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Concomitant symptoms of persistent headache after COVID-19 of 421 participants in Latin America. Data are plotted as percentage. ap < 0.05; bp < 0.01; cp < 0.001 (p values by Pearson’s chi-square test). SF/F: sweating of the face or forehead; DUE/PC: drooping of the upper eyelid and/or pupillary constriction
Source publication
Background
Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache synd...
Citations
... Our study showed no statistically significant difference between the studied groups regarding age and gender. In contrast, previous studies showed that post-COVID headaches were commonly reported among females [3,16,17]. A potential explanation might be related to our small sample size which might have limited the statistical power and prevented the differences from being statistically significant. ...
(1) Background: Persistent post-COVID-19 headaches are emerging as a significant post-infection symptom. This study investigates the clinical characteristics of persistent post-COVID-19 headaches and the potential role of pro-inflammatory cytokines. (2) Methods: We conducted a pilot case–control study involving 84 participants divided into three groups: post-COVID with headache (n = 28), post-COVID without headache (n = 28), and healthy controls (n = 28). The detailed headache characteristics, including pain intensity, were assessed using the Visual Analog Scale (VAS). The serum levels of inflammatory cytokines (IL-6 and TNF-α) were measured. (3) Results: Post-COVID headaches predominantly presented as bilateral (53.6%) and throbbing (60.7%) in nature, with a median of 12 headache days per month and high pain intensity (median VAS score = 80). The associated symptoms were phonophobia (85.7%), fatigue (78.6%), and photophobia (75%). The serum levels of IL-6 and TNF-α were significantly higher in post-COVID headache patients than in the post-COVID without headache and healthy control groups (p < 0.001). A Receiver Operating Characteristic analysis showed that the circulating levels of IL-6 and TNF-α could discriminate our study groups at cutoffs with variable sensitivity and specificity. (4) Conclusions: Persistent post-COVID-19 headaches have diverse clinical characteristics and are associated with elevated circulating levels of pro-inflammatory cytokines, suggesting a potential underlying neuroinflammation.
... With 8-15% of COVID-19 patients presenting with persistent headaches during the first 6 months after infection. 37 They can be described as moderate to severe and persistent. 38 It is important to note that headaches can be the result of either systemic infection or even the neuroinvasive mechanisms of the disease. ...
... Neurological complaints that patients can have include cognitive disorders/fatigue, headaches, hyposmia/hypogeusia, and myalgia/ muscle weakness. 11,37 However, more serious complications can include stroke, seizure, ataxia, loss of gray matter, and neurodegenerative diseases. 10,14,15 Regardless, of many patients suffering from these manifestations there is still much research to do on this topic, especially in formulating a specific, personalized, and tailored treatment for these patients. ...
COVID-19, a highly infectious disease, caused a worldwide pandemic in early 2020. According to the World Health Organization (WHO), COVID-19 has resulted in approximately 774 million cases and around 7 million deaths. The effects of COVID-19 are well known; however, there is a lack of information on the pathophysiological mechanisms underlying the symptoms that comprise Post-Acute COVID-19 Syndrome (PACS) or Long COVID-19. Neurological sequelae are common, with cognitive dysfunction being one of the foremost symptoms. Research indicates that elevated inflammatory levels and increased oxidative stress may play a role in the etiology and severity of PACS. Treatment options are extremely limited, and there is no consensus among the medical and scientific communities on how to manage the disease. Nevertheless, many scientists advocate for using antioxidants for symptomatic therapy and cognitive behavior therapy for supportive care. Additionally, current research aims to ameliorate several aspects of the inflammatory cascade. This review highlights the intracellular and extracellular pathways crucial to the neurological manifestations of PACS, providing valuable information for healthcare professionals and scientists. Given the complex nature of PACS, understanding these pathways is essential for developing new treatment options. Assessing PACS is challenging, and reviewing current therapeutic options while proposing a triad of potential therapeutic elements will add value to clinical assays and guidelines. Current therapeutic strategies, such as antioxidants/vitamin supplements, neurogenic stem cell therapy, and mitochondrial therapy, could be combined to enhance their effectiveness. Future research should focus on validating these approaches and exploring new avenues for the effective treatment of PACS.
... The long-term association between anosmia/ageusia and headache was not evaluated either. In addition, it remains unclear whether post-COVID-19 headache is a subtype of a new daily persistent headache or a chronic form of a disorder that in most patients is restricted to the acute phase [42,43]. ...
To describe the need and effectiveness of acute and preventive medications in a series of 100 consecutive patients referred due to COVID-19-related headaches. Patients were aged 48.0 (standard deviation (SD): 12.4), 84% were female, and 56% had a prior history of headache. The most common headache phenotype was holocranial (63%), frontal (48%), pressing (75%), of moderate intensity (7 out of 10), and accompanied by photophobia (58%). Acute medication was required by 93%, with paracetamol (46%) being the most frequently used drug, followed by ibuprofen (44%). The drugs with the highest proportion of a 2 h pain-freedom response were dexketoprofen (58.8%), triptans (57.7%), and ibuprofen (54.3%). Preventive treatment was required by 75% of patients. The most frequently used drugs were amitriptyline (66%), anesthetic blockades (18%), and onabotulinumtoxinA (11%). The drugs with the highest 50% responder rate were amitriptyline (45.5%), mirtazapine (50%), and anesthetic blockades (38.9%). The highest 75% responder rate was experienced following onabotulinumtoxinA (18.2%). In conclusion, most patients required acute medication, with triptans and non-steroidal anti-inflammatory drugs achieving the best responses. Three-quarters of patients required preventive medication. The most frequently used drug was amitriptyline, which obtained the best results. In some treatment-resistant patients, anesthetic blockades and onabotulinumtoxinA were also beneficial.
... Now our stratification shows that as many as 6.5% had no headache diagnosis and 9.8% reported an unchanged pre-existing headache. The finding that 25% of patients present with new onset of daily headache in association with post-COVID-19 syndrome is consistent with recently published data [30]. Furthermore, the four headache groups also differed significantly in the Functional Assessment Scale (FAS); Patient Health Questionnaire-9 (PHQ-9) and Post-COVID Fatigue Scale (PCFS). ...
Background
New onset or worsening of a headache disorder substantially contributes to the disease burden of post-COVID-19. Its management poses a suitable means to enhance patients’ participation in professional, social, and personal activities. Unfortunately, the pathophysiology of post-COVID-19 headaches is poorly understood. This study aims to investigate the role of (neuro-) inflammatory mechanisms in order to guide the development of anti-inflammatory treatment strategies.
Methods
We included patients from the interdisciplinary post-COVID-19 Rehabilitation Study (PoCoRe, n = 184 patients) run at a tertiary care university hospital, comprising patients with PCR-confirmed SARS-CoV-2 infection ≥ 6 weeks prior to their initial consultation. Patients reporting any headache since their infection were considered for this study (n = 93). These were interviewed and classified according to the International Classification of Headache Disorders, Third Edition (ICHD-3) by headache specialists. Patient sera were additionally analysed for levels of VILIP-1, MCP-1 (CCL2), sTREM-2, BDNF, TGF-ß1, VEGF, IL-6, sTREM-1, ß-NGF, IL-18, TNF-alpha, sRAGE, and CX3CL1 (Fractalkine). Markers of inflammation were compared between four groups of patients (none, unchanged, worsened, or new headache disorder).
Results
Patients reported experiencing more severe headaches (n = 17), new onset headaches (n = 46), unchanged headaches (n = 18), and surprisingly, some patients denied having any headaches (n = 12) despite self-reports. Serum levels of CX3CL1 were increased in the worsened (2145 [811–4866] pg/ml) and new onset (1668 [0-7357] pg/ml) headache group as compared to patients with no (1129 [0-5379] pg/ml) or unchanged (1478 [346–4332] pg/ml) headaches. Other markers also differed between groups, but most significantly between patients with worsened (TGF-ß1: 60 [0-310] pg/ml, VEGF: 328 [86–842] pg/ml, ß-NGF: 6 [3–38] pg/ml) as compared to unchanged headaches (TGF-ß1: 29 [0–77] pg/ml, VEGF: 183 [72–380] pg/ml, ß-NGF: 3 [2–89] pg/ml). The results did not differ between headache phenotypes.
Discussion
This study provides evidence that worsened or new headaches following COVID-19 are associated with pro-(neuro-)inflammatory profiles. This supports the use of anti-inflammatory treatment options in this population, especially in the subacute phase.
... For instance, a study focused on participants across 11 Latin American countries who had experienced NDPH following COVID-19 infection highlighted that the majority of these participants began experiencing persistent headaches within the first two weeks of their COVID-19 onset. Notably, characteristics such as the headache's occipital location, severe intensity, burning character, and radiating pain were more prevalent among those diagnosed with NDPH compared to those with non-NDPH headaches (Carrión et al., 2023). ...
Headache is a prevalent symptom of COVID-19 and long COVID, and it can be debilitating. If you experience headaches, it is essential to seek medical attention immediately to ensure proper diagnosis and treatment. It has been observed that a considerable proportion of individuals (ranging from 6-45%) diagnosed with COVID-19 and exhibiting symptoms of headache during the acute phase, tend to experience persistent headaches in the post-symptomatic phase. This observation highlights the need for further research into the long-term effects of COVID-19, particularly concerning its neurological impact on patients. It is imperative to conduct more studies to understand the underlying mechanisms and pathophysiology of such headaches in order to provide appropriate treatment and management strategies for those affected. The pathophysiology is not clear. Headaches during COVID-19 can stem from both direct effects of the virus and broader systemic reactions like inflammation and hypoxemia. Key symptoms such as headache, loss of smell, and loss of taste suggest the virus's potential to cause local inflammation early in the infection. Neurological findings, including microhemorrhages in the olfactory bulb, underline the virus's impact on the nervous system. Inflammatory markers are elevated in patients with severe headaches, indicating an inflammatory response. The trigeminovascular system's activation due to olfactory and nasal inflammation, alongside a hypoxic state from reduced oxygen levels, are believed to contribute to headaches. SARS-CoV-2's entry into the central nervous system (CNS), possibly through the olfactory pathway or a compromised BBB, can lead to a range of neurological symptoms, with inflammation and coagulopathy playing roles in headache development. Persistent headaches post-infection suggest a lasting inflammatory response, necessitating further research and clinical attention for management.
This analysis article aimed to identify and analyze all articles published on the post-COVID-19 condition in Latin America and the Caribbean, focusing on epidemiology, clinical characteristics, and risk of bias. We did a systematic survey of the literature with broad inclusion criteria. The only exclusion criteria were articles referring to post-acute COVID-19 sequelae after an intensive care unit stay, which we distinguish from the post-COVID-19 condition. We searched MEDLINE/PubMed, LILACS, SciELO, Scopus, Web of Science, and Epistemonikos. We included 55 records, of which 48 were original articles (44 were observational research, 29 of which had a comparison group; and four reviews). Various definitions for long COVID were reported, or none, and few used the World Health Organization criteria. None of the included studies reported prevalence rates for the region. We extracted the reported signs and symptoms of long COVID for our region. Using the Johanna Briggs Institute critical appraisal tools for observational analytic research, we found that most included studies were prone to limitations and biases. We conclude that more research should be done on the post-COVID-19 condition in Latin America and the Caribbean, using rigorous study designs to inform public health strategies.
ZUSAMMENFASSUNG
Die Kopfschmerzklassifikation der International Headache Society unterscheidet in ihrem Kapitel 4 verschiedene primäre Kopfschmerzerkrankungen, die als selten gelten und als eigenständige Entitäten aufgefasst werden. Zu diesen gehören der primäre Hustenkopfschmerz, der primäre Anstrengungskopfschmerz, der primäre Sexualkopfschmerz, der primäre Donnerschlagkopfschmerz, der Kältekopfschmerz, der Kopfschmerz durch Einwirkung von Druck oder Zug auf den Kopf, der primäre stechende Kopfschmerz, der Münzkopfschmerz, der schlafgebundene Kopfschmerz und der neu aufgetretene tägliche anhaltende Kopfschmerz. Es handelt sich bei den primären Formen um prinzipiell gutartige Erkrankungen, die aber die Lebensqualität der Betroffenen erheblich einschränken können. Auch müssen potenziell bedrohliche sekundäre Kopfschmerzerkrankungen mit ähnlichem oder identischem Phänotyp ausgeschlossen werden. Aufgrund einer Analyse der publizierten Fallberichte und Fallserien und eines Expertenkonsenses werden für diese Kopfschmerzerkrankungen Therapieempfehlungen gegeben, auch wenn große randomisierte, kontrollierte Therapiestudien nicht vorliegen.
