• Amir Soheil Tolebeyan, Niushen Zhang, Vanessa Cooper, and Deena E Kuruvilla.
• Fellow in Headache and Facial Pain, Department of Neurology, Yale School of Medicine, New Haven, CT, USA.
• Headache. 2020 Nov 1; 60 (10): 2131-2138.

ObjectiveTo summarize available literature regarding headache as a manifestation of coronaviruses and to describe potential underlying mechanisms.Review MethodsReferences for this review were identified by searches within PubMed without any date restrictions. The search terms used were coronavirus disease 2019 (COVID-19) clinical manifestation, COVID-19 epidemiology, neurologic findings in COVID-19, headache in COVID-19, neurologic manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and headache in SARS-CoV-2.ResultsHeadache is one of the most common neurologic complaints in patients with SARS-CoV-2. While the pathophysiological connection between headache and SARS-CoV-2 is unclear, inflammatory mechanisms may play a key role. One of the mechanisms cited in the literature of migraine and other headache disorders is the activation of nociceptive sensory neurons by cytokines and chemokines. A similar mechanism has been reported in SARS-CoV-2 with the release of cytokines and chemokines by macrophages throughout the course of infection. Other mechanisms for headache in SARS-CoV-2 include (1) viral neuroinvasion as seen with viral encephalitis; (2) hypoxemia due to the well-described pulmonary manifestations of the disease; and (3) thrombosis secondary to COVID-19 induced hypercoagulable states.ConclusionAccording to the Centers for Disease Control, common symptoms of human coronavirus include fever, cough, runny nose, sore throat, and headache. In the case of SARS-CoV-2, there are limited reports about headaches, one of the most common clinical manifestations. There are currently no studies that focus specifically on headache among patients with SARS-CoV-2 infection.© 2020 American Headache Society.

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