Headache as a COVID-19 onset symptom or Post-COVID symptom according to the SARS-CoV-2 Variant.

INTRODUCTION: COVID19 associated headaches are highly common and there is currently an unmet need to better understand their association with SARSCoV2 variants. Headaches are a prevalent symptom in the acute phase of COVID19 and are associated with a better prognosis and better immune response. They are also a relevant post-COVID symptom. AREAS COVERED: This article analyses the differences in the prevalence of headache as an onset symptom and in post-COVID headache among the different SARS-CoV-2 variants: the historical strain, Alpha, Delta and Omicron. The different pathophysiological mechanisms by which SARS-CoV-2 infection may cause headache are also discussed. EXPERT OPINION: The presence of headache at the acute phase is a risk factor for post-COVID headache, whereas a history of primary headache does not appear to be associated with post-COVID headache. The prevalence of headache as an onset symptom appears to be variable for the different SARS-CoV-2 variants, but current data are inconclusive. However, the current evidence also suggests that headache represents a prevalent symptom in the acute and post-infection COVID-19 phase, regardless of SARS-CoV-2 variant.

Neurological Sequelae of COVID-19.

BACKGROUND: Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE: In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS: A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS: A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.

Postacute/Long COVID in Pediatrics: Development of a Multidisciplinary Rehabilitation Clinic and Preliminary Case Series.

ABSTRACT: The long-term sequelae after SARS-CoV-2 infections in children is unknown. Guidance is needed on helpful models of care for an emerging subset of pediatric patients with postacute/long COVID who continue to experience persistent symptoms after initial COVID-19 diagnosis. Here, we describe a pediatric multidisciplinary post-COVID-19 rehabilitation clinic model as well as a case series of the initial cohort of patients who presented to this clinic. A consecutive sample of nine patients (pediatric patients <21 yrs of age) who presented to our clinic are included. The most common presenting symptoms were fatigue (8 of 9 patients), headaches (6 of 9), difficulty with schoolwork (6 of 8), "brain fog" (4 of 9), and dizziness/lightheadedness (4 of 9). Most patients had decreased scores on self-reported quality-of-life measures compared with healthy controls. In the patients who participated in neuropsychological testing, a subset demonstrated difficulties with sustained auditory attention and divided attention; however, most of these patients had preexisting attention and/or mood concerns. There were also some who self-reported elevated depression and anxiety symptoms. Pediatric patients with postacute/long COVID may present with a variety of physical, cognitive, and mood symptoms. We present a model of care to address these symptoms through a multidisciplinary rehabilitation approach.

[Clinical manifestations of COVID-19 in children]. / Nevrologicheskie proyavleniya COVID-19 u detei.

The neurological symptoms of COVID-19 in children (in Dyurtyuli area, Republic of Bashkortostan) are analyzed and brief review of the literature is undertaken in the paper. 137 children underwent swab test for COVID-19. The disease was diagnosed in 9 of them. Only respiratory symptoms were observed in 3 children, a combination of respiratory with anosmia or/and headache - in 3, asymptomatic form - in another 3. A case of a 7-years old girl suffering from COVID-19 with respiratory symptoms as well as anosmia and headache is presented. According to the review of the literature, COVID - 19 in children is usually milder than in adults, but in some cases may lead to neurological consequences. Multisystem inflammatory syndrome may lead to the development symptoms of encephalopathy (altered mental status, headache) and stroke. Autoimmune complications such as Gillian-Barre syndrome develop simultaneously or after resolving of the infectious process. The development of viral meningoencephalitis in COVID-19 is questionable.

Clinical features of COVID-19 in Ghana: symptomatology, illness severity and comorbid non-communicable diseases.

OBJECTIVE: This analysis described the clinical features of COVID-19 in the early phase of the pandemic in Ghana. METHODS: Data were extracted from two national COVID-19 treatment centers in Ghana for over 11 weeks(from March to May 2020). Descriptive and inferential statistics were performed. Modified Ordered Logistic and Negative Binomial Regression analysis were applied to establish factors associated with illness severity and Non-communicable Disease (NCDs) counts respectively. All analysis was conducted at the 95% confidence level (p-value ≤ 0.05) using Stata 16. RESULTS: Among the 275 patients, the average age was 40.7±16.4, with a preponderance of males (54.5%). The three commonest symptoms presented were cough (21.3%), headache (15.7%), and sore throat (11.7%). Only 7.6% of the patients had a history of fever. Most patients were asymptomatic (51.65). Approximately 38.9% have an underlying co-morbid NCDs, with Hypertension (32.1%), Diabetes (9.9%), and Asthma (5.2%) being the three commonest. The odds of Moderate/severe (MoS) was significantly higher for those with unknown exposures to similar illness [aOR(95%CI) = 4.27(1.12-10.2)] compared with non-exposure to similar illness. An increased unit of NCD's count significantly increased the odds of COVID-19 MoS illness by 26%[cOR(95%CI) =1.26(1.09-1.84)] and 67% (adjusting for age) [aOR(95%CI)=1.67(1.13-2.49)]. CONCLUSION: The presence of cardiovascular co-morbidities dictated the frequency of reported symptoms and severity of COVID-19 infection in this sample of Ghanaians. Physicians should be aware of the presence of co-morbid NCDs and prepare to manage effectively among COVID-19 patients. FUNDING: None declared.

Sociodemographic and clinical characteristics of the first cohort of COVID-19 recoveries at two national treatment centres in Accra, Ghana.

INTRODUCTION: COVID-19 is a new disease, knowledge on the mode of transmission and clinical features are still evolving, new tests are being developed with inherent challenges regarding interpretation of tests results. There is generally, a gap in knowledge on the virus globally as the pandemic evolves and in Ghana, there is dearth of information and documentation on the clinical characteristics of the virus. With these in mind, we set out to profile the initial cohort of COVID-19 patients who recovered in Ghana. METHODS: We reviewed clinical records of all confirmed cases of COVID-19 who had recovered from the two main treatment centres in Accra, Ghana. Descriptive data analysis was employed and presented in simple and relational tables. Independent t-test and ANOVA were used to determine differences in the mean age of the sexes and the number of days taken for the first and second retesting to be done per selected patient characteristics. RESULTS: Of the 146 records reviewed, 54% were male; mean age of patients was 41.9 ± 17.5 years, nearly half were asymptomatic, with 9% being severely ill. The commonest presenting symptoms were cough (22.6%), headache (13%) and sore throat (11%) while the commonest co-morbidities were hypertension (25.3%), diabetes mellitus (14%) and heart disease (3.4%). CONCLUSION: COVID-19 affected more males than females; nearly half of those infected were asymptomatic. Cough, headache and sore throat were the commonest symptoms and mean duration from case confirmation to full recovery was 19 days. Further research is required as pandemic evolves. FUNDING: None declared.

Prevalence of Symptoms More Than Seven Months After Diagnosis of Symptomatic COVID-19 in an Outpatient Setting.

BACKGROUND: With millions of SARS-CoV-2 infections worldwide, increasing numbers of patients are coming forward with long-term clinical effects of the disease lasting several weeks to months. OBJECTIVE: To characterize symptoms 7 to 9 months after diagnosis of COVID-19. DESIGN: Self-reported surveys and semistructured telephone interviews at enrollment and 30 to 45 days and 7 to 9 months from diagnosis. SETTING: From 18 March to 15 May 2020, symptomatic persons who tested positive for SARS-CoV-2 at the Geneva University Hospitals were followed by CoviCare, a virtual, clinical, outpatient follow-up program. Persons were contacted again at 30 to 45 days and 7 to 9 months from diagnosis. PARTICIPANTS: Persons who were a part of the CoviCare program from 18 March to 15 May 2020. MEASUREMENTS: A standardized interview of symptoms consistent with COVID-19, with grading of intensity. RESULTS: Of the 629 participants in the study who completed the baseline interviews, 410 completed follow-up at 7 to 9 months after COVID-19 diagnosis; 39.0% reported residual symptoms. Fatigue (20.7%) was the most common symptom reported, followed by loss of taste or smell (16.8%), dyspnea (11.7%), and headache (10.0%). LIMITATION: Limitations include generalizability and missing data for 34.8% of participants. CONCLUSION: Residual symptoms after SARS-CoV-2 infection are common among otherwise young and healthy persons followed in an outpatient setting. These findings contribute to the recognition of long-term effects in a disease mostly counted by its death toll to date by promoting communication on postacute sequelae of SARS-CoV-2 and encouraging physicians to continue long-term monitoring of their patients. PRIMARY FUNDING SOURCE: None.

Frequency and phenotype of headache in covid-19: a study of 2194 patients.

To estimate the frequency of headache in patients with confirmed COVID-19 and characterize the phenotype of headache attributed to COVID-19, comparing patients depending on the need of hospitalization and sex, an observational study was done. We systematically screened all eligible patients from a reference population of 261,431 between March 8 (first case) and April 11, 2020. A physician administered a survey assessing demographic and clinical data and the phenotype of the headache. During the study period, 2194 patients out of the population at risk were diagnosed with COVID-19. Headache was described by 514/2194 patients (23.4%, 95% CI 21.7-25.3%), including 383/1614 (23.7%) outpatients and 131/580 (22.6%) inpatients. The headache phenotype was studied in detail in 458 patients (mean age, 51 years; 72% female; prior history of headache, 49%). Headache was the most frequent first symptom of COVID-19. Median headache onset was within 24 h, median duration was 7 days and persisted after 1 month in 13% of patients. Pain was bilateral (80%), predominantly frontal (71%), with pressing quality (75%), of severe intensity. Systemic symptoms were present in 98% of patients. Headache frequency and phenotype was similar in patients with and without need for hospitalization and when comparing male and female patients, being more intense in females.Trial registration: This study was supported by the Institute of Health Carlos III (ISCIII), code 07.04.467804.74011 and Regional Health Administration, Gerencia Regional de Salud, Castilla y Leon (GRS: 2289/A/2020).

A Review of Neurological Involvement in Patients with SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative pathogen of the recent pandemic of coronavirus disease 19 (COVID-19). As the infection spreads, there is increasing evidence of neurological and psychiatric involvement in COVID-19. Headache, impaired consciousness, and olfactory and gustatory dysfunctions are common neurological manifestations described in the literature. Studies demonstrating more specific and more severe neurological involvement such as cerebrovascular insults, encephalitis and Guillain-Barre syndrome are also emerging. Respiratory failure, a significant condition that leads to mortality in COVID-19, is hypothesized to be partly due to brainstem impairment. Notably, some of these neurological complications seem to persist long after infection. This review aims to provide an update on what is currently known about neurological involvement in patients with COVID-19 due to SARS-CoV-2 infection. In this review, we demonstrate invasion routes of SARS-CoV-2, provide evidence to support the neurotropism hypothesis of the virus, and investigate the pathological mechanisms that underlie neurological complications associated with SARS-CoV-2.

'Long COVID': persistent COVID-19 symptoms in survivors managed in Lagos State, Nigeria.

BACKGROUND: Coronavirus disease once thought to be a respiratory infection is now recognised as a multi-system disease affecting the respiratory, cardiovascular, gastrointestinal, neurological, immune, and hematopoietic systems. An emerging body of evidence suggests the persistence of COVID-19 symptoms of varying patterns among some survivors. This study aimed to describe persistent symptoms in COVID-19 survivors and investigate possible risk factors for these persistent symptoms. METHODS: The study used a retrospective study design. The study population comprised of discharged COVID-19 patients. Demographic information, days since discharge, comorbidities, and persistent COVID-19 like symptoms were assessed in patients attending the COVID-19 outpatient clinic in Lagos State. Statistical analysis was done using STATA 15.0 software (StataCorp Texas) with significance placed at p-value < 0.05. RESULTS: A total of 274 patients were enrolled in the study. A majority were within the age group > 35 to ≤49 years (38.3%), and male (66.1%). More than one-third (40.9%) had persistent COVID-19 symptoms after discharge, and 19.7% had more than three persistent COVID-like symptoms. The most persistent COVID-like symptoms experienced were easy fatigability (12.8%), headaches (12.8%), and chest pain (9.8%). Symptomatic COVID-19 disease with moderate severity compared to mild severity was a predictor of persistent COVID-like symptoms after discharge (p < 0.05). CONCLUSION: Findings from this study suggests that patients who recovered from COVID-19 disease may still experience COVID-19 like symptoms, particularly fatigue and headaches. Therefore, careful monitoring should be in place after discharge to help mitigate the effects of these symptoms and improve the quality of life of COVID-19 survivors.

New-Onset Seizures in Three COVID-19 Patients: A Case Series.

SUMMARY: Neurological manifestations of coronavirus disease 2019 most commonly present in severe cases and range from mild complications, such as headache and dizziness, to severe complications, such as encephalopathy and acute cerebrovascular disease. Seizures, however, are an underreported neurological manifestation of this disease. We present three critically ill coronavirus disease 2019 patients with EEG monitoring who developed new-onset seizures and encephalopathy up to three-and-a-half weeks after symptom onset. There are several speculated etiologies for the development of new-onset seizures; however, the pathogenic mechanism remains unknown. Testing of coronavirus disease 2019 in the cerebrospinal fluid in addition to extensive research on neurological manifestations is warranted.

Diagnostic accuracy of symptoms as a diagnostic tool for SARS-CoV 2 infection: a cross-sectional study in a cohort of 2,173 patients.

BACKGROUND: The SARS-CoV-2 pandemic continues to be a priority health problem; According to the World Health Organization data from October 13, 2020, 37,704,153 confirmed COVID-19 cases have been reported, including 1,079,029 deaths, since the outbreak. The identification of potential symptoms has been reported to be a useful tool for clinical decision-making in emergency departments to avoid overload and improve the quality of care. The aim of this study was to evaluate the performances of symptoms as a diagnostic tool for SARS -CoV-2 infection. METHODS: An observational, cross-sectional, prospective and analytical study was carried out, during the period of time from April 14 to July 21, 2020. Data (demographic variables, medical history, respiratory and non-respiratory symptoms) were collected by emergency physicians. The diagnosis of COVID-19 was made using SARS-CoV-2 RT-PCR. The diagnostic accuracy of these characteristics for COVID-19 was evaluated by calculating the positive and negative likelihood ratios. A Mantel-Haenszel and multivariate logistic regression analysis was performed to assess the association of symptoms with COVID-19. RESULTS: A prevalence of 53.72% of SARS-CoV-2 infection was observed. The symptom with the highest sensitivity was cough 71%, and a specificity of 52.68%. The symptomatological scale, constructed from 6 symptoms, obtained a sensitivity of 83.45% and a specificity of 32.86%, taking ≥2 symptoms as a cut-off point. The symptoms with the greatest association with SARS-CoV-2 were: anosmia odds ratio (OR) 3.2 (95% CI; 2.52-4.17), fever OR 2.98 (95% CI; 2.47-3.58), dyspnea OR 2.9 (95% CI; 2.39-3.51]) and cough OR 2.73 (95% CI: 2.27-3.28). CONCLUSION: The combination of ≥2 symptoms / signs (fever, cough, anosmia, dyspnea and oxygen saturation < 93%, and headache) results in a highly sensitivity model for a quick and accurate diagnosis of COVID-19, and should be used in the absence of ancillary diagnostic studies. Symptomatology, alone and in combination, may be an appropriate strategy to use in the emergency department to guide the behaviors to respond to the disease. TRIAL REGISTRATION: Institutional registration R-2020-3601-145, Federal Commission for the Protection against Sanitary Risks 17 CI-09-015-034, National Bioethics Commission: 09 CEI-023-2017082 .

Clinical and epidemiological characteristics of children with SARS-CoV-2 infection: a case series in Sinaloa.

Background: The SARS-CoV-2 virus may affect both adults and children. Although COVID-19 has a lower prevalence in infancy and has been described as mild, the clinical characteristics may vary, and there is a possibility of complications. The objectives of this study were to describe the clinical and epidemiological aspects of confirmed COVID-19 pediatric cases in the state of Sinaloa, Mexico, during the first 3 months of the pandemic, and children admitted with COVID-19 to a secondary hospital. Methods: This case series includes all patients with SARS-CoV-2 infection confirmed by PCR (polymerase chain reaction) test, identified in the state epidemiological surveillance system (SISVER) between March 1 and May 31, 2020. Confirmed patients admitted to the Sinaloa Pediatric Hospital (HPS) in the same period are also described. Results: Fifty-one children with SARS-CoV-2 were included, of which ten were admitted to the HPS. The median age was 10 years. The more frequent symptoms were fever (78%), cough (67%), and headache (57%). Most cases were mild or asymptomatic. Three patients with comorbidities died. Only four of ten patients identified in HPS were admitted with the diagnosis of possible COVID-19. Conclusions: SARS-CoV-2 infection in children was mostly mild or asymptomatic, and the clinical presentation varied. There is a possibility of complications, especially in children with comorbidities.

Introducción: El SARS-CoV-2 puede afectar tanto a adultos como a niños. Aunque la COVID-19 presenta menor prevalencia en la infancia y se ha descrito como leve, las características clínicas pueden ser variables y existe la posibilidad de complicaciones. Los objetivos de este estudio fueron describir las características clínicas y epidemiológicas de los casos pediátricos confirmados en el Estado de Sinaloa, México, durante los primeros 3 meses de la pandemia, y de los niños con COVID-19 internados en un hospital de segundo nivel. Métodos: Esta serie de casos incluyó pacientes con infección por SARS-CoV-2 confirmados por prueba de reacción en cadena de la polimerasa (PCR), identificados en el Sistema de Vigilancia Epidemiológica de Enfermedades Respiratorias (SISVER) del 1 de marzo al 31 de mayo de 2020. Se describen también las características de todos los niños confirmados en el Hospital Pediátrico de Sinaloa (HPS) en las mismas fechas. Resultados: Se incluyeron 51 niños con infección por SARS-CoV-2, de los cuales 10 fueron internados en el HPS. La mediana de edad fue de 10 años. Los síntomas más frecuentes fueron fiebre (78%), tos (67%) y cefalea (57%). La mayoría de los casos fueron leves o asintomáticos. Tres pacientes con comorbilidad fallecieron. Solo cuatro de diez pacientes identificados en el HPS ingresaron bajo sospecha de COVID-19. Conclusiones: La infección por SARS-CoV-2 en los niños fue, en su mayoría, asintomática o leve, y la presentación fue variable. Existe la posibilidad de que se produzcan complicaciones, principalmente en niños con comorbilidad.

Symptômes associés au frottis SRAS-CoV-2-positif chez des enfants de l'Alberta.

CONTEXTE: La recherche sur les enfants atteints d'une infection à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) a principalement porté sur les enfants amenés aux services des urgences. Nous avons voulu identifier les symptômes plus souvent associés à un frottis SRAS-CoV-2-positif chez les enfants non hospitalisés. MÉTHODES: Nous avons procédé à une étude observationnelle chez des enfants soumis au dépistage et suivis pour une infection à SRAS-CoV-2 confirmée sur des prélèvements de sécrétions nasales, nasopharyngées, de la gorge et autres (p. ex., aspiration nasopharyngée, sécrétions trachéales ou non spécifiées) entre le 13 avril et le 30 septembre 2020 en Alberta. Nous avons calculé les rapports de vraisemblance (RV) positifs entre les symptômes autodéclarés et les frottis SRAS-CoV-2-positifs dans la cohorte entière et dans 3 analyses de sensibilité : tous les enfants présentant au moins 1 symptôme, tous les enfants, symptomatiques ou non, soumis au dépistage par suite d'une recherche de contacts, et tous les enfants de 5 ans et plus. RÉSULTATS: Nous avons analysé les résultats chez 2463 enfants soumis au dépistage de l'infection à SRAS-CoV-2; 1987 enfants se sont révélés positifs et 476 négatifs. Parmi les enfants SRAS-CoV-2-positifs, 714 (35,9 %) n'ont déclaré aucun symptôme. Même si la toux (24,5 %) et la rhinorrhée (19,3 %) étaient les 2 symptômes les plus fréquents chez les enfants ayant contracté le SRAS-CoV-2, elles étaient fréquentes également chez ceux dont les résultats étaient négatifs et ne permettaient pas de prédire un résultat positif (RV positif 0,96, intervalle de confiance [IC] à 95 % 0,81­1,14 et 0,87, IC à 95 % 0,72­1,06, respectivement). L'anosmie/agueusie (RV positif 7,33, IC à 95 % 3,03­17,76), les nausées et vomissements (RV positif 5,51, IC à 95 % 1,74­17,43), les céphalées (RV positif 2,49, IC à 95 % 1,74­3,57) et la fièvre (RV positif 1,68, IC à 95 % 1,34­2,11) ont été les symptômes les plus prédictifs d'un résultat SRAS-CoV-2-positif. Le RV positif pour la combinaison anosmie et agueusie, nausées et vomissements, et céphalées était de 65,92 (IC à 95 % 49,48­91,92). INTERPRÉTATION: Environ les deux tiers des enfants déclarés SRAS-CoV-2-positifs ont manifesté des symptômes, et les symptômes les plus étroitement associés à un frottis SRAS-CoV-2-positif étaient l'anosmie/agueusie, les nausées et les vomissements, les céphalées et la fièvre.

Immunotherapies and COVID-19 related Neurological manifestations: A Comprehensive Review Article.

In December 2019, an outbreak of pandemic severe respiratory distress syndrome coronavirus disease 2019 (COVID-19) initially occurred in China, has spread the world resulted in serious threats to human public health. Uncommon neurological manifestations with pathophysiological symptoms were observed in infected patients including headache, seizures, and neuroimmunological disorders. Regardless of whether these neurological symptoms are direct or indirect casual infection relationship, this novel viral infection has a relevant impact on the neuroimmune system that requires a neurologist's careful assessment. Recently, the use of immunotherapy has been emerged in fighting against COVID-19 infection despite the uncertain efficiency in managing COVID-19 related disorders or even its proven failure by increasing its severity. Herein, the author is addressing the first approaches in using immunotherapies in controlling COVID-19 viral impact on the brain by highlighting their role in decreasing or increasing infection risks among subjects. This point of view review article supports the use of immunotherapies in managing COVID-19 neurological disorders but in optimal timing and duration to ensure the maximum therapeutic outcome by reducing morbidity and mortality rate. Based on recently published data, the current review article highlights the beneficial effects and drawbacks of using immunotherapies to combat COVID-19 and its neurological symptoms.

Headache associated with COVID-19: Frequency, characteristics and association with anosmia and ageusia.

OBJECTIVES: To assess the frequency and characteristics of headache in patients with COVID-19 and whether there is an association between headache and anosmia and ageusia. METHODS: This was a cross-sectional study. Consecutive patients admitted to hospital with COVID-19, confirmed by reverse transcription polymerase chain reaction (RT-PCR) technique, were assessed by neurologists. RESULTS: Seventy-three patients were included in the study, 63% were male; the median age was 58 years (IQR: 47-66). Forty-seven patients (64.4%) reported headaches, which had most frequently begun on the first day of symptoms, were bilateral (94%), presenting severe intensity (53%) and a migraine phenotype (51%). Twelve patients (16.4%) presented with headache triggered by coughing. Eleven (15%) patients reported a continuous headache. Twenty-eight patients (38.4%) presented with anosmia and 29 (39.7%) with ageusia. Patients who reported hyposmia/anosmia and/or hypogeusia/ageusia experienced headache more frequently than those without these symptoms (OR: 5.39; 95% CI:1.66-17.45; logistic regression). Patients with anosmia and ageusia presented headache associated with phonophobia more often compared to those with headache without these complaints (Chi-square test; p < 0.05). Headache associated with COVID-19 presented a migraine phenotype more frequently in those experiencing previous migraine (p < 0.05). CONCLUSION: Headaches associated with COVID-19 are frequent, are generally severe, diffuse, present a migraine phenotype and are associated with anosmia and ageusia.

Headache: A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution.

OBJECTIVE: To define headache characteristics and evolution in relation to COVID-19 and its inflammatory response. METHODS: This is a prospective study, comparing clinical data and inflammatory biomarkers of COVID-19 patients with and without headache, recruited at the Emergency Room. We compared baseline with 6-week follow-up to evaluate disease evolution. RESULTS: Of 130 patients, 74.6% (97/130) had headache. In all, 24.7% (24/97) of patients had severe pain with migraine-like features. Patients with headache had more anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Clinical duration of COVID-19 was shorter in the headache group (23.9 ± 11.6 vs. 31.2 ± 12.0 days; p = 0.028). In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. After 6 weeks, of 74 followed-up patients with headache, 37.8% (28/74) had ongoing headache. Of these, 50% (14/28) had no previous headache history. Headache was the prodromal symptom of COVID-19 in 21.4% (6/28) of patients with persistent headache (p = 0.010). CONCLUSIONS: Headache associated with COVID-19 is a frequent symptom, predictive of a shorter COVID-19 clinical course. Disabling headache can persist after COVID-19 resolution. Pathophysiologically, its migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia.

Phenotypic characterization of acute headache attributed to SARS-CoV-2: An ICHD-3 validation study on 106 hospitalized patients.

INTRODUCTION: Headache is a common symptom of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we aimed to characterize the phenotype of headache attributed to SARS-CoV-2 infection and to test the International Classification of Headache Disorders (ICHD-3) phenotypic criteria for migraine and tension-type headache. METHODS: The study design was a cross-sectional study nested in a cohort. We screened all consecutive patients that were hospitalized and had a positive SARS-CoV-2 test. We included patients that described headache if the headache was not better explained by another ICHD-3 diagnosis. Patients were interviewed by two neurologists. RESULTS: We screened 580 patients and included 130 (mean age 56 years, 64% female). Headache was the first symptom of the infection in 26% of patients and appeared within 24 hours in 62% of patients. The headache was bilateral in 85%, frontal in 83%, and with pressing quality in 75% of patients. Mean intensity was 7.1, being severe in 64%. Hypersensitivity to stimuli occurred in 57% of patients. ICHD-3 criteria for headache attributed to systemic viral infection were fulfilled by 94% of patients; phenotypic criteria for migraine were fulfilled by 25% of patients, and tension-type headache criteria by 54% of patients. CONCLUSION: Headache attributed to SARS-CoV-2 infection in hospitalized patients has severe intensity, frontal predominance and oppressive quality. It occurs early in the course of the disease. Most patients fulfilled ICHD-3 criteria for headache attributed to systemic viral infection; however, the phenotype might resemble migraine in a quarter of cases and tension-type headache in half of the patients.

Characteristics of headache attributed to COVID-19 infection and predictors of its frequency and intensity: A cross sectional study.

OBJECTIVE: To study the characteristics of headache attributed to COVID-19 infection and predictors of its severity. METHODS: A cross-sectional study involved 172 individuals who had headache due to COVID-19 infection. A detailed analysis of such headache was done through a face-to-face interview. Patients with any other form of secondary headache were excluded. Labs, including lymphocytic count, C-reactive protein, D-dimer and ferritin and chest imaging, were made available. RESULTS: THE: majority of our patients had a diffuse headache (52.9%). It was pressing in 40.7%, with median intensity of 7 (assessed by visual analogue scale) and median frequency of 7 days/week. Patients with preexisting primary headache (52.9%) had significantly more frequent COVID-19 related headache than those without (47.1%) (p = 0.001). Dehydrated patients (64.5%) had more frequent COVID-19 related headache than those who were not dehydrated (35.5%) (p = 0.029). Patients with fever (69.8%) had significantly higher frequency and intensity of COVID-19 related headache compared to those without fever (30.2%) (p = 0.003, 0.012). Patients with comorbidities (19.8%) had significantly higher frequency and intensity of headache than those without comorbidities (80.2%) (p = 0.006, 0.003). After multiple linear regression, primary headache disorders, dehydration and comorbidities were considered predictors of frequency of COVID-19 related headache. Meanwhile, fever and dehydration were predictors of pain intensity. CONCLUSION: Healthcare providers of COVID-19 patients need to be aware of frequency and intensity predictors of COVID-19 related headache: Primary headache disorders, fever, dehydration, and comorbidities.