Headache Symptom Versus Headache Disorders: Impact on COVID-19 Survival

Abstract

Background: COVID-19 has not impacted people or countries uniformly. This disparity has prompted investigations to identify clinical and genetic predictors of COVID-19 mortality. Headache, a COVID-19 symptom, has been associated with positive disease prognosis in small cohorts, but larger confirmatory data-sets are lacking. Moreover, the global predisposition to experience primary headache disorders might be correlated with variances in COVID-19 mortality rates.\xa0 \n \nMethods: We conducted a meta-analysis of studies of COVID-19 inpatient survival that also reported headache as a COVID-19 symptom. Separately, using a generalized additive model regression (GAM), we analysed data across 171 nations to identify variables which impact COVID-19 mortality rates. We performed similar analyses of seasonal influenza mortality. Prevalence data were extracted from the Global Health Data Exchange.\xa0 \n \nFindings: We meta-analysed 48 studies and observed a significantly higher risk ratio of survival (RR:2·178 [1·882-2·520], p<0·0001) among COVID-19 inpatients with headache. In the global population-level analysis, we observed that a higher prevalence of headache disorders was associated with a higher COVID-19 mortality rate, and represented the main variable contributing to differences in COVID-19 mortality rates between countries (37·8%;\xa0F\xa0value=10·68). By contrast, we observed a negative trend between the prevalence of headache disorders and influenza death rates. \n \nInterpretation: Headache as a COVID-19 symptom enhances survival, whereas headache as a primary disorder is more prevalent in nations with higher COVID-19 mortality. Further studies should investigate (1) mechanisms whereby headache is associated with survival from certain viral infections and (2) whether selection pressures from viruses may have contributed to the evolution of primary headache disorders as adaptations. \n \nFunding: No funding was received \n \nDeclaration of Interests: Dr Shapiro has received in the past 12 months financial or editorial compensation as a research consultant for Eli Lilly and Lundbeck. Mr Gallardo reports no disclosures. Dr Caronna reports no disclosures. Dr Pozo-Rosich has received honoraria as a consultant and speaker for: Allergan-AbbVie, Almirall, Biohaven, Chiesi, Eli Lilly, Medscape, Neurodiem, Novartis and Teva. Her research group has received research grants from Novartis; has received funding for clinical trials from Alder, Amgen, Electrocore, Eli Lilly, Novartis, Teva. She is a trustee member of the board of the International Headache Society and the Council of the European Headache Federation. She is in the editorial board of Revista de Neurologia. She is an editor for Cephalalgia, Headache, Neurologia, Frontiers of Neurology and advisor for The Journal of Headache and Pain. She is a member of the Clinical Trials Guidelines Committee of the International Headache Society. She has edited the Guidelines for the Diagnosis and Treatment of Headache of the Spanish Neurological Society. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company. There are no conflicts of interest in regard to this manuscript.