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Proposed pathway of headache pathophysiology. Nociceptive information coming from peripheral networks is transmitted to trigeminal ganglion acting as central hub between peripheral and central nervous systems. Next, this information is sent to TCC located in the brainstem, transmitted to diencephalon structures and terminated in various areas in cortex. The transmission in this pathway is linked to the pivotal involvement of neurotransmitters (e.g. glutamate, GABA and serotonin) and nociceptive neuropeptides (e.g. CGRP, substance P and PACAP) released from nerve fibers synapses, particularly nociceptive C-fibers and Aδ-fibers. The receptors of these signaling molecules are identified in both peripheral blood vessel, trigeminal ganglion and central structures, such as in cerebrospinal fluid and TCC 142,147 .
Source publication
Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19.
Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of Se...
Contexts in source publication
Context 1
... transmissions are then projected to the diencephalon structures, including the thalamus and hypothalamus, via the second-order neurons 143,146 . The third-order neurons are subsequently responsible for transmitting the information from diencephalic systems to various cortical areas associated with motoric, somatosensory, auditory, retrosplenial and visual functions 141,143 , leading to the manifestation of headache pain and other related symptoms (Figure 3). During these transmission processes, the release of neuropeptides, especially CGRP, is limited only in the meninges and in the central terminals of trigeminal afferents 147 . ...
Context 2
... transmissions are then projected to the diencephalon structures, including the thalamus and hypothalamus, via the second-order neurons 143,146 . The third-order neurons are subsequently responsible for transmitting the information from diencephalic systems to various cortical areas associated with motoric, somatosensory, auditory, retrosplenial and visual functions 141,143 , leading to the manifestation of headache pain and other related symptoms (Figure 3). During these transmission processes, the release of neuropeptides, especially CGRP, is limited only in the meninges and in the central terminals of trigeminal afferents 147 . ...
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... From a prognostic perspective, some studies have showed intriguing patterns, for instance, individuals enduring headaches reported shorter durations of infection, with negligible impact on mortality or hospital stay lengths compared to those without headaches 3,30 . Meta-analyses further shed light on the potential of headaches serving as markers of inpatient survival, yet a direct 10/14 correlation between headaches and the worsening prognosis or severity of infection remained elusive 43,44 . The influence of pre-existing headache history on the manifestation of headaches during and post-SARS-CoV-2 infections draws attention to the nuanced impact of prior headache conditions. ...
BACKGROUND AND OBJECTIVES
Addressing secondary headaches in SARS-CoV-2 infection is crucial for effective management and care optimization. This review aims to synthesize data on headache characteristics and the impact of pre-existing headache conditions on these symptoms in SARS-CoV-2 infection.
CONTENTS
A systematic search was conducted across multiple databases, including PubMed/Medline, Cochrane Collaboration, Web of Science, Scopus, LILACS, Embase, Open Grey, and Google Scholar, to identify studies on headache characteristics associated with SARS-CoV-2. The search focused on headache symptoms, characteristics, onset, duration, and response to treatment during and post-infection. Twenty-three studies met the inclusion criteria. Approximately 42.1% of individuals with SARS-CoV-2 reported headaches, resembling tension-type headaches and migraines. These headaches often manifested within the first three days of infection and could persist for up to four months. The data suggest that trigeminovascular activation and pro-inflammatory mediators play a significant role in headache pathogenesis, with pre-existing headache conditions exacerbating the symptoms. The importance of effective pain management strategies must be emphasized.
CONCLUSION
Headache is a prevalent symptom among SARS-CoV-2 infected individuals, with significant implications for patient care. The findings emphasize the importance of recognizing headache characteristics in SARS-CoV-2 management and suggest that tailored clinical approaches are essential for effective symptom relief.
Keywords:
COVID-19; Headache; Pain; Pandemic; SARS-CoV-2
... According to the data published by World Health Organization (WHO) in 2019, the ARTI, especially those of the lower respiratory tract infections (LRTI), were one of the leading causes for morbidity and mortality, which have been one of the public health problems worldwide [1]. Respiratory pathogens could get explosive during a short period of time due to their high contagion and rapid transmission [2,3]. More than two hundred viruses have been determined as the causative agents for ARTI with varying severity [4], such as respiratory syncytial virus (RSV), metapneumovirus (MPV), and rhinovirus (RVs). ...
Acute respiratory tract infections (ARTI) are caused by respiratory pathogens and range from asymptomatic infections to severe respiratory diseases. These diseases can be life threatening with high morbidity and mortality worldwide. Under the pandemic of coronavirus disease 2019 (COVID-19), little has been reported about the pathogen etiologies and epidemiology of patients suffering from ARTI of all age in Xiamen. Region-specific surveillance in individuals with ARTI of all ages was performed in Xiamen from January 2020 to October 2022. Here, we observed the epidemiological characteristics of thirteen pathogens within ARTI patients and further revealed the difference of that between upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In total 56.36 % (2358/4184) of the ARTI patients were positive for at least one respiratory pathogen. Rhinovirus (RVs, 29.22 %), influenza A (FluA, 19.59 %), respiratory syncytial virus (RSV, 18.36 %), metapneumovirus (MPV, 13.91 %), and adenovirus (ADV, 10.31 %) were the five leading respiratory pathogens. Respiratory pathogens displayed age- and season-specific patterns, even between URTI and LRTI. Compared with other groups, a higher proportion of FluA (52.17 % and 68.75 %, respectively) infection was found in the adult group and the elder group, while the lower proportion of RVs (14.11 % and 11.11 %) infection was also observed in them. Although ARTI cases circulated throughout the year, RVs, FluB, and BoV peaked in autumn, and FluA circulated more in summer. Besides, the co-infectious rate was 8.7 % with the most common for RVs. Logistic regression analyses revealed the correlations between respiratory pathogens and disease types. These results are essential for replenishing epidemiological characteristics of common respiratory pathogens that caused ARTI in Xiamen during the epidemic of COVID-19, and a better understanding of it might optimize the local prevention and clinical control.
... In general, the occurrence rates of COVID-19-induced headache range from 13.1% to 40% in China [5 , 14] , 55.1% in Egypt [15] , and 70.3% in Europe [16] . The global prevalence of headaches in a systematic review is more than 25% out of 104,751 COVID-19 cases [17] . Multiple variations need to be considered while comparing these data from different studies. ...
Headache is a common neurological symptom of Coronavirus disease 2019 (COVID-19) patients. However, the prevalence, comorbidities, and ethnic susceptibilities of COVID-19-induced headaches are not well-defined. We performed a retrospective chart review of patients who tested positive for SARS-CoV2 by reverse transcriptase-polymerase chain reaction (RT-PCR) in March and April 2020 at Massachusetts General Hospital, Boston, Massachusetts, USA. In the study, we identified 450 patients, 202 (44.9%) male, and 248 (55.1%) female, who tested positive for COVID-19. Headache is a significant painful symptom affecting 26% of patients. Female predominance is determined in sore throat, nasal congestion, hypogeusia, headache, and ear pain. In contrast, pneumonia and inpatient hospitalization were more prevalent in males. Younger patients (< 50) were more likely to develop sore throat, fatigue, anosmia, hypogeusia, ear pain, myalgia /arthralgia, and headache. In contrast, older (> 50) patients were prone to develop pneumonia and required hospitalization. Ethnic subgroup analysis suggests Hispanic patients were prone to headaches, nausea/vomiting, nasal congestion, fever, fatigue, anosmia, and myalgia/arthralgia compared to non-Hispanics. Headache risk factors include nausea/vomiting, sore throat, nasal congestion, fever, cough, fatigue, anosmia, hypogeusia, dizziness, ear pain, eye pain, and myalgia/arthralgia. Our study demonstrates regional gender, age, and ethnic variabilities in COVID symptomatology in Boston and the vicinity. It identifies mild viral, painful, and neurological symptoms are positive predictors of headache development in COVID-19.
... Since the first case of new coronavirus pneumonia was discovered at the end of 2019, this new coronavirus has spread to 211 countries and regions. The World Health Organization (WHO) believes that a global pandemic is underway, and the world is facing a large-scale virus crisis [23,31,36,42,49]. The wearing and production of medical masks, as a low-cost and effective means of protection, are encouraged by governments. ...
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... 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]. ...
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.
... In occupational cohorts, over 40% of workers suffer from headaches, and one in five have a headache that significantly affects their working capacity [65]. In fact, in most workers, headache disorders are much more prevalent than migraine [66]. Furthermore, patients with metabolic syndrome have headaches other than migraines, with a headache subtype distribution similar to that of the general population [67]. ...
A case–control study including 446 workers reporting headaches (cases; 136 males and 310 females, mean age 46.71 ± 10.84 years) and 446 age- and sex-matched colleagues without headaches (controls; mean age 45.44 ± 10.13) was conducted in the second half of 2020 in a sample drawn from socio health and commercial services companies to investigate the association of headache with lifestyle, metabolic, and work-related factors. Workers suffering from headache reported higher body weight (OR: 1.92, 95% CI: 1.46–2.53, p < 0.001), higher blood cholesterol (OR: 2.01, 95% CI: 1.46–2.77, p < 0.001), triglyceride (OR: 2.01, 95% CI: 1.20–3.35, p < 0.01), blood glucose (OR: 1.91, 95% CI: 1.16–3.24, p < 0.01), and blood pressure levels (OR: 1.76, 95% CI: 1.23–2.52, p < 0.01). In the year preceding the survey, cases had experienced a higher frequency of workplace violence (OR: 2.29, 95% CI: 1.25–4.20, p < 0.01 for physical aggression, OR: 2.22, 95% CI: 1.45–3.41, p < 0.001 for threat, OR: 2.74, 95% CI: 1.72–4.38, p < 0.001 for harassment) and were more frequently distressed (effort/reward ratio > 1) (OR: 1.82, 95% CI: 1.39–2.40, p < 0.001) than the controls. Compared to the controls, cases also had higher scores on anxiety and depression scales, lower scores on happiness, and lower levels of sleep quality (p < 0.001). The association of headaches with metabolic and mental health problems suggests that monitoring headaches in the workplace could help to identify workers at risk of impairment.
... 2 A systemic review and meta-analysis found that the prevalence of headaches was 2-fold higher among patients with COVID-19 than that of non-COVID individuals. 22 Furthermore, a previous study suggested that clinical features such as headaches found in acute illness could significantly predict the same feature as a long-term post-COVID sequel. 14 Therefore, the high prevalence of headaches as a clinical Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. ...
... 25,26 In addition, pandemic-induced multidimensional uncertainties are also responsible for many mental health and neurological disorders such as headaches. 7,8,22 Therefore, the cumulative impact of COVID-19 on headaches might be unprecedentedly diversified. ...
... Previous studies measured the overall prevalence of headaches among the general population and mainly hospital-discharged postacute COVID-19 survivors during the pandemic. 22,25,29 However, a significant portion of the patients with COVID-19 experienced mild symptoms and did not require hospital admission. The data regarding the association between SARS-CoV-2 infection and headache among general community dwellers are scarce. ...
Introduction:
Headache is one of the significant global public health concerns. Furthermore, it is a standard feature of patients with acute and postacute COVID-19.
Objectives:
This study aimed to estimate and compare the prevalence of headaches among postacute COVID and non-COVID individuals and identify and contrast the risk factors between both groups.
Methods:
This was a multicenter case-control study. Individuals who had recovered from acute SARS-CoV-2 infection were considered "case", and those who never tested positive for COVID-19 were considered "control." Headaches were measured using the musculoskeletal subscale of the subjective health complaints scale. Multiple logistic regression analysis was used to identify the predictors of headaches.
Results:
A total of 878 individuals (439 cases) aged 38.30 ± 12.77 years (mean ± standard deviation) participated in this study. The prevalence of headaches was 26.2% among COVID-19 survivors; however, only 10.7% of unaffected participants reported headaches at the same time. Regression analyses suggested that the recovery duration from acute COVID-19 ≤ 90 days (adjusted odds ratio [AOR] = 2.03, CI = 1.13-3.65) was the only predictor of headache among postacute COVID-19 survivors. However, the female gender (AOR = 3.09, 95% CI = 1.51-6.32), members of a joint family (AOR = 1.99, 95% CI = 1.02-3.90), and city dwellers (AOR = 2.43, 95% CI = 0.94-6.25) were the predictor of headache among non-COVID participants.
Conclusion:
This study found a higher prevalence of headaches among COVID-19 survivors. In addition, predictors of headache among cases and controls were unmatched, indicating heterogenous impact of COVID-19 on human health. The health care providers should be informed of the study's results when discussing better practices to mitigate the burden of headaches.
... In the central process, SARS-CoV-2 was detected in the brain tissue and cerebrospinal fluid due to the presence of angiotensin-converting enzyme 2 (ACE-2) receptors on the neurons and microglia in the dorsal horn. 17 An imbalance between ACE-2 and angiotensin II in the spinal cord is considered another factor associated with pain regulated through the central pathway. In the peripheral process, the virus is thought to enter the muscles and joints, resulting in an inflammatory response. ...
Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, may result in musculoskeletal tissue injury and is assumingly regulated through central and peripheral pathways. Muscle-specific creatinine kinase (CK-MM) is a specific biomarker used to indicate the presence of musculoskeletal tissue damage. This study aimed to investigate the correlation between the levels of CK-MM and the incidence of persistent myalgia in patients with post-COVID-19 syndromes. Methods: A cross-sectional study was conducted among COVID-19 survivors at the Faculty of Medicine and Clinical Pathology Laboratory, Universitas Airlangga, Surabaya from June - August 2022. The degree of pain of the myalgia was assessed using a visual analog scale (VAS), while CK-MM level was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). Pearson correlation test at α=0.05 was used to identify the correlation between the levels of CK-MM and the incidence of persistent myalgia in patients with post-COVID-19 syndromes. Results: A total of 84 participants were enrolled in the study and half (50%) of them reported persistent myalgia post-COVID-19 recovery. Fatigue was the patients' most common persistent symptom (63%). Of the total 42 patients with persistent myalgia, more than half (56%) had mild pain intensity (VAS score: 1–3), and almost all of them (41 patients) experienced myalgia during the COVID-19 diagnosis. All the patients with post-COVID-19 myalgia had normal levels of CK-MM (mean: 32.7 ng/mL; range: 12–93 ng/mL), suggesting no musculoskeletal tissue damage. Anova test suggested no significant different of CK-MM levels between those with and without myalgia in patients with post-COVID-19 syndromes p=0.054). Conclusion: There was no significant association between CK-MM levels and the incidence of persistent myalgia in patients with post-COVID-19 syndromes.
... The global prevalence of headaches in a systematic review of previous studies was more than 25% of 104,751 cases of COVID-19 (10) . SARS-direct CoV-2's invasion of trigeminal nerve terminals in the nasal cavity is the first plausible mechanism for COVID-19-associated headaches. ...
COVID-19 is a respiratory disease that spreads rapidly starting at the end of 2019. The resulting manifestations vary from respiratory symptoms to neurological symptoms. The variety of neurological symptoms found when coming to the Emergency Department triggered a study to examine the neurological features of COVID-19 patients. A retrospective descriptive examination of 2,659 patients hospitalized to the emergency department between March 1, 2020, and March 31, 2022, constitutes the basis of our study. There were patients of every age and gender represented. The study considered all clinical factors, such as comorbidities, clinical presentation, and neurologic manifestations such as cephalgia, vertigo, stroke, hypoxic encephalopathy, a disorder of consciousness, seizure, myalgia, ageusia/dysgeusia, and anosmia. The study results showed 2,659 confirmed COVID-19 patients at the Husada Utama Hospital and 1,484 COVID-19 patients with neurological manifestations, or 55.8%, were found. The most common neurological manifestations are cephalgia, and the least are seizures.
... Headache is one of the main neurological symptoms of SARS-CoV-2 infection, and is almost two times more prevalent in COVID-19 patients than other respiratory viral infections [38]. A previous study showed that the global prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases) [39]. Headache was the first reported symptom of COVID-19 in 42.2% (84/199), with prolonged headache persisting in 13.6% (27/199), and of those, more than 10.2% (20/199) lasted for more than 3 months [38]. ...
Little is known on the characteristics of headaches associated with coronavirus disease 2019 (COVID-19) in Indonesia. The objective of this study was to describe the characteristics of headache in post-COVID-19 patients, and its impact on the patients’ quality of life (QoL), as well as to determine the associated determinants of the poor QoL. A cross-sectional study was conducted in Banda Aceh, Indonesia. The demographic characteristics, clinical symptoms of COVID-19, characteristics of headache, and the QoL were collected and assessed. Headache was diagnosed and characterized using the International Classification of Headache Disorders, version 3 (ICHD-3). QoL was assessed using a Short Form 36 Health Survey (SF-36) tool. A logistic regression model was used to investigate the associated determinants of poor QoL in post-COVID-19 patients. A total of 215 post-COVID-19 patients were included in the final analysis, and 21.4% (46/215) of them had a poor QoL due to headache following COVID-19. Those who were unemployed and who contracted COVID-19 less than three months prior to the study had higher odds of having poor QoL compared to those who were employed and who contracted COVID-19 more than three months prior to the study. Low QoL was also related to headache that occurred less than one month after recovering from COVID-19 (compared to that which occurred longer than one month after); had a high frequency; had a combination sensation of pulsating, pressing, fiery, and stabbing pain; had a high severity score; and had additional symptoms accompanying the headache. In conclusion, headache related to COVID-19 is associated with low QoL among post-COVID-19 patients. A guideline on prevention measures of headache on COVID-19 patients, therefore, needs to be established to avoid long-term consequences.
