Research Summary: Headache associated with COVID-19: Epidemiology, characteristics, pathophysiology, and management

COVID-19 has had an effect on virtually every area of a person’s life, but there are some effects that are more prominent than others based on that person’s health background. For those with secondary headache, the question is: What is the relationship between complications of COVID-19 and the epidemiology, pathophysiology, characteristics, and management of secondary headache? Continue reading to learn more about a new study on the issue and its findings.

Study Overview

• In this narrative literature review, the authors report on the epidemiology, pathophysiology, characteristics, and management of secondary headache associated with complications of COVID-19. Researchers found that headache is a clinically significant symptom of COVID-19 and that COVID-19 can trigger daily persistent headache in some patients.
• Neurological symptoms are frequently reported by patients with COVID-19, with 14-19% of patients who present with headache reporting this symptom bothers them the most. 

Study Results

Epidemiology of Headache in COVID-19

• Headache is reported in 47.1% (95% CI 35.8-58.6%) of patients in the acute phase of COVID-19.
• Frequency varies with the severity of COVID-19, with higher frequency in outpatients versus hospitalized patients.
• Headache as a symptom of COVID-19 is more common in younger people; in those with previous primary headache or migraine; and in those who present with accompanying anosmia, ageusia, and myalgia.

Characteristics of headache in the acute phase of COVID-19

• Headache begins the first day of illness in 39-55% of patients and is the first symptom in 6-29% of patients. In some cases, it may be the only symptom of COVID-19.
• For 47-80% of patients, the headache pattern experienced with COVID-19 is reportedly different from previous headache patterns.
• Pain is usually bilateral, moderate to severe in intensity, and most frequently has characteristics of tension-type headache or migraine.
• Headache triggered by coughing was observed at a frequency of 2-16%.

Secondary headache associated with complications of COVID-19

• The most common neurological complications of COVID-19 for which headache is a symptom are venous cerebrovascular disease, encephalitis, and acute disseminated encephalomyelitis.
• Cerebral venous sinus thrombosis incidence was 0.8 cases per 1000 hospitalized patients.
• A case series reported 5 out of 25 patients with COVID-19 who underwent CSF examination for refractory headache had intracranial hypertension; four of the patients were women, and four had no papilledema.

Pathophysiology

• Possible mechanisms include direct viral injury or vascular injury, local inflammatory process, hypoxemia, dehydration, and possibly a systemic inflammatory response to infection.

Management of headache

• No clinical trials exist that assess the treatment of headache in the acute phase of COVID-19.
• The most used medications for headache in the acute phase of COVID-19 are acetaminophen, NSAIDs, metamizole, triptans, or a combination of these (25%).
• A case series described six patients whose headache improved after sphenopalatine ganglion block.

Persistence of headache after the acute phase of COVID-19

• Headache persists beyond the acute phase in 6-45% of patients, although headache prevalence may decrease over time.
• One study showed patients who still had headache 6 weeks after the acute stage were more often women, were more likely to have had previous headaches, had more persistent symptoms, more often had headache as a first symptom, and were less responsive to acute pain management; 61% had daily and constant headaches.
• A systematic review found headache persisted up to 60 days in 16.5%, 90 days in 10.6%, and 180 days in 8.4%.
• A different study showed headache prevalence at 1 month was 31%, at 3 months was 19%, at 6 months was 16.8%, and at 9 months was 16%.
• Some patients may develop new daily persistent headache (NDPH), which is a headache that becomes unremitting within 24 hours of onset and persists for at least 3 months.

Implications for Primary Care Clinicians

• Headache is frequently associated with COVID-19 and often has a phenotype similar to tension-type headache or migraine.
• Treatment in the acute phase is based on the headache characteristics and may include common analgesics, migraine-specific acute treatments, or a combination of these.
• Headaches may persist after the acute phase of COVID-19 but typically improve over time.
• Headache may be associated with several neurological complications of COVID-19. Therefore, if a neurological complication is suspected based on the patient’s history and physical exam, or if the patient has developed NDPH, further testing should be considered.
• In patients who develop NDPH, there are case reports of successful treatment with venlafaxine, amitriptyline and onabotulinumtoxinA, and IV followed by oral corticosteroids.

This summary is part of the First Contact — Headache in Primary Care initiative, an American Headache Society program that provides educational resources to empower healthcare professionals and improve headache and migraine care. We encourage providers in all stages of their careers to visit our homepage to access educational tools to improve patient care.