Epidemiology and clinical characteristics of headache among COVID-19 patients in Lebanon: a retrospective cohort study

The year 2019 witnessed the emergence of a novel Corona virus (COVID-19) in Wuhan, China, leading to a global pandemic by March 2020 [1]. By July 7, 2023, a total of 691 million confirmed COVID-19 cases and 6.9 million deaths were reported [2]. The clinical symptoms of COVID-19 were mainly fever, sore throat, cough, myalgia, fatigue, diarrhea, shortness of breath, and anosmia [1, 3, 4]. In addition, several studies highlighted the neurological manifestations of COVID-19 such as headache, epilepsy, myalgia, and Guillian–Barre syndrome (GBS), encephalitis, anosmia, and others [1, 3, 5]. These neurological symptoms are caused by three main mechanisms. These mechanisms include direct nervous system involvement, immune system-mediated problems, or secondary to a systemic disease or lung damage [6]. A study done in Spain reported that the occurrence of headache reached about 22.7% in patients whose age ranged between 18 and 49 years old [7]. According to the American Headache Society, around 47.1% patients during the acute phase of COVID-19 reported having headache [8].

Many studies focused on the characteristics and location of the headache, whether unilateral/bilateral or diffuse, occipital or fronto-temporal, and the associated symptoms such as photophobia, phonophobia, conjunctival injection, nausea and vomiting [9]. In Lebanon, no studies have been conducting to study the prevalence and characteristics of headache associated with COVID-19 infection. The aim of this study is to recognize the epidemiology, characteristic and progression of headache among patients with COVID-19 in Lebanon.

The study conducted targeted and evaluated the prevalence of headache related to COVID-19.

Although headache is a prominent symptom, studies did not focus on its importance but rather focused on the respiratory, and intensive care aspects that were much more prominent during the course of the disease [12]. For this, the primary focus of this study was to categorize and specify headache intensity, duration, exacerbating factors, and any change in the previous type of headache prior to COVID-19 infection.

Several types of headache has been classified, for which we are going to discuss 3 of them. For instance, migraine is characterized as a stabbing, pulsatile unilateral headache that lasts between 4 h and 3 days. Migraine is often associated with nausea, vomiting, photophobia and phonophobia. Migraine can be familial, or can be associated with hormonal imbalances, psychological disorders, smoking, environmental factors, epilepsy, and others [13].

Cluster headache is another type, characterized as an excruciating unilateral pain of short duration (15 min to 3 h), and associated with autonomic features such as ptosis, lacrimation, rhinorrhea, sweating and conjunctival injection. Cluster headache is more common among males and smokers [13, 14].

Trigeminal neuralgia is characterized by a unilateral electric shock-like pain along the trigeminal nerve branches. It is caused by irritation to the trigeminal nerve, and often stimulated by brushing hair and teeth, smoking, shaving, talking, eating, drinking, or even a light breeze or water splash to the face. Trigeminal headache is more common among females, and can either occur spontaneously, or as a result of head trauma and dental procedures [15].

There are many possible mechanisms of headache related to COVID-19, however, virus invasion through nasal or oral cavity by the trigeminal nerve is the most rational mechanism especially that our results show a close association between headache and loss of taste and smell (68.3%) [3]. The involvement and alteration of angiotensin converting enzyme (ACE2 and ACE) in the regulation of blood pressure can indirectly cause headache as well [16]. Another mechanism could be due to increase in inflammatory cytokines including tumor necrosis factor (TNFa), Interleukins (IL-1, and IL-6) known as the cytokine storm [12, 16, 17]. The headache that appears after the 7th and 10th day of illness are usually provoked by this cytokine storm [12]. In our study, 87% of the participants reported headache in the first week of infection which could be due to viral illness itself and not due to cytokine storm. Infection of cerebral tissue, or intracerebral hypoxia could be other potential causes of headache during COVID-19 infection [16]. However, hypoxia was absent in about 89% of patients in our study.

Many studies reported headache as a clinical manifestations of COVID-19 [5, 12, 17]. In our study, tension headache (62.8%) and migraine (29.5%) were commonly encountered as well. The location of headache in our study shows diffuse involvement (48.7%) predominantly with pressuring character (77%), and only partially relieved with analgesics (54.9%), with a duration of less than 12 h (57%). This is also shown in other studies where pain was mainly moderate to severe bilateral, frontal, and characterized by pressuring quality [4, 5, 7, 17, 18]. Intensity of headache was reported to be equally moderate > 4/10 (38%), to severe > 7/10 (37.8%) in our study. Similarly, a study done showed that 89% of participants reported headache to have an intensity > 5, and 60% having an intensity of > 7/10 in severity [5]. Approximately 53% of participants in our study reported headache initiation during the first 2 days of COVID-19 infection. Other studies reported a more severe course of headache occurring during the 7th and 10th day of infection correlated to the cytokine storm, with the need of analgesic use exceeding 3 days among 72.2% of participants [4, 12]. Although other studies showed a more severe course of headache, only 7.7% of the participants necessitated emergency admission, and 29.4% required a consultation from a physician in our study. The milder symptoms found in our population could be suggested by the possible developed immunity among our participants, as the data were collected 1 year after the pandemic started [19].

About 43% of participants reported a change of the previous headache during or after COVID-19 infection. The changes reported were increasing severity of headache (49.6%), type changed (36.7%), increasing episodes (29.5%), increasing duration (28.8%), and change in response to analgesics (20.9%). A retrospective study published in 2023, showed that headache was one of the earliest neurological symptoms reported among patients with COVID-19, and hence people who had primary headache would experience an increase in severity [20].

There are several other features reported in our study along with headache during COVID-19 such as myalgia (83.1%), loss of taste and smell (68.3%), gastrointestinal symptoms (37.1%), loss of consciousness (12.4%), and nerve injuries (6.9%). These are considered systemic symptoms and were reported in 98% of participants in a study done in Spain [7]. In a study done in Beijing, China, 262 cases reported fever, cough, fatigue, and dyspnea [18]. Another study interestingly confirmed 11.4% COVID-19 cases attributed with gastrointestinal symptoms and showed that 21.62% among them were associated with higher rates of headache compared to patients without gastrointestinal symptoms. This is mainly attributed to the presence of high fever and alteration in electrolyte balance [18]. In addition, participants reported nausea and vomiting (152, 41.8%), photophobia (128, 35.2%), and phonophobia (169, 46.4%) along with COVID-19 headache in our study. These symptoms are also directly correlated with symptoms of migraine. These features are important to consider in order to determine the severity of the illness. Headache that is due to meningitis or encephalitis during the course of illness will be predominantly associated with neck stiffness, nausea and vomiting, light sensitivity, and fever [18]. This proves how headache can play a role in the prognosis and spectrum of COVID-19 disease. Our study showed a low incidence of nerve injuries as well as loss of consciousness associated with headache among participants diagnosed with COVID-19, since the mean age of our patients was 39 years with low frequency of associated medical conditions. Thus, patients who usually complained of headache during COVID-19 did not have a viral central nervous system (CNS) infection, but rather a systemic viral infection in accordance to our study.

Headache is one of the most frequent and primary symptom associated with COVID-19 within the first 2 days of infection. COVID-19-related headache was characterized mainly as diffuse, pressuring, and partially relieved by analgesics. Headache was associated with photophobia, phonophobia and myalgia. Moreover, patients with previous headache reported an increase in pain severity, duration, more frequent episodes and a change in the headache type. Thus, headache should raise early concern of probability of being infected by COVID-19.