Headache is an important manifestation during SARS-CoV-2 infection. In this study, we aim to identify factors associated with headache in COVID-19 and headache characteristics.
This case-control study includes COVID-19 hospitalized patients with pneumonia during March 2020. Controls comprise COVID-19 patients without headache and cases, COVID-19 patients with headache. Demographic, clinical and laboratory data were obtained from the medical records. Headache characteristics were evaluated by semi-structured telephonic interview after discharge.
Of a total of 379 COVID-19 patients, 48 (13%) developed headache. Among these, 30 (62%) were men and the median age was 57.9 (47-73) years. Headache was associated with younger age, less comorbidities and reduced mortality, as well as with low levels of C-Reactive Protein, mild acute respiratory distress syndrome (ARDS) and oropharyngeal symptoms. A logistic multiple regression model revealed that headache was directly associated with D-dimer and creatinine levels, the use of high flow nasal cannula and arthromyalgia, while urea levels, beta-lactamic treatment and hypertension were negatively associated with headache. COVID-19-associated headache characteristics were available in 23/48 (48%) patients. Headache was the onset symptom in 8/20 (40%), of mild or moderate intensity in 17/20 (85%) patients, with oppressive characteristics in 17/18 (94%) and holocranial 8/19 (42%) or temporal 7/19 (37%) localization.
Our results show that headache is associated with a more benign SARS-CoV-2 infection. COVID-19-associated headache appears as an early symptom and as a novel headache with characteristics of headache attributed to systemic viral infection. Further research addressing the underlying mechanisms to confirm these findings is warranted.

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