By Louise M. Klebanoff, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: Headache is a common feature of acute COVID-19 infection, as well as a long-standing feature of “long COVID” after recovery from the acute infection. Treatment is symptomatic, based on the characteristics of the headache syndrome.
SOURCE: Rocha-Filho PAS. Headache associated with COVID-19: Epidemiology, characteristics, pathophysiology, and management. Headache 2022:62:650-656.
Neurological symptoms are reported commonly in patients with COVID-19, with the most frequent symptoms being headache, anosmia, ageusia, and myalgia. Rocha-Filho wrote a narrative review following a literature search on COVID-19 and headache to further clarify the epidemiology, clinical characteristics, potential pathophysiology, and possible treatments.
Rocha-Filho reported that 47.1% (95% confidence interval, 35.8% to 58.6%) of patients with COVID-19 reported headache in the acute phase of their illness. Headaches were seen more commonly in younger patients; patients with a prior history of primary headache disorders, including migraine; and those with concomitant anosmia, ageusia, and myalgia. There was no consistent gender difference in headache frequency. Headache was not consistently found to be a prognostic indicator for length of hospital stay or for mortality.
Typically, headaches begin in the early symptomatic phase of COVID-19 illness. Headaches were described as bilateral, with tight or pressing pain of moderate intensity consistent with a muscle tension-type headache. However, associated symptoms often seen with migraine, such as photophobia, phonophobia, nausea, and emesis, also were reported. Patients reported that headaches worsened with coughing, moving the head, and moving the eyes.
Several neurological complications of COVID-19, including arterial and venous cerebrovascular disease, encephalitis, and acute disseminated encephalomyelitis, can present with headache. Patients with COVID-19 presenting with headache need to be assessed for red-flag symptoms, such as sudden onset headache, progressively worsening headache, headache accompanied by seizures, or an abnormal neurological examination, which would indicate the need for diagnostic imaging and possible cerebrospinal fluid (CSF) examination to exclude these life-threatening conditions.
The pathophysiology of COVID-19-associated headaches is not well understood. Possible mechanisms include direct viral injury with vascular damage to the olfactory bulbs and inflammation of the nasal cavities, and subsequent activation of the trigeminal system, hypoxemia, dehydration, and systemic inflammation. Several studies have found elevated levels of pro-inflammatory peptides, including serum high mobility group box-1, nod-like receptor pyrin domain-containing 3, interleukin 6, and angiotensin converting enzyme 2, but this has not been found consistently, and the mechanism of action is uncertain.
The treatment of COVID-19-related headache is symptomatic. There have been no clinical trials to assess acute or persistent headache in this patient population. Many patients respond well to simple analgesics, including nonsteroidal anti-inflammatory drugs, acetaminophen, triptans, or a combination of medications. The use of corticosteroids is controversial. Two Egyptian studies reported corticosteroid use in hospitalized patients with COVID-19 and moderate-severe headache and concomitant systemic illness; there was a suggestion that the patients treated with corticosteroids had an improved outcome, but details specifically on headache frequency and severity were absent. A small study of 37 patients with COVID-19-associated headache treated with indomethacin 50 mg twice per day for five days found a 50% reduction in headache severity in 36 patients.
Up to 45% of patients with COVID-19-associated headache in the acute phase of illness will have persistent headache after their systemic illness has resolved. Patients with persistent headache more than six weeks following COVID-19 infection were more likely female, had a history of prior primary headaches, had more persistent systemic symptoms, and reported headache as an initial symptom. In 61% of these patents, the headache was constant and daily. The incidence of chronic headache decreases over time, with headaches persisting for 60 days in 16.5% of patients, 90 days for 10.6% of patients, and more than 180 days in 8.4% of patients.
Like other viruses, COVID-19 can trigger new daily persistent headache, which is challenging to treat. Treatment has not been well studied. Patients are treated based on the clinical characteristics of their headache, with medications used for chronic daily headache, new daily persistent headache, and chronic migraine all tried, with variable results. Anecdotal reports have indicated that amitriptyline, venlafaxine, and onabotulinumtoxin A all can be helpful.
COMMENTARY
This study provides a narrative review of the current literature on COVID-19-associated headache. Headache is a common feature of COVID-19, often a presenting feature, and frequently the symptom that is most troubling to the patient. Although the incidence of chronic headache following acute COVID-19 infection improves over time, a substantial proportion of patients develop chronic daily headaches. These headaches have characteristics of both muscle tension-type headache and migraine. The pathophysiology of COVID-19-associated headache is not well defined. Treatment is symptomatic, with simple analgesics, triptans, and/or daily medication for headache prevention all reported.
Considering the frequency of COVID-19 and the high proportion of patients who develop headaches, additional studies to better define headache frequency and characteristics and controlled studies regarding acute and chronic treatment clearly are needed.
