Could SARS-CoV-2 Infection Be a Novel Risk Factor for Multiple Sclerosis?

The outbreak of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has challenged the healthcare community worldwide. The SARS-CoV-2 primarily affects the respiratory system; however, strong evidence suggests that SARS-CoV-2 can be neuroinvasive, resulting in several neurological complications. It was previously assumed that some coronaviruses are involved in multiple sclerosis (MS) pathology via various mechanisms. The mechanisms involved in coronavirus-induced central demyelination are complex and largely redundant. Molecular mimicry was proposed to be one of the possible mechanisms. Disruption of the blood-brain barrier, dysregulation in several inflammatory cytokines, and upregulation of matrix metalloproteinases were also thought to induce central demyelinating pathology. This raises a question about the possible role of SARS-CoV-2 as a novel risk factor for MS.

Neuropsychiatric post-acute sequelae of COVID-19: prevalence, severity, and impact of vaccination.

The potential long-term neuropsychiatric effects of COVID-19 are of global concern. This study aimed to determine the prevalence and predictors of neuropsychiatric post-acute sequelae of COVID-19 among Egyptian COVID-19 survivors and to study the impact of full vaccination before COVID-19 infection on the occurrence and severity of these manifestations. Three months after getting COVID-19 infection, 1638 COVID-19 survivors were screened by phone for possible neuropsychiatric sequelae. Subjects suspected to suffer from these sequelae were invited to a face-to-face interview for objective evaluation. They were requested to rate the severity of their symptoms using visual analogue scales (VAS). The mean age of participants was 38.28 ± 13 years. Only 18.6% were fully vaccinated before COVID-19 infection. Neuropsychiatric post-acute sequelae of COVID-19 were documented in 598 (36.5%) subjects, fatigue was the most frequent one (24.6%), followed by insomnia (16.4%), depression (15.3%), and anxiety (14.4%). Moderate and severe COVID-19 infection and non-vaccination increased the odds of developing post-COVID-19 neuropsychiatric manifestations by 2 times (OR 1.95, 95% CI = 1.415-2.683), 3.86 times (OR 3.86, 95% CI = 2.358-6.329), and 1.67 times (OR 1.67, 95% CI = 1.253-2.216), respectively. Fully vaccinated subjects before COVID-19 infection (n = 304) had significantly lesser severity of post-COVID-19 fatigue, ageusia/hypogeusia, dizziness, tinnitus, and insomnia (P value = 0.001, 0.008, < 0.001, 0.025, and 0.005, respectively) than non-vaccinated subjects. This report declared neuropsychiatric sequelae in 36.5% of Egyptian COVID-19 survivors, fatigue being the most prevalent. The effectiveness of COVID-19 vaccines in reducing the severity of some post-COVID-19 neuropsychiatric manifestations may improve general vaccine acceptance.

Epidemiological aspects of headache after different types of COVID-19 vaccines: An online survey.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine-related side effects are a key concern with the emergence of various types of vaccines in the market. We aimed to assess the frequency and characteristics of headache following different types of COVID-19 vaccines. METHODS: Fully vaccinated people were recruited by a convenience sample through an online survey from September 1 to December 1, 2021. Detailed analysis of headache following vaccination was investigated. Participants with a history of pre-existing headaches were telephone interviewed by a neurologist to ascertain the type of headache. RESULTS: A total of 1372 participants participated (mean age 32.9 ± 11.1). The highest frequency of headache was reported with the adenoviral vector type (302/563, 53.6%), followed by mRNA vaccines (129/269, 48%) and then the inactivated type (188/540, 34.8%). Recipients of the adenoviral vector type had a significantly longer latency between vaccination and the headache onset (median 8 h [5:12]) than recipients of the inactivated type (median 4 h [2:8], p < 0.001). Headache intensity was significantly higher with the adenoviral vector type (median 6 [5:8]) than with the inactivated type (median 5 [4:7], p < 0.001). Adenoviral vector vaccines would increase the likelihood of headache by 2.38 times more than inactivated vaccines (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.83-3.04, p < 0.001). Female sex and thyroid disease were significantly associated with headache related to COVID-19 vaccines (OR 1.52, 95% CI 1.16-1.99; OR 3.97, 95% CI 1.55-10.2, respectively). CONCLUSION: Recipients of the COVID-19 vaccine should be counseled that they may experience headaches, especially after the adenoviral vector type. However, the intensity of such headache is mild to moderate and can resolve within a few days. Based on the current study design and the potential recall bias, these results may not be generalizable and should be preliminary.

Characteristics and Risk Factors of Persistent Neuropathic Pain in Recovered COVID-19 Patients.

OBJECTIVES: To assess risk factors for persistent neuropathic pain in subjects recovered from coronavirus disease 2019 (COVID-19) and to study the serum level of neurofilament light chain (NFL) in those patients. DESIGN: Case-control study. SETTING: Persistent post-COVID-19 pain. SUBJECTS: In total, 45 patients with post-COVID-19 pain and another 45 age and sex-matched healthcare workers who recovered from COVID-19 without pain. METHODS: The included participants were subjected to medical history taking, screening for depressive disorders, comprehensive neurological examination, and pain evaluation using the Douleur Neuropathique en 4 questions (DN4). All patients who had a score at least 4/10 on DN4 were included. The serum NFL level was measured for both groups at the time of patients' enrollment. RESULTS: The frequency of depression, moderate and severe COVID-19 cases, disease duration and serum ferritin were significantly higher in the cases with post-COVID-19 pain than controls. Binary logistic regression revealed that depression, azithromycin use, moderate and severe COVID-19 increased the odds of post-COVID-19 pain by 4.462, 5.444, 4.901, and 6.276 times, respectively. Cases with post-COVID-19 pain had significantly higher NFL (11.34 ± 9.7, 95% confidence interval [CI]: 8.42-14.25) than control group (7.64 ± 5.40, 95% CI: 6.02-9.27), (P value = .029). Patients with allodynia had significantly higher NFL (14.96 ± 12.41, 95% CI: 8.58-21.35) compared to those without (9.14 ± 6.99, 95% CI: 6.43-11.85) (P value = .05). DISCUSSION: Depression, azithromycin, and moderate and severe COVID-19 are independent predictors of persistent post-COVID-19 pain. Serum NFL may serve as a potential biomarker for persistent neuropathic pain after COVID-19.

Physical and Mental Fatigue in Subjects Recovered from COVID-19 Infection: A Case-Control Study.

PURPOSE: Much effort has been directed toward studying COVID-19 symptoms; however, the post-COVID-19 phase remains mysterious. The aim of this work was to conduct a clinical and neurophysiological evaluation of physical and mental fatigue in COVID-19 long-haulers and to study whether markers of COVID-19 severity are able to predict the likelihood of developing postinfectious fatigue syndrome (PIFS) in such patients. PATIENTS AND METHODS: This case-control study was conducted on 46 COVID-19 long-haulers who met the criteria for PIFS and 46 recovered COVID-19 subjects without any residuals. Clinical assessment of fatigue was done using a fatigue questionnaire. Repetitive nerve stimulation and single-fiber electromyography were done after excluding neuropathy and myopathy. RESULTS: The median value for physical fatigue was 4 (IQR 2-7), while that for mental fatigue was 2 (IQR 0-3). Each day's increase in the period of COVID-19 illness increased the odds of PIFS in COVID-19 long-haulers 1.104-fold, and each unit increase in ferritin increased the odds of PIFS 1.006-fold. A significant decrement in at least one muscle was observed in 50% of patients. Patients with PIFS had significantly higher mean consecutive difference (MCD) in the extensor digitorum communis than the control group. There were statistically significant positive correlations between MCD values and physical, mental, and total fatigue scores. CONCLUSION: Higher ferritin levels and prolonged COVID-19 infection were independent predictors of PIFS in COVID-19 long-haulers. There was electrophysiological evidence of abnormalities in the peripheral portion of the motor unit in COVID-19 long-haulers with PIFS.

Neurological Manifestations in a Cohort of Egyptian Patients with COVID-19: A Prospective, Multicenter, Observational Study.

BACKGROUND: The COVID-19 pandemic has reached over 276 million people globally with 5.3 million deaths as of 22nd December 2021. COVID-19-associated acute and long-term neurological manifestations are well recognized. The exact profile and the timing of neurological events in relation to the onset of infection are worth exploring. The aim of the current body of work was to determine the frequency, pattern, and temporal profile of neurological manifestations in a cohort of Egyptian patients with confirmed COVID-19 infection. METHODS: This was a prospective study conducted on 582 hospitalized COVID-19 patients within the first two weeks of the diagnosis of COVID-19 to detect any specific or non-specific neurological events. RESULTS: The patients' mean (SD) age was 46.74 (17.26) years, and 340 (58.42%) patients were females. The most commonly encountered COVID-19 symptoms were fever (90.72%), cough (82.99%), and fatigue (76.98%). Neurological events (NE) detected in 283 patients (48.63%) and were significantly associated with a severe COVID-19 at the onset (OR: 3.13; 95% CI: 2.18-4.51; p < 0.0001) and with a higher mortality (OR: 2.56; 95% CI: 1.48-5.46; p = 0.019). The most frequently reported NEs were headaches (n = 167) and myalgias (n = 126). Neurological syndromes included stroke (n = 14), encephalitis (n = 12), encephalopathy (n = 11), transverse myelitis (n = 6) and Guillain-Barré syndrome (n = 4). CONCLUSIONS: Neurological involvement is common (48.63%) in COVID-19 patients within the first two weeks of the illness. This includes neurological symptoms such as anosmia, headaches, as well as a constellation of neurological syndromes such as stroke, encephalitis, transverse myelitis, and Guillain-Barré syndrome. Severity of acute COVID-19 illness and older age are the main risk factors.

Risk estimation of SUDEP during COVID-19 pandemic era in a tertiary referral center.

OBJECTIVE: No data exist regarding the impact of the lockdown due to the COVID-19 pandemic on the risk factors of sudden unexpected death in epilepsy (SUDEP). This study aimed to stratify risk factors of SUDEP in relation to COVID-19 lockdown, among patients with epilepsy (PWE) in Cairo University epilepsy unit (CUEU). Therefore, we can detect risk factors and mitigate such factors in the second wave of the virus. METHODS: an observational, cross-sectional study carried on 340 Egyptian patients with active epilepsy. Individual risk identification and stratification was done by using The SUDEP and seizure Safety Checklist, after which sharing risk knowledge to PWE and their caregivers was undertaken. RESULTS: The mean age of patients was 29.72 ± 12.12. The median of the static factors was 4 (IQR 3-5) whereas, the median of the modifiable factors was 2 (IQR 1-3). Epilepsy emergencies (serial seizures or status epilepticus) were reported in 24.1 % of patients, for which non-compliance was the commonest cause, followed by deferral of epilepsy surgery for patients with drug resistant epilepsy (DRE). Stepwise logistic regression analysis showed that use of anxiolytic medications, non-compliance, keeping patients with DRE on dual anti-seizure medications (ASMs), or adding third medication increased the odds of increased seizure frequency by 2.7, 3.5, 16.6 and 6.1 times, respectively. CONCLUSION: Some COVID-19 related issues had influenced the risk of seizure worsening including postponing epilepsy surgery for patients with DRE, non-compliance, and psychiatric comorbidities. Special attention should be paid to these issues to mitigate the risk of SUDEP.

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.

Relative Frequency and Risk Factors of COVID-19 Related Headache in a Sample of Egyptian Population: A Hospital-Based Study.

OBJECTIVES: Headache is considered one of the most frequent neurological manifestations of coronavirus disease 2019 (COVID-19). This work aimed to identify the relative frequency of COVID-19-related headache and to clarify the impact of clinical, laboratory findings of COVID-19 infection on headache occurrence and its response to analgesics. DESIGN: Cross-sectional study. SETTING: Recovered COVID-19 patients. SUBJECTS: In total, 782 patients with a confirmed diagnosis of COVID-19 infection. METHODS: Clinical, laboratory, and imaging data were obtained from the hospital medical records. Regarding patients who developed COVID-19 related headache, a trained neurologist performed an analysis of headache and its response to analgesics. RESULTS: The relative frequency of COVID-19 related headache among our sample was 55.1% with 95% confidence interval (CI) (.516-.586) for the estimated population prevalence. Female gender, malignancy, primary headache, fever, dehydration, lower levels of hemoglobin and platelets and higher levels of neutrophil/lymphocyte ratio (NLR) and CRP were significantly associated with COVID-19 related headache. Multivariate analysis revealed that female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count were independent predictors of headache occurrence. By evaluating headache response to analgesics, old age, diabetes, hypertension, primary headache, severe COVID-19, steroid intake, higher CRP and ferritin and lower hemoglobin levels were associated with poor response to analgesics. Multivariate analysis revealed that primary headache, steroids intake, moderate and severe COVID-19 were independent predictors of non-response to analgesics. DISCUSSION: Headache occurs in 55.1% of patients with COVID-19. Female gender, fever, dehydration, primary headache, high NLR, and decreased platelet count are considered independent predictors of COVID-19 related headache.

Management Strategies of Patients with Neuromyelitis Optica Spectrum Disorder During the COVID-19 Pandemic Era.

The ongoing coronavirus (COVID-19) pandemic is a global health emergency of international concern and has affected management plans of many autoimmune disorders. Immunosuppressive and immunomodulatory therapies are pivotal in the management of neuromyelitis optica spectrum disorder (NMOSD), potentially placing patients at an increased risk of contracting infections such as COVID-19. The optimal management strategy of NMOSD during the COVID-19 era remains unclear. Here, however, we examined the evidence of NMOSD disease-modifying therapies (DMTs) use during the present period and highlighted different scenarios including treatment of relapses as well as initiation and maintenance of DMTs in order to optimize care of NMOSD patients in the COVID-19 era.