patients with headache, 37.8% (28/74) had ongoing headache. Of these, 50% (14/28) had no previous headache history. Headache was the prodromal symptom of COVID-19 in 21.4% (6/28) of patients with persistent headache ( p = 0.010). Conclusions Headache associated with COVID-19 is a frequent symptom, predictive of a shorter COVID-19 clinical course. Disabling headache can persist after COVID-19 resolution. Pathophysiologically, its migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia.