COVID-19-Induced Stroke and the Potential of Using Mesenchymal Stem Cells-Derived Extracellular Vesicles in the Regulation of Neuroinflammation.

Ischemic stroke (IS) is a known neurological complication of COVID-19 infection, which is associated with high mortality and disability. Following IS, secondary neuroinflammation that occurs can play both harmful and beneficial roles and lead to further injury or repair of damaged neuronal tissue, respectively. Since inflammation plays a pivotal role in the pathogenesis of COVID-19-induced stroke, targeting neuroinflammation could be an effective strategy for modulating the immune responses following ischemic events. Numerous investigations have indicated that the application of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) improves functional recovery following stroke, mainly through reducing neuroinflammation as well as promoting neurogenesis and angiogenesis. Therefore, MSC-EVs can be applied for the regulation of SARS-CoV-2-mediated inflammation and the management of COVID-19- related ischemic events. In this study, we have first described the advantages and disadvantages of neuroinflammation in the pathological evolution after IS and summarized the characteristics of neuroinflammation in COVID-19-related stroke. Then, we have discussed the potential benefit of MSC-EVs in the regulation of inflammatory responses after COVID-19-induced ischemic events.

Guillain-Barré syndrome in association with COVID-19 vaccination: a systematic review.

Since the beginning of worldwide vaccination against coronavirus disease 2019 (COVID-19), studies have reported a possible association between vaccination and Guillain-Barré syndrome (GBS). In this regard, we conducted a systematic review assessing different demographic, clinical, and neurophysiological aspects of patients with GBS following immunization with COVID-19 vaccines. A comprehensive search of PubMed, Web of Science, Scopus, and Google Scholar was performed. Articles in English between January 2020 and November 2021 were included. Data on demographics, clinical characteristics, vaccines information, treatment approaches, and outcomes were extracted. The data of a total of 88 patients out of 41 studies was included. The mean age of patients was 58.7 ± 16.6 years and 55 cases (62.5%) were male. AstraZeneca was the most-reported vaccine associated with GBS with 52 cases (59.1%) followed by Pfizer with 20 cases (22.7%). GBS occurred after the first dose of vaccination in 70 cases (79.5%). The mean time interval between vaccination and symptom onset was 13.9 ± 7.4 days. Limb weakness (47.7%), sensory disturbance (38.6%), and facial weakness (27.3%) were the most common reported symptoms, respectively. Albuminocytologic dissociation was seen in 65% of patients who underwent lumbar puncture (n = 65). Acute inflammatory demyelinating polyradiculopathy was the most common GBS subtype, which was reported in 38 patients (43.2%). While one-fifth of patients underwent intubation (n = 17), a favorable outcome was achieved in the majority of subjects (n = 46, 63%). Overall, a small rise in GBS incidence, following various COVID-19 vaccines, was observed. Notably, 85% of affected individuals experienced at least a partial recovery.

Status epilepticus and the presence of SARS-COV-2 in the cerebrospinal fluid: A case report.

A growing number of studies indicate a broad range of neurological manifestations, including seizures, occur in patients with COVID-19 infection. We report a 29-year-old female patient with status epilepticus and positive SARS-CoV-2 in the cerebrospinal fluid. Our findings support previous reports suggesting seizure as a possible symptom of COVID-19 infection.

The association between micronutrients and the SARS-CoV-2-specific antibodies in convalescent patients.

BACKGROUND: Various micronutrients play key roles in the immune responses to viral infection, antibody synthesis, and susceptibility to infection. This study aimed to investigate the role of micronutrients on the immune responses following SARS-CoV-2 infection. METHODS: To evaluate humoral immunity following SARS-CoV-2 infection, the levels of SARS-CoV-2-specific IgM and IgG, as well as the concentrations of different micronutrients, were determined in 36 convalescent COVID-19 patients 60 days after infection. Furthermore, the correlation between biochemical and hematological parameters, clinical features, and the changes in adiposity with SARS-CoV-2 antibodies was evaluated. RESULTS: Serum IgM and IgG antibodies were detected in 38.8% and 83.3% of recovered patients after 60 days of COVID-19 infection, respectively. The values of SARS-CoV-2-specific IgG were negatively correlated with the number of the platelet. Moreover, the values of SARS-CoV-2-specific IgM were positively correlated with LDH and the vitamin B12 concentration. Furthermore, a gender-specific association of SARS-CoV-2-specific IgG and IgM with vitamins D as well as with B9 and zinc was observed. A significant negative correlation was observed between the values of IgG with vitamin D in male participants and a positive correlation was detected between IgG values and B9 in female participants. Moreover, IgM levels with serum zinc values in females were negatively correlated. CONCLUSION: Our study suggests the potential role of micronutrients in gender-specific humoral immunity following SARS-CoV-2 infection. Further studies are required with a greater sample of subjects to substantiate the validity and robustness of our findings.

SARS-CoV-2 may trigger inflammasome and pyroptosis in the central nervous system: a mechanistic view of neurotropism.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the central nervous system and cause several neurological manifestations. Data from cerebrospinal fluid analyses and postmortem samples have been shown that SARS-CoV-2 has neuroinvasive properties. Therefore, ongoing studies have focused on mechanisms involved in neurotropism and neural injuries of SARS-CoV-2. The inflammasome is a part of the innate immune system that is responsible for the secretion and activation of several pro-inflammatory cytokines, such as interleukin-1ß, interleukin-6, and interleukin-18. Since cytokine storm has been known as a major mechanism followed by SARS-CoV-2, inflammasome may trigger an inflammatory form of lytic programmed cell death (pyroptosis) following SARS-CoV-2 infection and contribute to associated neurological complications. We reviewed and discussed the possible role of inflammasome and its consequence pyroptosis following coronavirus infections as potential mechanisms of neurotropism by SARS-CoV-2. Further studies, particularly postmortem analysis of brain samples obtained from COVID-19 patients, can shed light on the possible role of the inflammasome in neurotropism of SARS-CoV-2.

Detection of SARS-coronavirus-2 in the central nervous system of patients with severe acute respiratory syndrome and seizures.

This study was designed to evaluate whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can directly target the central nervous system (CNS). We present four patients suffering from the loss of consciousness and seizure during the clinical course of COVID-19 infection. In addition to positive nasopharyngeal swab tests, SARS-CoV-2 has been detected in their cerebrospinal fluid. This report indicates the neuroinvasive potential of SARS-CoV-2, suggesting the ability of this virus to spread from the respiratory tract to the CNS.

COVID-19 pandemic: the possible influence of the long-term ignorance about climate change.

In addressing the current COVID-19 pandemic and evaluating the measures taken by global leaders so far, it is crucial to trace back the circumstances influencing the emergence of the crisis that the world is presently facing. Could it be that the failure to act in a timely manner dates way back to when first concerns about climate change and its inevitable threat to human health came up? Multiple lines of evidence suggest that the large-scale and rapid environmental changes in the last few decades may be implicated in the emergence of COVID-19 pandemic by increasing the potential risk of the occurrence and the spread of zoonotic diseases, worsening food security, and weakening the human immune system. As we are facing progressive climatic change, a failure to act accordingly could inevitably lead to further, more frequent confrontations with newly emerging diseases.

Potential roles of micronutrient deficiency and immune system dysfunction in the coronavirus disease 2019 (COVID-19) pandemic.

Preliminary studies indicate that a robust immune response across different cell types is crucial in recovery from coronavirus disease 2019 (COVID-19). An enormous number of investigations point to the vital importance of various micronutrients in the interactions between the host immune system and viruses, including COVID-19. There are complex and multifaceted links among micronutrient status, the host immune response, and the virulence of pathogenic viruses. Micronutrients play a critical role in the coordinated recruitment of innate and adaptive immune responses to viral infections, particularly in the regulation of pro- and anti-inflammatory host responses. Furthermore, inadequate amounts of micronutrients not only weaken the immune system in combating viral infections, but also contribute to the emergence of more virulent strains via alterations of the genetic makeup of the viral genome. The aim of this study was to evaluate the evidence that suggests the contribution of micronutrients in the spread as well as the morbidity and mortality of COVID-19. Both the presence of micronutrient deficiencies among infected individuals and the effect of micronutrient supplementation on the immune responses and overall outcome of the disease could be of great interest when weighing the use of micronutrients in the prevention and treatment of COVID-19 infection. These investigations could be of great value in dealing with future viral epidemics.

A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View.

There is increasing evidence of neurological manifestations and complications in patients with coronavirus disease 19 (COVID-19). More than one-quarter of patients with COVID-19 developed various neurological symptoms, ranging from headache and dizziness to more serious medical conditions, such as seizures and stroke. The recent investigations introduced hyposmia as a potential early criterion of infection with COVID-19. Despite the high mortality and morbidity rate of COVID-19, its exact mechanism of action and pathogenesis is not well characterized. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells. In the present study, we reviewed the most common neurological manifestations and complications that emerged after infection with the SARS-CoV-2 and discussed their possible relation to the expression and function of ACE2. Comprehensive and detailed studies are required to uncover how this virus invades the neural system as well as other critical organs.