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New research suggests headache may be a key symptom of COVID-19 that predicts clinical development in patients.
Findings from an observational study of more than 100 patients show headache onset may occur during the presymptomatic and/or symptomatic phases of COVID-19 progression and sometimes mimics tension or migraine headaches.
Headache is considered a primary symptom of COVID-19. The study of 214 COVID-19 positive patients showed that approximately 13 percent of participants experienced headache and 5 percent experienced anosmia (loss of the sense of smell).
Appearance of headache, itself, was associated with shorter symptomatic periods, while headache in conjunction with anosmia was associated with a shorter hospitalization period for COVID-19 positive patients.
In a subset of participants, headache persisted even after COVID-19 had resolved.
Investigators of the study note that understanding the pathophysiology of headache in COVID-19 could improve understanding of migraine and other headache disorders.
“It seems that those patients who start early on, during the asymptomatic or early symptomatic period of COVID-19, with headache have a more localized inflammatory response that may reflect the ability of the body to better control and respond to the infection by SARS-CoV2,” says lead investigator Patricia Pozo-Rosich, MD, PhD, head of the Headache and Craniofacial Pain Unit at Vall d’Hebron University Hospital. She presented the findings at the American Headache Society (AHS) Annual Meeting 2020, which was held virtually on June 13.
Systemic inflammation
Novel coronavirus SARS-CoV2 penetrates the cells through ACE2 receptors, which exist throughout the body.
“SARS-CoV2 enters the body through the nasal cavity, and it probably penetrates the nervous system in the periphery through afferent branches of the olfactory and trigeminal nerve,” Pozo-Rosich says.
The virus travels to the lungs and, later, enters the bloodstream, which generates systemic inflammation that may turn into a cytokine storm. Research shows identified cortical hyperintensities and olfactory bulb hyperintensities in patients with COVID-19, suggesting that the virus directly infects the central nervous system.
Interleukin-6 (IL-6), one of the main inflammatory molecules, appears related to COVID-19 and because of this, has become a therapeutic target. Levels of IL-6 may be lower and tend to be more stable in patients with both COVID-19 and headache than in patients with COVID-19 only.
Researchers observed 130 patients (51 percent women; mean age, 54 years) with COVID-19 who were attended by neurologists at Vall d’Hebron. Within this group, 74.4 percent of patients experienced headache.
Those with headache tended to be younger than those without headache (mean age, 50 years versus 63 years, respectively) and tended to be women (58.6 percent versus 29.4 percent).
Approximately one-third of patients with headache had a history of migraine. Most patients reported mild to moderate pain that resembled tension-type headache. In those participants with severe pain and migraine-like presentations, headache usually began during the asymptomatic phase of COVID-19.
The headache preceding typical COVID-19 symptoms was distinct from the patients’ usual migraine, alluding to the possibility that headache related to COVID-19 is mechanistically different than migraine.
“It is possible that headache is a manifestation of COVID-19 CNS invasion or cytokine storm, though further data is needed,” Pozo-Rosich said.
The first patient’s headache resolved with resolution of other COVID-19 symptoms, while the second patient continued to have headaches for two weeks after resolution of typical COVID-19 symptoms. Moreover, the first patient did not have migrainous features with her continuous headache.