Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an emergent infectious disease that has caused millions of deaths throughout the world. COVID-19 infection’s main symptoms are fever, cough, fatigue, and neurological manifestations such as headache, myalgias, anosmia, ageusia, impaired consciousness, seizures, and even neuromuscular junctions’ disorders. In addition, it is known that this disease causes a series of systemic complications such as adverse respiratory distress syndrome, cardiac injury, acute kidney injury, and liver dysfunction. Due to the neurological symptoms associated with COVID-19, damage in the central nervous system has been suggested as well as the neuroinvasive potential of SARS-CoV-2. It is known that CoV infections are associated with an inflammation process related to the imbalance of the antioxidant system; cellular changes caused by oxidative stress contribute to brain tissue damage. Although anti-COVID-19 vaccines are under development, there is no specific treatment for COVID-19 and its clinical manifestations and complications; only supportive treatments with immunomodulators, anti-vascular endothelial growth factors, modulating drugs, statins, or nutritional supplements have been used. In the present work, we analyzed the potential of antioxidants as adjuvants for the treatment of COVID-19 and specifically their possible role in preventing or decreasing the neurological manifestations and neurological complications present in the disease.

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SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

International Journal of Molecular Sciences ◽

10.3390/ijms21155475 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5475 ◽

Cited By ~ 11

Author(s):

Manuela Pennisi ◽

Giuseppe Lanza ◽

Luca Falzone ◽

Francesco Fisicaro ◽

Raffaele Ferri ◽

...

Keyword(s):

Nervous System ◽

Molecular Mechanisms ◽

Neuronal Damage ◽

Neurological Complications ◽

Neurological Manifestations ◽

Wide Range ◽

Inflammatory State ◽

Acute Polyneuropathy ◽

The Central Nervous System ◽

The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

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Revisiting the Molecular Mechanism of Neurological Manifestations in Antiphospholipid Syndrome: Beyond Vascular Damage

Journal of Immunology Research ◽

10.1155/2014/239398 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 15

Author(s):

M. Carecchio ◽

R. Cantello ◽

C. Comi

Keyword(s):

Basal Ganglia ◽

Antiphospholipid Syndrome ◽

Vascular System ◽

Clinical Manifestations ◽

Vascular Damage ◽

Coagulation System ◽

Neurological Manifestations ◽

Immune Mediated ◽

The Central Nervous System ◽

Multiorgan Disease

Antiphospholipid syndrome (APS) is a multiorgan disease often affecting the central nervous system (CNS). Typically, neurological manifestations of APS include thrombosis of cerebral vessels leading to stroke and requiring prompt initiation of treatment with antiplatelet drugs or anticoagulant therapy. In these cases, alterations of the coagulation system at various levels caused by multiple effects of antiphospholipid antibodies (aPL) have been postulated to explain the vascular damage to the CNS in APS. However, several nonvascular neurological manifestations of APS have progressively emerged over the past years. Nonthrombotic, immune-mediated mechanisms altering physiological basal ganglia function have been recently suggested to play a central role in the pathogenesis of these manifestations that include, among others, movement disorders such as chorea and behavioral and cognitive alterations. Similar clinical manifestations have been described in other autoimmune CNS diseases such as anti-NMDAR and anti-VGCK encephalitis, suggesting that the spectrum of immune-mediated basal ganglia disorders is expanding, possibly sharing some pathophysiological mechanisms. In this review, we will focus on thrombotic and nonthrombotic neurological manifestations of APS with particular attention to immune-mediated actions of aPL on the vascular system and the basal ganglia.

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The Health Implication of Enterohaemorrhagic Escherichia coli (EHEC) 0157:H7: A Review on Haemolytic Uraemic Syndrome

Asian Journal of Research in Medical and Pharmaceutical Sciences ◽

10.9734/ajrimps/2019/v7i430129 ◽

2019 ◽

pp. 1-10

Author(s):

Onengiyeofori Ibama ◽

Edna O. Ibegbulem ◽

Donatus Onwuli ◽

Adline Ben-Chioma

Keyword(s):

Escherichia Coli ◽

Haemolytic Anaemia ◽

Bacterial Strain ◽

Haemolytic Uraemic Syndrome ◽

Clinical Manifestations ◽

Specific Treatment ◽

Kidney Injury ◽

Electrolyte Imbalance ◽

Health Concern ◽

Enterohaemorrhagic Escherichia Coli

Consumption of foods, water, vegetables, fruits, undercooked/ground/raw meat, unpasteurized milk or milk products contaminated with the bacterium strain Escherichia coli 0157:H7 has become a serious public health concern. This strain naturally inhabits the digestive tract of healthy cattle, and is released into the environment through the faeces of the animal. This strain cause haemorrhagic enterocolitis or gastroenteritis, and then haemolytic uraemic syndrome (HUS). HUS is a disorder characterised by haemolytic anaemia, low platelet count and acute kidney failure, and this disorder is a consequence of the production and action of Shiga-like toxin produced mainly by this bacterial strain (accounting for 90 percent of all cases), and occurs mainly in children less than five (5) years of age, but also occurs in the elderly. After infection with this bacterial strain, the disorder begins with intestinal perforation and ulceration leading to bloody diarrhoea, and consequently acute kidney injury, thrombocytopenia and microangiopathic haemolytic anaemia. In conjunction with clinical manifestations, several laboratory investigations (haematological, biochemical and microbiological assays) are implicated in the diagnosis of HUS. There is currently no specific treatment for HUS; however, supportive care (such as treatment of hypertension, fluid and electrolyte imbalance, haemodialysis, blood transfusion, etc) happens to be the only ameliorative measure for this disorder.

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Altered mental status is a predictor of poor outcomes in COVID-19 patients: A cohort study

PLoS ONE ◽

10.1371/journal.pone.0258095 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258095

Author(s):

Abdallah S. Attia ◽

Mohammad Hussein ◽

Mohamed A. Aboueisha ◽

Mahmoud Omar ◽

Mohanad R. Youssef ◽

...

Keyword(s):

Mechanical Ventilation ◽

Cohort Study ◽

Mental Status ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Kidney Injury ◽

Altered Mental Status ◽

Neurological Manifestations ◽

Icu Admission ◽

Poor Outcomes

Introduction Several studies have described typical clinical manifestations, including fever, cough, diarrhea, and fatigue with COVID-19 infection. However, there are limited data on the association between the presence of neurological manifestations on hospital admission, disease severity, and outcomes. We sought to investigate this correlation to help understand the disease burden. Methods We delivered a multi-center retrospective study of positive laboratory-confirmed COVID-19 patients. Clinical presentation, laboratory values, complications, and outcomes data were reported. Our findings of interest were Intensive Care Unit (ICU) admission, intubation, mechanical ventilation, and in-hospital mortality. Results A total of 502 patients with a mean age of 60.83 ± 15.5 years, of them 71 patients (14.14%) presented with altered mental status, these patients showed higher odds of ICU admission (OR = 2.06, 95%CI = 1.18 to 3.59, p = 0.01), mechanical ventilation (OR = 3.28, 95%CI = 1.86 to 5.78, p < 0.001), prolonged (>4 days) mechanical ventilation (OR = 4.35, 95%CI = 1.89 to 10, p = 0.001), acute kidney injury (OR = 2.18, 95%CI = 1.28 to 3.74, p = 0.004), and mortality (HR = 2.82, 95%CI = 1.49 to 5.29, p = 0.01). Conclusion This cohort study found that neurological presentations are associated with higher odds of adverse events. When examining patients with neurological manifestations, clinicians should suspect COVID-19 to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.

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Rapidly progressive glomerulonephritis in children

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.38.icon-2022.5774 ◽

2021 ◽

Vol 38 (ICON-2022) ◽

Author(s):

Khemchand N Moorani ◽

Madiha Aziz ◽

Farhana Amanullah

Keyword(s):

Immune Complex ◽

Search Strategy ◽

Rapid Development ◽

Clinical Manifestations ◽

Specific Treatment ◽

Rapidly Progressive Glomerulonephritis ◽

Kidney Injury ◽

Antineutrophil Cytoplasmic Antibody ◽

Good Prognosis ◽

Cochrane Library

Rapidly progressive glomerulonephritis (RPGN), characterized by a rapid development of nephritis with loss of kidney function in days or weeks, is typically associated histologically, with crescents in most glomeruli; and is a challenging problem, particularly in low resource settings. RPGN is a diagnostic and therapeutic emergency requiring prompt evaluation and treatment to prevent poor outcomes. Histopathologically, RPGN consists of four major categories, anti-glomerular basement membrane (GBM) disease, immune complex mediated, pauci-immune disorders and idiopathic /overlap disorders. Clinical manifestations include gross hematuria, proteinuria, oliguria, hypertension and edema. Diagnostic evaluation, including renal function tests, electrolytes, urinalysis/microscopy and serology including (anti GBM antibody, antineutrophil cytoplasmic antibody (ANCA)) starts simultaneously with management. An urgent renal biopsy is required to allow specific pathologic diagnosis as well as to assess disease activity and chronicity to guide specific treatment. The current guidelines for management of pediatric RPGN are adopted from adult experience and consist of induction and maintenance therapy. Aggressive combination immunosuppression has markedly improved outcomes, however, nephrotic syndrome, severe acute kidney injury requiring dialysis, presence of fibrous crescents and chronicity are predictors of poor renal survival. RPGN associated post infectious glomerulonephritis (PIGN) usually has good prognosis in children without immunosuppression whereas immune-complex-mediated GN and lupus nephritis (LN) are associated with poor prognosis with development of end stage kidney disease (ESKD) in more than 50% and 30% respectively. Given the need for prompt diagnosis and urgent treatment to avoid devastating outcomes, we conducted a review of the latest evidence in RPGN management to help formulate clinical practice guidance for children in our setting.Information sources and search strategy: The search strategy was performed in the digital databases of PubMed, Cochrane Library, google scholar, from their inception dates to December 2020. Three investigators independently performed a systematic search using the following search terms “Rapidly progressive glomerulonephritis” “children” “crescentic glomerulonephritis” “management” at the same time, backtracking search for references of related literature. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5774 How to cite this:Moorani KN, Aziz M, Amanullah F. Rapidly progressive glomerulonephritis in children. Pak J Med Sci. 2022;38(2):417-425. doi: https://doi.org/10.12669/pjms.38.ICON-2022.5774 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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SARS-CoV-2 Impact on the Central Nervous System: Are Astrocytes and Microglia Main Players or Merely Bystanders?

10.20944/preprints202006.0319.v1 ◽

2020 ◽

Author(s):

Veronica Murta ◽

Alejandro Villarreal ◽

Alberto Javier Ramos

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Clinical Manifestations ◽

Signs And Symptoms ◽

Experimental Models ◽

Circumventricular Organs ◽

Target Cells ◽

Neurological Manifestations ◽

Cns Inflammation ◽

The Central Nervous System

With confirmed COVID-19 cases surpassing the 8.5 million mark around the globe, there is an imperative need to deepen the efforts from the international scientific community to gain comprehensive understanding of SARS-CoV-2. Although the main clinical manifestations are associated with respiratory or intestinal symptoms, reports of specific and non-specific neurological signs and symptoms, both at presentation or during the course of the acute phase, are increasing. Approximately 25-40% of the patients present neurological symptoms. The etiology of these neurological manifestations remains obscure, and probably involves several direct pathways, not excluding the direct entry of the virus to the Central Nervous System (CNS) through the olfactory epithelium, circumventricular organs, or disrupted blood-brain barrier (BBB). Furthermore, neuroinflammation might occur in response to the strong systemic cytokine storm described for COVID-19, or due to dysregulation of the CNS angiotensin system. Descriptions of neurological manifestations in patients in the previous coronavirus (CoV) outbreaks have been numerous for the SARS-CoV and lesser for MERS-CoV. Strong evidence from patients and experimental models suggests that some human variants of CoV have the ability to reach the CNS and that neurons, astrocytes and/or microglia can be target cells for CoV. A growing body of evidence shows that astrocytes and microglia have a major role in neuroinflammation, responding to local CNS inflammation and/or to dysbalanced peripheral inflammation. This is another potential mechanism for SARS-CoV-2 damage to the CNS. In this work we will summarize the known neurological manifestations of SARS-CoV-2, SARS-CoV and MERS-CoV, explore the potential role for astrocytes and microglia in the infection and neuroinflammation, and compare them with the previously described human and animal CoV that showed neurotropism. We also propose possible underlying mechanisms by focusing on our knowledge of glia, neurons, and their dynamic intricate communication with the immune system.

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Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus

Advances in Virology ◽

10.1155/2012/163860 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Otávio Valério Carvalho ◽

Clarisse Vieira Botelho ◽

Caroline Gracielle Torres Ferreira ◽

Paulo Oldemar Scherer ◽

Jamária Adriana Pinheiro Soares-Martins ◽

...

Keyword(s):

Canine Distemper Virus ◽

Clinical Manifestations ◽

Specific Treatment ◽

Viral Disease ◽

Diagnostic Methods ◽

Lymphoid Tissues ◽

Canine Distemper ◽

Worldwide Distribution ◽

Natural Hosts ◽

The Central Nervous System

Canine distemper is a highly contagious viral disease caused by the canine distemper virus (CDV), which is a member of theMorbillivirusgenus, Paramyxoviridae family. Animals that most commonly suffer from this disease belong to the Canidae family; however, the spectrum of natural hosts for CDV also includes several other families of the order Carnivora. The infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availability of effective vaccines, and no specific treatment. CDV infection in dogs is characterized by the presentation of systemic and/or neurological courses, and viral persistence in some organs, including the central nervous system (CNS) and lymphoid tissues. An elucidation of the pathogenic mechanisms involved in canine distemper disease will lead to a better understanding of the injuries and clinical manifestations caused by CDV. Ultimately, further insight about this disease will enable the improvement of diagnostic methods as well as therapeutic studies.

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Drug toxicity in the proximal tubule: new models, methods and mechanisms

Pediatric Nephrology ◽

10.1007/s00467-021-05121-9 ◽

2021 ◽

Author(s):

Andrew M. Hall ◽

Francesco Trepiccione ◽

Robert J. Unwin

Keyword(s):

Proximal Tubule ◽

Drug Toxicity ◽

Clinical Manifestations ◽

Kidney Injury ◽

In Vitro Models ◽

Cellular Mechanisms ◽

Renal Fanconi Syndrome ◽

Systemic Complications ◽

New Biomarkers

AbstractThe proximal tubule (PT) reabsorbs most of the glomerular filtrate and plays an important role in the uptake, metabolism and excretion of xenobiotics. Some therapeutic drugs are harmful to the PT, and resulting nephrotoxicity is thought to be responsible for approximately 1 in 6 of cases of children hospitalized with acute kidney injury (AKI). Clinically, PT dysfunction leads to urinary wasting of important solutes normally reabsorbed by this nephron segment, leading to systemic complications such as bone demineralization and a clinical scenario known as the renal Fanconi syndrome (RFS). While PT defects can be diagnosed using a combination of blood and urine markers, including urinary excretion of low molecular weight proteins (LMWP), standardized definitions of what constitutes clinically significant toxicity are lacking, and identifying which patients will go on to develop progressive loss of kidney function remains a major challenge. In addition, much of our understanding of cellular mechanisms of drug toxicity is still limited, partly due to the constraints of available cell and animal models. However, advances in new and more sophisticated in vitro models of the PT, along with the application of high-content analytical methods that can provide readouts more relevant to the clinical manifestations of nephrotoxicity, are beginning to extend our knowledge. Such technical progress should help in discovering new biomarkers that can better detect nephrotoxicity earlier and predict its long-term consequences, and herald a new era of more personalized medicine.

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Neurological Manifestations of Covid-19 Hospitalized Patients In the state of Punjab, India

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v20i5.55414 ◽

2021 ◽

pp. 155-161

Author(s):

Zahoor Ahmad Parry ◽

Swapnil Sunil Bumb ◽

Santosh Kumar ◽

Rohan Bhatt ◽

Mohammed Irfan ◽

...

Keyword(s):

Nervous System ◽

Medical Science ◽

Clinical Manifestations ◽

Signs And Symptoms ◽

Neurological Complications ◽

Neurological Illness ◽

Immune Mediated ◽

The Central Nervous System ◽

Neurological Presentation ◽

The Mean

Introduction: COVID 19 often presents with flu-like symptoms. Elderly patients with systemic comorbidities are more likely to have severe COVID 19 infections and deaths. Severe neurological complications are frequently reported in severely and critically ill patients. In COVID-19, both central and peripheral nervous systems can be affected. The study aims to overview the spectrum, characteristics, and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: A total of 1000 confirmed CoVID-19 patients were enrolled for the study. Demographic features and initial clinical manifestations were noted, and patients were followed during the hospital stay to develop any new neurological signs and symptoms. For analytical purposes, neurological presentations were grouped into the central nervous system, peripheral nervous system, and musculoskeletal system manifestations. Appropriate laboratory testing was employed as required on a case-to-case basis. Results: The mean age was 44.6 ± 14.3 years. 625 (62.5%) patients were male, while 375 (37.5%) were female. The neurological illness was a primary manifestation in 119 (11.9%) cases. These included encephalopathy (n=78), ischemic stroke (n=28), Guillain- Barre syndrome, (n=3), facial nerve palsy (n=4), and encephalitis (n=6). The most common neurological symptoms were headache 313 (31.3%) and hyposmia 52 (5.2%), followed by encephalopathy 78 (7.8%). More serious complications like seizures 18 (1.8%) and stroke 28 (2.8%) were also seen. Conclusion: CoVID-19 can present with a neurological illness, and we should remain vigilant to the possibility of neurological presentation of COVID-19 that can be thrombo-embolic, inflammatory, or immune-mediated. Bangladesh Journal of Medical Science Vol.20(5) 2021 p.155-161

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Neurological manifestations and complications in patients with covid-19

Translational Medicine ◽

10.18705/2311-4495-2020-7-3-21-29 ◽

2020 ◽

Vol 7 (3) ◽

pp. 21-29

Author(s):

I. K. Ternovyh ◽

M. P. Topuzova ◽

A. D. Chaykovskaya ◽

P. Sh. Isabekova ◽

T. M. Alekseeva

Keyword(s):

Nervous System ◽

Neurological Diseases ◽

Neurological Complications ◽

Epidemiological Studies ◽

Neurological Manifestations ◽

Long Time ◽

The Central Nervous System ◽

Coronavirus Infection ◽

Mechanisms Of Development ◽

Large Groups

It becomes apparent that the neurological complications of COVID-19 are significantly common, but in some cases, establishing a causal relationship is difficult. For example, a stroke can occur for reasons unrelated to coronavirus infection, while Guillain–Barré syndrome and meningoencephalitis are likely to be a parainfection. Only long-term epidemiological studies in large groups of patients can clarify some of these issues. This will help to better understand the mechanisms of development of complications and develop schemes for their treatment and subsequent rehabilitation. The article presents the mechanisms of penetration of the coronavirus into the nervous system and systematizes the neurological manifestations and complications of COVID-19, which were described in the first 3 months of the pandemic. Particular attention is paid to the consideration of the complications of COVID-19 from the central and peripheral nervous system, the most interesting clinical examples are considered. Summing up the analysis of the literature, we can say that the clinical picture of neurological diseases and syndromes caused by coronavirus infection corresponds to the usual notions. Also considered is the assumption that SARS-CoV-2 can persist for a long time in the central nervous system in the form of inactive fragments, which means that it can recur in predisposed individuals when appropriate conditions arise. This suggestion is alarming regarding distant neurological complications in infected and cured patients.

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