The Possible Role of COVID-19 in the Triggering of Underlying Mitochondrial Dysfunction in MELAS Syndrome, A Brief Report of three cases.

BACKGROUND: During corona virus pandemic, various neurological complications of COVID-19 have been reported. Recent studies demonstrated different pathophysiology for neurological manifestations of COVID-19 such as mitochondrial dysfunction and damage to cerebral vasculature. In addition, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder with a variety of neurological symptoms. In this study, we aim to assess a potential predisposition in mitochondrial dysfunction of COVID-19, leading to MELAS presentation. METHODS: We studied three previously healthy patients with the first presentation of acute stroke-like symptoms, following COVID-19 infection. We analyzed the patients' clinical data and brain magnetic resonance imaging (MRI) lesions that presented to the neurological center of a university-affiliated hospital in Tehran, Iran, from September 2020 to August 2021. RESULTS: All cases are characterized by a temporoparietal abnormality in imaging studies and electroencephalogram (EEG). Based on electrodiagnostic tests, three patients were diagnosed with myopathy. In two brothers with relatively the same symptoms, one performed muscle biopsy finding myopathic process, and genetic testing confirmed a 3243A>G point mutation in a heteroplasmic state in one of our patients. CONCLUSION: Although MELAS is not a prevalent condition, the recent increase in the number of these patients in our center might indicate the potential role of COVID-19 in triggering the silent pre- existing mitochondrial dysfunction in these patients.

The Role of Anxiety and Cortisol in Outcomes of Patients With Covid-19

Introduction: The outbreak due to Coronavirus Disease 2019 (COVID-19) is n global public health emergency and challenges psychological resilience. The central nervous system, endocrine system, and immune system are complex interacting systems. Cortisol has been implicated as the cause of a wide range of mental and physical health disorders;however, the impact of cortisol on outcomes in patients with COVID-19 is not clear.Methods: The current study enrolled patients with COVID-19 (onset of disease within 7 days of the first symptom) to evaluate the serum concentration of cortisol and levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) to investigate a possible relationship between cortisol, depression, and anxiety levels and outcomes of patients with COVID-19.Results: A total of 30 patients with COVID-19 were studied. The levels of cortisol and HADS score in patients who died of Covid-19 were significantly higher in comparison with surviving patients (P<0.017 and P<0.001 respectively). We also found that the HADS score was positively correlated with serum cortisol levels (r= 0.842, P=0.004).Conclusion: Our findings showed that stress and anxiety are associated with patients' outcomes. Psychological interventions can improve the mental health of vulnerable groups during the COVID-19 epidemic.

Inflammatory Response Leads to Neuronal Death in Human Post-Mortem Cerebral Cortex in Patients with COVID-19.

The recent coronavirus disease of 2019 (COVID-19) pandemic has adversely affected people worldwide. A growing body of literature suggests the neurological complications and manifestations in response to COVID-19 infection. Herein, we explored the inflammatory and immune responses in the post-mortem cerebral cortex of patients with severe COVID-19. The participants comprised three patients diagnosed with severe COVID-19 from March 26, 2020, to April 17, 2020, and three control patients. Our findings demonstrated a surge in the number of reactive astrocytes and activated microglia, as well as low levels of glutathione along with the upregulation of inflammation- and immune-related genes IL1B, IL6, IFITM, MX1, and OAS2 in the COVID-19 group. Overall, the data imply that oxidative stress may invoke a glial-mediated neuroinflammation, which ultimately leads to neuronal cell death in the cerebral cortex of COVID-19 patients.

Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19.

As the SARS-COV-2 becomes a global pandemic, many researchers have a concern about the long COVID-19 complications. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a persistent, debilitating, and unexplained fatigue disorder. We investigated psychological morbidities such as CFS and post-traumatic stress disorder (PTSD) among survivors of COVID-19 over 6 months. All COVID-19 survivors from the university-affiliated hospital of Tehran, Iran, were assessed 6 months after infection onset by a previously validated questionnaire based on the Fukuda guidelines for CFS/EM and DSM-5 Checklist for PTSD (The Post-traumatic Stress Disorder Checklist for DSM-5 or PCL-5) to determine the presence of stress disorder and chronic fatigue problems. A total of 120 patients were enrolled. The prevalence rate of fatigue symptoms was 17.5%. Twelve (10%) screened positive for chronic idiopathic fatigue (CIF), 6 (5%) for CFS-like with insufficient fatigue syndrome (CFSWIFS), and 3 (2.5%) for CFS. The mean total scores in PCL-5 were 9.27 ± 10.76 (range:0-44), and the prevalence rate of PTSD was 5.8%. There was no significant association after adjusting between CFS and PTSD, gender, comorbidities, and chloroquine phosphate administration. The obtained data revealed the prevalence of CFS among patients with COVID-19, which is almost similar to CFS prevalence in the general population. Moreover, PTSD in patients with COVID-19 is not associated with the increased risk of CFS. Our study suggested that medical institutions should pay attention to the psychological consequences of the COVID-19 outbreak.

COVID-19, de novo seizures, and epilepsy: a systematic review.

OBJECTIVE: We discuss the evidence on the occurrence of de novo seizures in patients with COVID-19, the consequences of this catastrophic disease in people with epilepsy (PWE), and the electroencephalographic (EEG) findings in patients with COVID-19. METHODS: This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. MEDLINE, Scopus, and Embase from inception to August 15, 2020 were systematically searched. These key words were used: "COVID" AND "seizure" OR "epilepsy" OR "EEG" OR "status epilepticus" OR "electroencephalography". RESULTS: We could identify 62 related manuscripts. Many studies were case reports or case series of patients with COVID-19 and seizures. PWE showed more psychological distress than healthy controls. Many cases with new-onset focal seizures, serial seizures, and status epilepticus have been reported in the literature. EEG studies have been significantly ignored and underused globally. CONCLUSION: Many PWE perceived significant disruption in the quality of care to them, and some people reported increase in their seizure frequency since the onset of the pandemic. Telemedicine is a helpful technology that may improve access to the needed care for PWE in these difficult times. De novo seizures may occur in people with COVID-19 and they may happen in a variety of forms. In addition to prolonged EEG monitoring, performing a through metabolic investigation, electrocardiogram, brain imaging, and a careful review of all medications are necessary steps. The susceptibility of PWE to contracting COVID-19 should be investigated further.

The outbreak of methanol intoxication during COVID-19 pandemic: prevalence of brain lesions and its predisposing factors.

During the COVID-19 pandemic, methanol-containing beverages' consumption has risen because people mistakenly believed that alcohol might protect them against the virus. This study aimed to evaluate the prevalence and predisposing factors of brain lesions in patients with methanol toxicity and its outcome. A total of 516 patients with confirmed methanol poisoning were enrolled in this retrospective study, of which 40 patients underwent spiral brain computed tomography (CT) scan. The presence of unilateral or bilateral brain necrosis was significantly higher in the non-survival group (p = 0.001). Also, intracerebral hemorrhage (ICH) and brain edema were prevalent among patients that subsequently died (p = 0.004 and p = 0.002, respectively). Lower Glasgow Coma Scale (GCS) was related to a higher mortality rate (p = 0.001). The mortality rate in chronic alcohol consumption was lower than the patients who drank alcohol for the first time (p = 0.014). In conclusion, increasing the number of methanol poisoning and its associated mortality and morbidity should be considered a threat during the COVID-19 pandemic.

The Role of Anxiety and Cortisol in Outcomes of Patients With Covid-19.

INTRODUCTION: The outbreak due to Coronavirus Disease 2019 (COVID-19) is n global public health emergency and challenges psychological resilience. The central nervous system, endocrine system, and immune system are complex interacting systems. Cortisol has been implicated as the cause of a wide range of mental and physical health disorders; however, the impact of cortisol on outcomes in patients with COVID-19 is not clear. METHODS: The current study enrolled patients with COVID-19 (onset of disease within 7 days of the first symptom) to evaluate the serum concentration of cortisol and levels of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) to investigate a possible relationship between cortisol, depression, and anxiety levels and outcomes of patients with COVID-19. RESULTS: A total of 30 patients with COVID-19 were studied. The levels of cortisol and HADS score in patients who died of Covid-19 were significantly higher in comparison with surviving patients (P<0.017 and P<0.001 respectively). We also found that the HADS score was positively correlated with serum cortisol levels (r= 0.842, P=0.004). CONCLUSION: Our findings showed that stress and anxiety are associated with patients' outcomes. Psychological interventions can improve the mental health of vulnerable groups during the COVID-19 epidemic.

Proinflammatory Cytokines in the Olfactory Mucosa Result in COVID-19 Induced Anosmia.

Studies have found increased rates of dysosmia in patients with Novel Coronavirus disease 2019 (COVID-19). However, the mechanism that causes olfactory loss is unknown. The primary objective of this study was to explore local proinflammatory cytokine levels in the olfactory epithelium in patients with COVID-19. Biopsies of the olfactory epithelium were taken from patients with confirmed COVID-19 as well as uninfected controls. Levels of tumor necrosis factor α (TNF-α) and interleukin-1-beta (IL-1ß) were assessed using ELISA and compared between groups. Average TNF-α levels were significantly increased in the olfactory epithelium of the COVID-19 group compared to the control group (P < 0.05). However, no differences in IL-1ß were seen between groups. Elevated levels of the proinflammatory cytokine TNF-α were seen in the olfactory epithelium in patients with COVID-19. This suggests that direct inflammation of the olfactory epithelium could play a role in the acute olfactory loss described in many patients with COVID-19.

Central nervous system manifestations of COVID-19: A systematic review.

OBJECTIVE: In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19. METHODS: MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: "COVID 19" OR "coronavirus" AND "brain" OR "CNS" OR "neurologic". RESULTS: Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general. CONCLUSION: While neurological manifestations of COVID-19 have not been studied appropriately, it is highly likely that some of these patients, particularly those who suffer from a severe illness, have CNS involvement and neurological manifestations. Precise and targeted documentation of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.