Conference Coverage

Headache is a common post–COVID-19 complaint



Post–COVID-19 headache is a common and sometimes persistent problem. It may take the form of new-onset headache, or exacerbations of preexisting headache conditions such as migraine.

Deena Kuruvilla, MD, director of the Westport (Conn.) Headache Institute

Dr. Deena Kuruvilla

The Centers for Disease Control and Prevention has identified it as a sentinel symptom of COVID-19 disease. “A lot of the recommendations surrounding post-COVID headache is that if you identify a patient who has headaches associated with fever, and myalgia, and other systemic symptoms, the specificity of a COVID-19 diagnosis goes up. So [COVID-19] is a really important feature to look out for in patients with headache,” Deena Kuruvilla, MD, said during a presentation on post–COVID-19 headache at the 2021 Scottsdale Headache Symposium.

Estimates of the prevalence of headache in COVID-19 range widely, from 6.5% to 71%, but Dr. Kuruvilla has plenty of personal experience with it. “During my stint on the inpatient neurology service during the peak of COVID, I saw patients with headache being one of the most frequent complaints, [along with] dizziness, stroke, and seizure among many other neurological manifestations,” said Dr. Kuruvilla, director of the Westport (Conn.) Headache Institute.

One meta-analysis showed that 47% of patients with COVID-19 complain of headache within 30 days of diagnosis, and this drops to around 10% at 60-90 days, and around 8% at 180 days.

A survey of 3,458 patients, published in the Journal of Headache Pain, found that migraine is the most common type of post–COVID-19 headache phenotype, and patients reporting anosmia-ageusia were more likely to have post–COVID-19 headache (odds ratio [OR], 5.39; 95% confidence interval, 1.66-17.45).

A case-control study of post–COVID-19 headache patients with and without a history of migraine found that those with a history of migraine were more likely to have post–COVID-19 symptoms (OR, 1.70; P < .001) and fatigue (OR, 2.89; P = .008). “Interestingly, they found no difference in headache as post-COVID symptoms in people who had a history of migraine compared with people without a history of migraine,” said Dr. Kuruvilla.

Headache and COVID-19: What is the connection?

Several mechanisms have been proposed for direct invasion of the central nervous system, either via infection through the angiotensin-converting enzyme 2 (ACE-2) receptor, which is expressed in brain regions including the motor cortex, the posterior cingulate cortex, and the olfactory bulb, among other locations. Another potential mechanism is direct entry through the olfactory nerve and the associated olfactory epithelium. There are various potential mechanisms for spread among the peripheral nervous system, and the blood-brain barrier can be compromised by infection of vascular endothelial cells. According to the literature, neuronal damage seems to occur directly from viral damage rather than from the immune response, said Dr. Kuruvilla.

The virus may also gain entry to the CNS indirectly, as a result of hypoxia and metabolic disturbances, as well as dehydration and systematic inflammation. The cytokine storm associated with COVID-19 infection can activate C-reactive protein and calcitonin gene-related peptide (CGRP), which plays a key role in migraine pathology. The CGRP receptor antagonist vazegepant is being studied in a phase 2 clinical trial for the treatment of COVID-19–related lung inflammation.


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