Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution

• Published in: Cephalalgia Vol. 40; no. 13; pp. 1410 - 1421
• Main Authors: Caronna, Edoardo, Ballvé, Alejandro, Llauradó, Arnau, Gallardo, Victor José, Ariton, Diana María, Lallana, Sofia, López Maza, Samuel, Olivé Gadea, Marta, Quibus, Laura, Restrepo, Juan Luis, Rodrigo-Gisbert, Marc, Vilaseca, Andreu, Hernandez Gonzalez, Manuel, Martinez Gallo, Monica, Alpuente, Alicia, Torres-Ferrus, Marta, Pujol Borrell, Ricard, Alvarez-Sabin, José, Pozo-Rosich, Patricia
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.11.2020
• Subjects: Adult; Aged; Betacoronavirus; Biomarkers - blood; Coronavirus Infections - complications; Coronavirus Infections - immunology; COVID-19; Female; Headache - epidemiology; Headache - virology; Humans; Inflammation - blood; Inflammation - virology; Male; Middle Aged; Pandemics; Pneumonia, Viral - complications; Pneumonia, Viral - immunology; Prodromal Symptoms; Prospective Studies; SARS-CoV-2; Special Section; COVID-19; Headache; loss of smell; SARS-CoV-2; prognosis
• ISSN: 0333-1024; 1468-2982; 1468-2982
• DOI: 10.1177/0333102420965157

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.