Abstract
Headache is prevalent in coronavirus disease 2019 (COVID-19) patients. The main objective of this study was to compare the characteristics of COVID-19-associated headache to non-COVID-19 headache. The quality-of-life (QoL) and its associated determinants between COVID-19 and non-COVID-19 patients were also compared. A cross-sectional study was conducted in Banda Aceh, Indonesia. Headache and QoL were assessed using the International Classification of Headache Disorders, version 3 (ICHD-3), and the 36-item Short Form Health Survey (SF-36), respectively. Factors associated with poor QoL in COVID-19 and non-COVID-19 patients were examined using logistic regression. A total of 356 headache patients were included: 215 COVID-19 and 141 non-COVID-19 patients. Our data suggested that the headache in COVID-19 patients was bilateral; pain centered on one specific area with a pulsating or pressing sensation; pain intensity ranging from moderate to severe; and the frequency ranging from more than twice per week to every day. Non-COVID-19 headache was bilateral; pain centered on one side of the head resembling a migraine with pulsating or pressing sensation; mild to moderate pain intensity; and the frequency of one or two times per month. In COVID-19, low QoL was associated with unemployment status, having non-health-related jobs, having used painkillers to reduce the pain, having long duration of headache, having more frequency of attacks, and having headaches that were worsened by activities or light, and having additional symptom during a headache attach. In non-COVID-19 patients, poor QoL was associated with the use of painkillers, long duration of headache, and having conditions that aggravate the headache. To prevent long-term effects of headache associated with COVID-19, studies exploring the photobiology of headache are needed, along with the necessity of having standardised guideline on headache prevention.
Keywords: COVID-19, headache, post-COVID-19 symptom, quality-of-life, long-COVID
Introduction
The pandemic of the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more 587 million people and resulted in over 6 million deaths as of 15 August 2022 [1]. Headache, along with shortness of breath and coughing are among the early symptoms of SARS-CoV-2 infection [2] and the most common neurological complaint in COVID-19 patients [3, 4]. The prevalence of headache ranges from 14 to 60% in COVID-19 patients [3-7]. The symptoms of headache vary in COVID-19 patients, including pain throughout the head and a pinching sensation to heaviness on the top of the head [3, 8, 9].
Headache is also reported in recovered COVID-19 individuals. Headache is also the most common neurological symptom in individual with long COVID-19, along with other complaints such as impaired concentration and memory [2, 10-13]. Mendelson et al. proposed that a headache that lasts at least six months, whether as a single clinical symptom, co-occurring with other cognitive disorders such as "brain fog" or exacerbating pre-existing migraine symptoms should be suspected of being caused by long COVID-19 [14]. Headache in long COVID-19 patients may be triggered by preexisting headache activation or by genetic predispositions to migraine [13].
A study found that headache as an acute phase symptom was more frequent in non-hospitalized patients than hospitalized patients (57.9% vs 31.1%) [15]. Another study reported no statistically significant difference in headache prevalence between severe and mild COVID-19 patients, recovered vs non-recovered patients, or between patients in intensive care units (ICU) vs non-ICU [16]. The prevalence of headache in COVID-19 patients is double when compared to individuals without COVID-19 [17, 18]; moreover, 72% of patients with COVID-19 stated that the headache experienced was different during and before infection [19].
Studies comparing the characteristics of headaches in patients with and without COVID-19 are limited. Hence, the aim of this study was to compare the characteristics of headache between COVID-19 and non-COVID-19 patients. Another goal was to compare the quality-of-life (QoL) between these groups and to explore possible determinants of poor QoL.
Methods
Study design and participants
A cross-sectional study was conducted from February to June 2022 at the Department of Neurology of Dr. Zainoel Abidin Hospital, a provincial referral hospital in Aceh Province of Indonesia. Patients were aged 18-year-old or older and came to the Department of Neurology with headache complains, both with and without a history of COVID-19 infection. COVID-19 infection was confirmed with SARS-CoV-2 polymerase chain reaction (PCR). Those who agreed to participate were interviewed. Information related to the characteristics of the headache, clinical symptoms, the history of COVID-19 and QoL were collected.
Study variables and data collection
This study collected the following information: (1) demographic data, including the history of COVID-19 vaccination; (2) headache characteristics; and (3) the assessment of QoL. Headache in COVID-19 and non-COVID-19 groups were diagnosed according to the headache characteristics by the International Classification of Headache Disorders, version 3 (ICHD-3) [20]. Headache-related questions consisted of: (1) first time of headache occurred; (2) headache characteristics, included: (a) location, (b) duration of attack, (c) frequency, (d) sensation, and (e) severity (score 0 or no pain; score 1–3 or mild pain; score 4–6 or moderate pain; score 7–9 or severe pain; score 10 or very severe pain); (3) additional symptoms during the headache attack (photophobia, phonophobia, nausea/vomiting); and (4) whether they have to take an analgesic, abortive, or prophylactic medication when the headache occurred. More details about the headache-related questions have been published elsewhere [22].
The QoL of each patient was measured using a 36-item instrument, the Short Form Health Survey (SF-36) [21]; a full description of these questions is provided elsewhere [22]. By adopting a cut-off point of 50%, levels of QoL were classified into good or poor.
Statistical analysis
All analyses were conducted in SPSS v.22 (IBM, Armonk, New York, US). The Shapiro-Wilk test was used to determine the normality of data, which was described as mean and standard deviation (SD). Frequency (n) and percentage (%) were used to describe the sample. The Student t-test was used to compare variables between the two study groups (COVID-19 vs non-COVID-19 patients). To compare the demographic and headache characteristics between COVID-19 and non-COVID-19 patients, the Chi-square test or Fisher's exact test were used. Logistic regression analysis was performed to assess the predictors of headaches. A p value of ≤0.05 was considered to be statistically significant in the analyses.
Results
Sociodemographic characteristics
In the final analysis, we included 356 headache patients (215 COVID-19 and 141 non-COVID-19). The demographic characteristics of the patients from both groups are presented in Table 1. More than half of patients in both categories had been vaccinated, with 1st and 2nd dose, against COVID-19; the frequency of non-COVID-19 patients was slightly higher when compared to COVID-19 patients (83.7% vs 62.8% and 78.7% vs 60.9% for the 1st and 2nd dose, respectively).
Table 1. Patients’ characteristics (n=356).
| Questions | COVID-19 | Non-COVID-19 | ||
|---|---|---|---|---|
| n | % | n | % | |
| Have received the 1st dose of COVID-19 vaccine | ||||
| No | 80 | 37-2 | 23 | 16.3 |
| Yes | 135 | 62.8 | 118 | 83.7 |
| Have received the 2nd dose of COVID-19 vaccine | ||||
| No | 84 | 39-1 | 30 | 21.3 |
| Yes | 131 | 60.9 | 111 | 78.7 |
| Have received a booster dose of COVID-19 vaccine | ||||
| No | 177 | 82.3 | 77 | 54.6 |
| Yes | 38 | 17.7 | 64 | 45.5 |
| Age group (year) | ||||
| 20-29 | 55 | 25.6 | 70 | 49.6 |
| 30-39 | 98 | 45.6 | 48 | 34.0 |
| 40-49 | 41 | 19.1 | 11 | 7.8 |
| >50 | 21 | 9.8 | 12 | 8.5 |
| Gender | ||||
| Male | 65 | 30.2 | 56 | 39.7 |
| Female | 150 | 69.8 | 85 | 60.3 |
| Employment status | ||||
| Unemployed | 47 | 21.9 | 47 | 33.3 |
| Employed | 168 | 78.1 | 94 | 66.7 |
| Health-related workers | ||||
| No | 76 | 35.3 | 64 | 45.4 |
| Yes | 139 | 64.7 | 77 | 54.6 |
| Monthly income (Indonesian Rupiah) | ||||
| <3 million | 46 | 21.4 | 50 | 35.5 |
| 3-5 million | 112 | 52.1 | 46 | 32.6 |
| 5-10 million | 45 | 20.9 | 34 | 24.1 |
| >10 million | 12 | 5.6 | 11 | 7.8 |
In both COVID-19 and non-COVID-19 patients, more than half have not received a booster dose of vaccination. The COVID-19 group was mostly aged between 30–39, while non-COVID-19 patients were predominantly aged 20–29-year-old (Table 1). Women outnumbered men in both categories (69.8% and 60.3%, respectively). Approximately 21% and 35% of COVID-19 and non-COVID-19 groups earned less than 3 million Indonesian Rupiah (IDR) per month (equal to 190 $US as per November 2022 currency rate) (Table 1).
Comparison of headache characteristics between COVID-19 and non-COVID-19 groups
Over 71% of COVID-19 patients required pain killers to relieve their headaches, whereas more than half of non-COVID-19 patients did not (Table 2). The most reported location of headaches by both groups was throughout the head (47.4% vs 39.0%); approximately 20% was unable to describe where the pain was located. The headache of both groups was in the different locations. The percentage of patients who complained of headache only occurring at one point or area was different between COVID-19 and non-COVID-19 groups (16.7% vs 2.1%).
Table 2. Headache characteristics between COVID-19 vs non-COVID-19 patients (n=356).
| Characteristics | COVID-19 | Non-COVID-19 | p-value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Had taken painkillers for the headache | <0.001** | ||||
| No | 61 | 28.4 | 80 | 56.7 | |
| Yes | 154 | 71.6 | 61 | 43.3 | |
| Location | 0.001** | ||||
| Only in one point/area | 36 | 16.7 | 3 | 2.1 | |
| Right side | 20 | 9.3 | 25 | 17.7 | |
| Left side | 11 | 5.1 | 25 | 17.7 | |
| Whole head | 102 | 47.4 | 55 | 39.0 | |
| Cannot be described | 46 | 21.4 | 33 | 23.4 | |
| Duration (hour) | 0.096 | ||||
| Less than l | 134 | 62.3 | 86 | 61.0 | |
| 1-6 | 68 | 31.6 | 40 | 28.4 | |
| 7-12 | 4 | 1.9 | 10 | 7.1 | |
| More than 12 | 9 | 4.2 | 5 | 3.5 | |
| Frequency | <0.001** | ||||
| 1-2 times/month | 96 | 44.7 | 98 | 69.5 | |
| 1-2 times/week | 32 | 14.9 | 31 | 22.0 | |
| >2 times or more/week | 87 | 40.5 | 12 | 8.5 | |
| Characteristic | <0.001** | ||||
| Pulsating | 132 | 61.4 | 44 | 31.2 | |
| Pressing | 45 | 20.9 | 51 | 36.2 | |
| Fiery | 4 | 1.9 | 29 | 20.6 | |
| Stabbing | 11 | 5.1 | 1 | 0.7 | |
| Combination of 2 characteristics | 20 | 9.3 | 10 | 7.1 | |
| Combination of 3 or 4 characteristics | 3 | 1.4 | 6 | 4.3 | |
| Severity (on a pain scale of 0-10, where 0 is no pain and 10 is very painful) | 0.002** | ||||
| 0 | 3 | 1.4 | 5 | 3.5 | |
| 1-3 | 88 | 40.9 | 80 | 56.7 | |
| 4-6 | 100 | 46.5 | 50 | 35.5 | |
| 7-9 | 22 | 10.2 | 4 | 2.8 | |
| 10 | 2 | 0.9 | 2 | 1.4 | |
| What makes the headache worse | 0.012* | ||||
| None | 56 | 26.0 | 23 | 16.3 | |
| Activity | 97 | 45.1 | 76 | 53.9 | |
| Light | 10 | 4.7 | 13 | 9.2 | |
| Noise | 15 | 7.0 | 7 | 5.0 | |
| Activity and light | 4 | 1.9 | 5 | 3.5 | |
| Activity and noise | 20 | 9.3 | 3 | 2.1 | |
| Light and noise | 4 | 1.9 | 3 | 2.1 | |
| All three (activity, light and noise) | 9 | 4.2 | 11 | 7.8 | |
| What makes the headache better | <0.001** | ||||
| None | 24 | 11.2 | 10 | 7.1 | |
| Rest | 76 | 35.3 | 82 | 58.2 | |
| Painkiller | 43 | 20.0 | 21 | 14.9 | |
| Rest and painkiller | 72 | 33.5 | 28 | 19.9 | |
| Additional symptom during headache | 0.115 | ||||
| No | 116 | 54.0 | 88 | 62.4 | |
| Yes | 99 | 46.0 | 53 | 37.6 | |
*Statistically significant at p<0.05
**Statistically significant at p<0.01
The average headache duration was less than one hour, with no difference in headache duration between COVID-19 and non-COVID-19 groups (62.3% vs. 61%) (Table 2). However, those suffering from COVID-19 had a higher frequency of headaches (>2 times or more per week or almost every day) (40.5%), while in non-COVID-19 group the headaches generally occurred 1–2 times per month (69.5%).
The majority of COVID-19 patients (61.4%) described their headache as pulsating, while 20.9% described it as a pressing sensation. The non-COVID-19 patients, on the other hand, described it as fiery, in addition to pulsating and pressing sensation (20.6%, 31.2%, and 36.2%, respectively). COVID-19 patients experienced headache moderate pain (46.5%), while non-COVID-19 patients experienced mild pain (56.7%). In both COVID-19 and non-COVID-19 patients, having activities/being tired was a factor that worsened headaches, while resting, taking pain killers, or a combination of resting and taking pain killers reduced the pain (Table 2).
Data suggested that the severity (indicated by having taken painkillers and the headache severity score), location, frequency, factors that made headaches worse or better, and the type of symptom during headache were significantly different between COVID-19 and non-COVID-19 patients (Table 2).
Quality-of-life between of the patients
Data indicated that the pain, emotional well-being, and general health were significantly different between COVID-19 and non-COVID-19 patients, with p<0.001, p<0.001, p=0.030, respectively (Table 3).
Table 3. Mean scores of quality-of-life domains between COVID-19 and non-COVID-19 patients (n=356).
| QoL domain | Mean | ± SD | p-value |
|---|---|---|---|
| COVID-19 | Non-COVID-19 | ||
| Physical functioning | 205.58 ± 139.31 | 209.22 ± 151.61 | 0.778 |
| Role limitations due to physical health | 675.12 ± 225.11 | 697.80 ± 248.78 | 0.244 |
| Role limitations due to emotional problems | 186.98 ± 103.30 | 190.07 ± 111.68 | 0.601 |
| Pain | 112.35 ± 41.01 | 132.02 ± 40.11 | <0.001** |
| Energy/fatigue | 180.00 ± 55.30 | 172.06 ± 56.11 | 0.102 |
| Emotional well-being | 553.21 ± 111.63 | 488.87 ± 126.18 | <0.001** |
| Social functioning | 134.88 ± 41.84 | 128.65 ± 40.80 | 0.305 |
| General health | 328.26 ± 95.40 | 310.62 ± 87.11 | 0.030* |
| Total quality of life | 2254.05 ± 531.53 | 2212.00 ± 559.99 | 0.495 |
*Statistically significant at p<0.05
**Statistically significant at p<0.01
The QoL in COVID-19 and non-COVID-19 patients with headache are presented in Table 4. The three domains of QoL (pain, emotional well-being, and social functioning) were significantly different between COVID-19 and non-COVID-19 groups (all p<0.001). Non-COVID-19 patients had a slightly better QoL than COVID-19 patients in the pain domain (35.5% vs 17.7%), while COVID-19 participants had a slightly better QoL regarding emotional well-being and social functioning domains (38.1% vs 20.6% and 55.3% vs 36.2%, respectively) (Table 4).
Table 4. Quality of life between COVID-19 and non-COVID-19 patients (n=356).
| Domain | COVID-19 | Non-COVID-19 | p-value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Physical functioning | 0.484 | ||||
| Good | 88 | 40.9 | 63 | 44.7 | |
| Poor | 127 | 59.1 | 78 | 55.3 | |
| Role limitations due to physical health | 0.235 | ||||
| Good | 99 | 46.0 | 74 | 52.5 | |
| Poor | 116 | 54.0 | 67 | 47.5 | |
| Role limitations due to emotional problems | 0.250 | ||||
| Good | 74 | 34.4 | 57 | 40.4 | |
| Poor | 141 | 65.6 | 84 | 59.6 | |
| Pain | <0.001** | ||||
| Good | 38 | 17.7 | 50 | 35.5 | |
| Poor | 177 | 82.3 | 91 | 64.5 | |
| Energy/fatigue | 0.625 | ||||
| Good | 41 | 19.1 | 24 | 17.0 | |
| Poor | 174 | 80.9 | 117 | 83.0 | |
| Emotional well-being | <0.001** | ||||
| Good | 82 | 38.1 | 29 | 20.6 | |
| Poor | 133 | 61.9 | 112 | 79.4 | |
| Social functioning | <0.001** | ||||
| Good | 119 | 55.3 | 51 | 36.2 | |
| Poor | 96 | 44.7 | 90 | 63.8 | |
| General health | 0.772 | ||||
| Good | 25 | 11.6 | 15 | 10.6 | |
| Poor | 190 | 88.4 | 126 | 89.4 | |
| Total quality-of-life | 0.720 | ||||
| Good | 71 | 33.0 | 44 | 31.2 | |
| Poor | 144 | 67.0 | 97 | 68.8 | |
*Statistically significant at p<0.05
**Statistically significant at p<0.01
Factors associated with patients’ quality-of-life
Unemployment and having a non-health-related work were associated with poor QoL in COVID-19 patients (OR: 0.28; 95%CI: 0.12–0.67, p=0.004 and OR: 0.22; 95%CI: 0.11–0.46, p<0.001, respectively). Other demographic data, such as age, gender, and monthly income, were not associated with QoL in COVID-19 patients (Table 5). In non-COVID-19 patients, none of the sociodemographic characteristics were associated with poor QoL.
Table 5. Factors associated with quality-of-life (good vs poor) in COVID-19-associated headache and non-COVID-19 headache.
| Factor | COVID-19-associated headache | Non-COVID-19 headache | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| n | % | Poor QoL n (%) | OR (95%CI) | p-value | n | % | Poor QoL n (%) | OR (95%CI) | p-value | |
| Age group (year) | ||||||||||
| 20-29 (Reference group (R) | 55 | 25.6 | 39 (70.9) | 1 | 70 | 49.6 | 46 (65.7) | 1 | ||
| 30-39 | 98 | 45.6 | 60 (61.2) | 0.65 (0.32-1.32) | 0.230 | 48 | 34.0 | 32 (66.7) | 1.04 (0.48-2.27) | 0.915 |
| 40-49 | 41 | 19.1 | 27 (65.9) | 0.79 (0.33-1.89) | 0.597 | 11 | 7.8 | 8 (72.7) | 1.39 (0.34-5.73) | 0.648 |
| >50 | 21 | 9.8 | 18 (85.7) | 2.46 (0.64-9.53) | 0.192 | 12 | 8.5 | 11 (91.7) | 5.74 (0.70-47.14) | 0.104 |
| Gender | ||||||||||
| Male (R) | 65 | 30.2 | 39 (60.0) | 1 | 56 | 39.7 | 39 (69.6) | 1 | ||
| Female | 150 | 69.8 | 105 (70.0) | 1.56 (0.85-2.85) | 0.154 | 85 | 60.3 | 58 (68.2) | 0.94 (0.45-1.94) | 0.860 |
| Employment | ||||||||||
| Unemployed (R) | 47 | 21.9 | 40 (85.1) | 1 | 47 | 33.3 | 30 (63.8) | 1 | ||
| Employed | 168 | 78.1 | 104 (61.9) | 0.28 (0.12-0.67) | 0.004** | 94 | 66.7 | 67 (71.3) | 1.41 (0.67-2.96) | 0.369 |
| Health-related worker | ||||||||||
| No (R) | 76 | 35.3 | 65 (85.5) | 1 | 64 | 45.4 | 43 (67.2) | 1 | ||
| Yes | 139 | 64.7 | 79 (56.8) | 0.22 (0.11-0.46) | <0.001** | 77 | 54.6 | 54 (70.1) | 1.15 (0.56-2.34) | 0.707 |
| Monthly income (Indonesian Rupiah) | ||||||||||
| <3 million (R) | 46 | 21.4 | 29 (63.0) | 1 | 50 | 35.5 | 35 (70.0) | 1 | ||
| 3-5 million | 112 | 52.1 | 74 (66.1) | 1.14 (0.56-2.33) | 0.717 | 46 | 32.6 | 28 (60.9) | 0.67 (0.29-1.55) | 0.348 |
| 5-10 million | 45 | 20.9 | 33 (73.3) | 1.61 (0.66-3.93) | 0.294 | 34 | 24.1 | 23 (67.6) | 0.90 (0.35-2.29) | 0.819 |
| >10 million | 12 | 5.6 | 8 (66.7) | 1.17 (0.31-4.48) | 0.816 | 11 | 7.8 | 11 (100.0) | 7x10s (0.00-NA) | 0.999 |
| Had painkillers for the headache | ||||||||||
| No (R) | 61 | 28.4 | 29 (47.5) | 1 | 80 | 56.7 | 49 (61.3) | 1 | ||
| Yes | 154 | 71.6 | 115 (74.7) | 3.25 (1.75-6.05) | <0.001** | 61 | 43.3 | 48 (78.7) | 2.34 (1.09-5.00) | 0.029* |
| Location | ||||||||||
| Only in one point/area (R) | 36 | 16.7 | 15 (41.7) | 1 | 3 | 2.1 | 2 (66.7) | 1 | ||
| Right side | 20 | 9.3 | 13 (65.0) | 2.60 (0.84-8.07) | 0.098 | 25 | 17.7 | 20 (80.0) | 2.00 (0.15-26.73) | 0.600 |
| Left side | 11 | 5.1 | 9 (81.8) | 6.30 (1.19-33.44) | 0.031* | 25 | 17.7 | 19 (76.0) | 1.58 (0.12-20.69) | 0.726 |
| Whole head | 102 | 47.4 | 74 (72.5) | 3.70 (1.68-8.17) | 0.001** | 55 | 39.0 | 36 (65.5) | 0.95 (0.08-11.13) | 0.966 |
| Cannot be described | 46 | 21.4 | 33 (71.7) | 3.55 (1.41-8.94) | 0.007** | 33 | 23.4 | 20 (60.6) | 0.77 (0.06-9.37) | 0.837 |
| Duration (hour) | ||||||||||
| Less than 1 (R) | 134 | 62.3 | 78 (58.2) | 1 | 86 | 61.0 | 49 (57.0) | 1 | ||
| 1-6 | 68 | 31.6 | 56 (82.4) | 3.35 (1.64-6.83) | 0.001** | 40 | 28.4 | 33 (82.5) | 3.56 (1.42-8.94) | 0.007** |
| 7-12 | 4 | 1.9 | 2 (50.0) | 0.72 (0.10-5.25) | 0.744 | 10 | 7.1 | 10 (100.0) | 1X109 (0.00-NA) | 0.999 |
| More than 12 | 9 | 4.2 | 8 (88.9) | 5.74 (0.70-47.23) | 0.104 | 5 | 3.5 | 5 (100.0) | 1X109 (0.00-NA) | 0.999 |
| Frequency | ||||||||||
| 1-2 times/month (R) | 96 | 44.7 | 51 (53.1) | 1 | 98 | 69.5 | 63 (64.3) | 1 | ||
| 1-2 times/week | 32 | 14.9 | 21 (65.6) | 1.68 (0.73-3.87) | 0.219 | 31 | 22.0 | 24 (77.4) | 1.91 (0.75-4.87) | 0.178 |
| >2 times or more | 87 | 40.5 | 72 (82.8) | 4.24 (2.13-8.41) | <0.001** | 12 | 8.5 | 10 (83.3) | 2.78 (0.58-13.40) | 0.203 |
| Characteristic of the headache | ||||||||||
| Pulsating (R) | 132 | 61.4 | 85 (64.4) | 1 | 44 | 31.2 | 26 (59.1) | 1 | ||
| Pressing | 45 | 20.9 | 27 (60.0) | 0.83 (0.41-1.66) | 0.598 | 51 | 36.2 | 39 (76.5) | 2.25 (0.93-5.44) | 0.072 |
| Fiery | 4 | 1.9 | 2 (50.0) | 0.55 (0.08-4.05) | 0.560 | 29 | 20.6 | 17 (58.6) | 0.98 (0.38-2.54) | 0.968 |
| Stabbing | 11 | 5.1 | 10 (90.9) | 5.53 (0.69-44.54) | 0.108 | 1 | 0.7 | 1 (100.0) | 1X109 (0.00-NA) | 1.000 |
| Combination of 2 characteristics | 20 | 9.3 | 17 (85.0) | 3.13 (0.87-11.25) | 0.080 | 10 | 7.1 | 10 (100.0) | 1X109 (0.00-NA) | 0.999 |
| Combination of 3 or 4 characteristics | 3 | 1.4 | 3 (100.0) | 9x10s (0.00-NA) | 0.999 | 6 | 4.3 | 4 (66.7) | 1.39 (0.23-8.38) | 0.723 |
| Severity (on a pain scale of 0-10, where 0 is no pain and 10 is very painful) | ||||||||||
| 0 (R) | 3 | 1.4 | 0 (0.0) | 1 | 5 | 3.5 | 5 (100.0) | 1 | ||
| 1-3 | 88 | 40.9 | 49 (55.7) | 2X109 (0.00-NA) | 0.999 | 80 | 56.7 | 48 (60.0) | 0.00 (0.00-NA) | 0.999 |
| 4-6 | 100 | 46.5 | 75 (75.0) | 5x109 (0.00-NA) | 0.999 | 50 | 35.5 | 39 (78.0) | 0.00 (0.00-NA) | 0.999 |
| 7-9 | 22 | 10.2 | 18 (81.8) | 7x109 (0.00-NA) | 0.999 | 4 | 2.8 | 3 (75.0) | 0.00 (0.00-NA) | 0.999 |
| 10 | 2 | 0.9 | 2 (100.0) | 3X1018 (0.00-NA) | 0.999 | 2 | 1.4 | 2 (100.0) | 1.00 (0.00-NA) | 1.000 |
| What makes the headache worse | ||||||||||
| None(R) | 56 | 26.0 | 29 (51.8) | 1 | 23 | 16.3 | 11 (47.8) | 1 | ||
| Activity | 97 | 45.1 | 66 (68.0) | 1.98 (1.01-3.90) | 0.047* | 76 | 53.9 | 50 (65.8) | 2.10 (0.82-5.40) | 0.125 |
| Light | 10 | 4.7 | 4 (40.0) | 0.62 (0.16-2.44) | 0.495 | 13 | 9.2 | 11 (84.6) | 6.00 (1.08-33.32) | 0.041* |
| Noise | 15 | 7.0 | 13 (86.7) | 6.05 (1.25-29.33) | 0.025 | 7 | 5.0 | 6 (85.7) | 6.55 (0.68-63.33) | 0.105 |
| Activity and light | 4 | 1.9 | 4 (100.0) | 2X109 (0.00-NA) | 0.999 | 5 | 3.5 | 3 (60.0) | 1.64 (0.23-11.70) | 0.624 |
| Activity and noise | 20 | 9.3 | 18 (90.0) | 8.38 (1.78-39.56) | 0.007** | 3 | 2.1 | 3 (100.0) | 2X109 (0.00-NA) | 0.999 |
| Light and noise | 4 | 1.9 | 4 (100.0) | 2x109 (0.00-NA) | 0.999 | 3 | 2.1 | 3 (100.0) | 2X109 (0.00-NA) | 0.999 |
| All three (activity, light and noise) | 9 | 4.2 | 6 (66.7) | 1.86 (0.42-8.19) | 0.411 | 11 | 7.8 | 10 (90.9) | 10.91 (1.19-99.69) | 0.034* |
| What makes the headache better | ||||||||||
| None(R) | 24 | 11.2 | 15 (62.5) | 1 | 10 | 7.1 | 7 (70.0) | 1 | ||
| Rest | 76 | 35.3 | 48 (63.2) | 1.03 (0.40-2.66) | 0.954 | 82 | 58.2 | 49 (59.8) | 0.64 (0.15-2.64) | 0.534 |
| Painkiller | 43 | 20.0 | 29 (67.4) | 1.24 (0.44-3.53) | 0.683 | 21 | 14.9 | 17 (81.0) | 1.82 (0.32-10.34) | 0.499 |
| Rest and painkiller | 72 | 33.5 | 52 (72.2) | 1.56 (0.59-4.13) | 0.371 | 28 | 19.9 | 24 (85.7) | 2.57 (0.46-14.32) | 0.281 |
| Additional symptom during headache | ||||||||||
| No (R) | 116 | 54.0 | 63 (54.3) | 1 | 88 | 62.4 | 57 (64.8) | 1 | ||
| Yes | 99 | 46.0 | 81 (81.8) | 3.79 (2.02-7.09) | <0.001** | 53 | 37.6 | 40 (75.5) | 1.67 (0.78-3.59) | 0.186 |
*Statistically significant at p<0.05
**Statistically significant at p<0.01
Participants who used painkillers had 2–3 times more chances for poor QoL compared to those who did not, both in headache patients with COVID-19 and non-COVID-19 (OR: 3.25; 95%CI: 1.75–6.05 with p<0.001 and OR: 2.34; 95% CI: 1.09–5.00 with p=0.029, respectively). Headache duration between 1–6 hours was associated with an increased risk of having poor QoL compared to participants who experienced the headache for less than one hour in both COVID-19 and non-COVID-19 groups (OR: 3.35; 95%CI: 1.64–6.83 and OR: 3.56; 95%CI: 1.42–8.94, respectively). In COVID-19 patients, a headache that got worse with activities was associated with poor QoL compared to the absence of a worsening factor (OR: 1.98; 95% CI: 1.01–3.90), and a combination of activity and noise as worsening factors was associated with an increase of nearly eight times the odds of poor QoL compared to the absence of a worsening factor (OR: 8.38; 95%CI: 1.78–39.56, with p=0.007). Meanwhile, in non-COVID-19 patients, bright light and a combination of activity/tired, bright light and noise increased the odds of poor QoL compared to the absence of worsening factors (OR: 6.00 and OR: 10.91, respectively).
In the COVID-19 group, having headache two times or more per week was associated with poor QoL when compared to participants who only had a headache once or twice per month (OR: 4.24; 95%CI: 2.13–8.41). Patients with additional symptoms accompanying headache were nearly four times more likely to have poor QoL (OR: 3.79, 95%CI: 2.02–7.09). In non-COVID-19 patients, neither of these two characteristics were associated with poor QoL.
Discussion
This study was conducted to examine the characteristics of headache between COVID-19 and non-COVID-19 patients and to compare the QoL between these groups. The results suggested that the characteristics of headache between COVID-19 and non-COVID-19 patients were slightly different in terms of location, pain sensation, pain intensity, and frequency. Although most participants complained of pain all over the head (bilateral), COVID-19 patients also reported that the pain was usually concentrated in one particular area or point, whereas non-COVID-19 patients reported pain usually only on one side of the head (left or right), thus resembling a migraine.
Non-COVID-19 headache patients experienced a pain with pressing followed by pulsating and fiery sensation (36.2%, 31.2%, and 20.6% respectively). Meanwhile, 61.4% of the COVID-19 patients complained of a pulsating headache and 20.9% had a pressing headache. Those with COVID-19 reported more pain intensity (moderate to severe) than non-COVID-19 (mild to moderate) while also reporting the use of medication. Similar results were reported by other studies. For instance, pulsating, or pressing sensation, high risk of drug resistance and recurrence appear to be more common in COVID-19 patients [23-25]. Frontal pain, pulsating type, higher pain intensity, and presence of nausea in COVID-19 patients were associated with lymphopenia, low C-reactive protein, and procalcitonin levels [26]. Viral infections other than COVID-19 - such as dengue - have shown headache sensation of throbbing (59.2%) or pressing (40.7%) patterns more frequently [27].
There are some mechanisms underlying the worsening headache in COVID-19 patients. First, the profound pain of headache is induced by vasodilatation, plasma protein release, and mast cell degranulation in cranial tissues and meninges [28-30]. Second, the receptors of angiotensin-converting enzyme 2 (ACE2) on endothelial vessels make blood arteries prone to SARS-CoV-2 invasion. ACE2 has been linked to various defensive mechanisms in the body, including antinociception and vasodilation. ACE2 also reduces excessive free radical generation, which helps to minimize oxidative stress [31]. In addition, the virus that occupies the receptors may disrupt the vascular homeostasis. The perivascular trigeminal nerve may be damaged as a result, leading in COVID-19 headache [32]. Third, SARS-CoV-2 may infiltrate the trigeminal nerve by indirect pathways as well. Mechanisms such as cytokine storm and vasculopathy are also postulated to explain trigeminal nerve activation during SARS-CoV-2 infection [33-35]. Fourth, another theory explains that COVID-19 headache is induced by SARS-CoV-2 that disturb gas exchange in alveoli. Consequently, COVID-19 patients may have lower blood oxygen levels that triggers ischemia [33, 36].
COVID-19 patients have a higher frequency of headaches than non-COVID-19 patients. They complained of headaches twice a week, sometimes almost every day, while non-COVID-19 patients, who only get sick once or twice a month on average. Headache may impact individual's life both during and between headache attacks, which later affect QoL. Several studies identified headaches as the most distressing symptom, particularly in COVID-19 patients, because they interfere with daily activities [7, 25, 37]. The majority of participants (67.7%) in this study had a poor QoL in terms of pain, social functioning, fatigue, and mental health. Indeed, patients with chronic daily headaches experience emotional disturbances significantly more [38]. Thus, reduced QoL among headache patients poses a major concern because of its widespread prevalence and its debilitating nature [39]. The economic impact that occurs is due to a decrease in work productivity, increased absenteeism and disruption in social and family relations [39].
Poor QoL in COVID-19 patients with headaches were associated with unemployment, non-health-related jobs, use of pain medication, headache duration, frequency of attacks, activities, conditions that aggravate pain, and additional symptoms. In non-COVID-19 individuals, data suggested that poor QoL was associated with pain medication use, headache duration, and factors that aggravated headache pain.
Headaches affect an individual's daily life and QoL negatively. The frequency, severity and other symptoms (such as nausea, phonophobia and photophobia, and also mood disorders) contribute to this negative outcome [40]. A recent study found that post-COVID-19 sequelae increased anxiety and hampered daily activities, such as full-time work and self-care, while also decreasing ones’ participation in social activities due to cognitive dysfunction [41].
There are several limitations in this study. For example, the investigation did not assess the types of headaches before COVID-19, which could have contributed to the characteristics of COVID-19 headache. The COVID-19 headache characteristics were not specified for its migraine or tension-type headache-like symptoms. Consequently, it might be indistinguishable from the primary headache disorders, especially on asymptomatic COVID-19 patients. Also, reports on headache characteristics were based on personal complaint that could not be determined accurately. Further studies regarding the processes by which SARS-CoV-2 assaults the CNS and causes headache are vital for improving our understanding of COVID-19 headache pathophysiology, which determines potential therapeutic strategies.
Conclusions
There are four key differences between COVID-19 and non-COVID-19 headache: location, pain sensation, pain intensity, and frequency. The COVID-19 headache found in this study was bilateral, pain centered in one specific area, with pulsating or pressing sensation; it was also of moderate to severe pain and occurred more than twice a week or every day. Meanwhile, the non-COVID-19 headache was bilateral, the pain centered on one side of the head with pressing or pulsating sensation, with reports of mild to moderate pain, and occurred once or twice a month. These comparisons are critical since headache has a negative impact on patients’ QoL. More in-depth research, particularly on the mechanisms of headache in both COVID-19 and non-COVID-19 patients, is still required to gain a better knowledge for headache management.
Acknowledgments
Authors would like to thank the staff at Department of Neurology of Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia for the assistance during the study.
Ethics approval
The study protocol was approved by the Ethical Committee of Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia (10/EA/FK-RSUDZA/2022).
Conflict of interest
All the authors declare that there are no conflicts of interest.
Funding
This study received no external funding.
Underlying data
All data underlying the results are available from the corresponding author upon reasonable request.
How to cite
Mutiawati E, Kusuma HI, Fathima R, et al. A comparison study of headache characteristics and headache-associated quality-of-life of COVID-19 and non-COVID-19 patients. Narra J 2022; 2 (3): e93 - http://doi.org/10.52225/narra.v2i3.93.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data underlying the results are available from the corresponding author upon reasonable request.