Red flags concerning prior medical history, including onset of headache after 50 years, a history of cancer, and presence of immunocompromise, were present in almost all patients with coronavirus disease 2019 (COVID-19) who developed headache, according to a study in Headache.

Study researchers from Spain sought to assess the frequency of main red flags in patients with COVID-19 who developed headache. In this observational, cross-sectional study, they assessed the frequency and types of red flags in 576 consecutive hospitalized patients with confirmed COVID-19. A final total of 104 patients who described headache during the course of their disease were included in the study (63.5% women; mean age, 56.7 years). A headache expert conducted a structured interview to determine the presence and type of key red flags.

The red flags regarding prior medical history included headache onset after 50 years of age, current or prior cancer history, and the presence of an immunocompromised state. Concerning the headache, red flags included thunderclap onset, recent headache onset that coincided or immediately preceded the onset of COVID-19 symptoms, change in headache pattern among those with pre-existent headache, treatment resistance, sleep interruption, and worst headache ever experienced among several others.

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There was at least 1 abnormal laboratory finding in 94.2% (n=98) of patients, with abnormal C-reactive protein being the most common (84%). 76% (n=79) of patients with COVID-19 and headache reported red flags concerning prior medical history. Red flags regarding the headache were present in 95.2% (n=99) of patients. Other common red flags included fever (89.4%) and cough (85.6%). Systemic symptoms were described in all patients, whereas neurologic symptoms were reported in 82.7% (n=86) of patients. None of the patients reported any speech disorder, visual disturbances, focal weakness, ataxia, seizures, or hypoesthesia.

A limitation of this study was selection bias due to the the strict inclusion of only patients who were hospitalized. Consequently, the disease may have been more severe in these patients.  Study researchers additionally emphasized the need to evaluate the sensitivity of red flags.

The investigators concluded that while red flags were common, they found no single universal red flag in these patients, reinforcing “how important the anamnesis is, and in particular in headache medicine.”


García-Azorín D, Trigo J, Talavera B, et al. Frequency and type of red flags in patients with Covid-19 and headache: A series of 104 hospitalized patients. Headache. Published online August 13, 2020. doi:10.1111/head.13927