Findings from a study published in the European Journal of Neurology show that headache was associated with a more benign severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
“We have found that [younger] age and the absence of baseline pathologies such as hypertension, atrial fibrillation and Charlson comorbidities are associated with the presence of headache in hospitalised coronavirus disease 2019 (COVID-19) patients,” wrote Alicia Gonzalez-Martinez, MD, Hospital Universitario de La Princesa, Madrid, Spain, and colleagues. “This indicates that headache may present as a COVID-19 symptom in individuals with healthier backgrounds suggesting that healthy immune systems could have a role in the development of headache.”
The case-control study included 379 patients with COVID-19 who were hospitalised in a tertiary hospital in Madrid in March 2020. Of the patients, 48 (13%) developed headache, with a median age of 57.9 years and 62% were men. The remaining 331 patients who did not develop headache during their hospitalisation were selected as controls.
The researchers found that headache was associated with younger age (P = 0.001), lower Charlson comorbidity index (P = 0.004) and reduced mortality (P = 0.047), as well as with lower levels of C-reactive protein (P = 0.019), mild acute respiratory distress syndrome (ARDS) (P = 0.001) and presence of oropharyngeal symptoms. Furthermore, baseline hypertension (P = 0.005) and atrial fibrillation (P = 0.042) were more prevalent among controls. A logistic multiple regression model revealed that headache was directly associated with D-dimer (P = 0.006) and creatinine (P = 0.008) levels, the use of high flow nasal cannula (P = 0.001) and arthromyalgia, while urea levels (P = 0.016), beta-lactamic treatment (P = 0.001) and hypertension (P = 0.033) were negatively associated with headache.
Meanwhile, COVID-19-associated headache characteristics were available in 23 (48 %) of 48 patients. Of these patients, 20 (87%) patients developed a novel headache during COVID -19.
Headache was of mild or moderate intensity in 17 patients, with oppressive characteristics in 17 patients. Meanwhile, headache with holocranial localisation was reported in 8 patients and temporal localisation in 7 patients. The authors noted that headache was never accompanied by trigeminal autonomic symptoms among the patients.
“COVID-19-associated headache appears as an early symptom and as a novel headache with characteristics of headache attributed to systemic viral infection,” the authors wrote. “Further research addressing the underlying mechanisms to confirm these findings is warranted.”
“Although neurological symptoms have been previously related to COVID-19 severity, headache could be an exception,” the authors noted. “We did not find differences in ICU admission, but multiorgan failure and exitus appear to be less prevalent in patients with headache. These findings are aligned with recent studies showing that headache is associated with a lower risk of mortality due to SARS-CoV-2 infection.”
“Collectively, the results from our case-control study show that the presence of headache is associated with mild inflammation and mild pulmonary alterations and with a better prognosis during COVID -19,” the authors concluded. “Recognising COVID-19-associated headache may help clinicians improve clinical management and treatment of patients with SARS-CoV-2 infection.“