IS COVID-19 HURTING YOUR BRAIN?
UNREVEALING THE BATTLE BETWEEN VIRUS & YOUR BRAIN
INTRODUCTION:
As the COVID-19 pandemic rocketed around the globe, it quickly became clear that this was not your average respiratory illness, can also lead to neurological problems. The disease appears to affect a number of body systems, including the heart and the brain. Early on in the pandemic, there came reports that many people with the disease had lost their sense of smell, while some people also may later battle headaches, debilitating fatigue, and trouble thinking clearly, sometimes referred to as “brain fog.” a curious symptom suggesting the virus may affect the nervous system. As more people became infected with moderate and severe COVID-19 experience a range of neurological, cognitive, psychological and psychiatric symptoms SARS-CoV-2 might cross the blood-brain barrier and invade the brain. Indeed, a recent report by NIH-funded researchers showed that the viral spike protein, when injected into mice, readily entered the brain along with many other organs. MRS can identify neurochemical abnormalities even when structural imaging findings are normal. COVID-19 patients’ brains showed N-acetyl-aspartate (NAA) reduction, choline elevation, and myo-inositol elevation, similar to what is seen with these metabolites in other patients with white matter abnormalities (leukoencephalopathy) after hypoxia without COVID.COVID-19 patients also showed the most severe white matter damage (necrosis and cavitation) had particularly pronounced lactate elevation on MRS, which is another sign of brain damage from oxygen deprivation.
VIRUS -BRAIN INTERACTION:
I-S1 was taken up by all 11 brain regions examined. S1 protein (encoded by mRNA) is the SARS-CoV-2 protein that initially binds to cell-surface receptors, setting the stage for viral internalization. Additionally, many viral proteins themselves can be biologically highly active; for example, gp120 is highly toxic. Coronavirus spike proteins are often cleaved from the virus by host cell proteases. Once cleaved, coronavirus spike S1 and S2 subunits are not held covalently by disulfide bonds and so S1 could be shed from virions. It is possible that during infection by SARS-CoV-2, shed S1 is available to cross the BBB, triggering inflammation and subsequent neurotoxicity responses in the brain.
COVID-19 HITS BRAIN: PRESPECTIVE OF NEUROLOGICAL INVOLVEMENT IN COVID-19:
INTRODUCTION:
Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain–Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic. Even though COVID-19 respiratory infections and cardiovascular events are the leading cause of mortality, clinical awareness of physicians about neurological accidents, reduce the mortality rate in infected individuals. Future investigations on the determination of the specific risk factors or protective determinants concerning neurological events are needed to diminish the risk of these complications in COVID-19 infection. It directly and indirectly affects the care of neurological diseases. SARS-CoV-2 infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases.
HOW COVID-19 DAMAGES THE BRAIN:
Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis.
Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury.
Coronavirus can be neuroinvasive and cause direct CNS infection; this was convincingly demonstrated by the detection of particles and/or RNA of SARS-CoV-1, a virus with 79% genetic homology to SARS-CoV-2. There was an active viral entry across the brain microvasculature into the neurons, as there was blebbing of viral particles coming in and out of the endothelial membrane. Mechanistically, SARS-CoV-2 virus may enter the CNS through hematogenous route or retrograde synaptic transmission. The ACE 2 protein, which functions as a receptor for SARS-CoV-2, is abundantly expressed in the endothelial cells, supporting glia and neurons, and might be the binding site facilitating hematogenous entry.
The systemic hyper-inflammation increases the permeability of the blood–brain and blood-CSF barriers, which might facilitate CNS entry, as well. Retrograde synaptic transmission may occur via the olfactory nerves. This possibility is supported by the fact that anosmia is a frequent early sign of COVID-19 . It has been proposed that SARS-CoV-2 neurotropism may explain not only the common symptoms of encephalitis, but also the respiratory failure, by involvement of the medullary respiratory centers.
MECHANISMS OF SARS-CoV-2 TRANSMISSION & PATHOGENESIS:
Ø DIRECT PATHWAY
1. NEURAL PATHWAY:
§ Entry of virus via nose
§ SARS-CoV-2 might access the brain through the olfactory mucosa.
2. HAEMATOGENOUS PATHWAY:
§ The virus in peripheral circulation might reach the brain via cerebral circulation.
§ The blood flow in the cerebral microvasculature, is responsible for the binding between the ACE2 of capillary endothelium with viral spike proteins, allowing the viral particle to be transported across the BBB.
§ Involvement of the Brain Barriers in CNS Infection.
Ø INDIRECT PATHWAY
1. HYPOXIC INJURY:
Hypoxic brain damage occur in severe COVID-19 patients. Acute hypoxemia may result in hypoxic ischemic encephalopathy. Prolonged hypoxia may induce demyelination or produce white matter microhemorrhages. Prolonged hypoxemia leads to oligodendroglial cell injury.
2. IMMUNE INJURY:
CoV-2 infection of CNS activates CD4+ cells of the immune system, which induces the macrophage to secrete interleukin-6 (IL-6) by producing granulocyte-macrophage colony-stimulating factor.
3. HYPERCOAGULABILITY:
Coagulation dysfunction, increasingly reported in severe COVID-19 may precipitate large vessel strokes, dural venous thrombosis, or intracranial hemorrhage.
4. VASCULAR INJURY:
Vascular injury may result from tropism of SARS-CoV-2 for endothelial cells which express ACE2, the target receptor for SARS-CoV-2, may cause cerebral vascular thrombosis or may lead to disruption of BBB.
COMPLICATIONS DUE TO COVID-19 AMONG PATIENTS ALREADY HAVE SOME NEUROLOGICAL DISEASE
1. COVID-19 CMPLICATIONS IN PARKINSON’S DISEASE
Recent study by Antonini et al., in a PD patients of older age with longer disease duration were particularly susceptible to COVID-19 with a substantially high mortality rate. In cohort study, PD patients experienced substantial worsening of both motor and non-motor symptoms (especially urinary issues and fatigue), during mild-to-moderate COVID-19 illness independently of age and duration. Shalash et al. investigated the impact of the COVID-19 pandemic on the mental health, physical activities, and quality of life of PD patients. Compared with controls, PD patients complained a negative impact on their mental health, physical activity and health care. Clinical deterioration observed in PD patients by both infection-related mechanisms and impaired pharmacokinetics of dopaminergic therapy.
2. COV-2 COMPLICATIONS IN MULTIPLE SCLEROSIS
The CoV family has been potentially associated with MS. It has further been complex the challenge the risk of the viral infection in MS patients, especially those receiving immunosuppressant or immunomodulatory therapy. Although it has been documented that MS patients may have an increased risk of the infections compared with the general population. Another study aimed to examine the risk of serious infections associated with used MS DMTs as well as rituimab, which is commonly used in this population. MS patients treated with DMTs are at a generally increased risk of infections.
3. COVID-19 COMPLICATIONS IN ALZHEIMER’S DISEASE
AD patients are vulnerable to disasters and crisis such as CoV-19 pandemic, because of their neurocognitive impairments and neuropsychiatric symptomatology. About the 80% of AD patients may exhibit at least one neuropsychiatric symptom. AD clinical spectrum, neuropsychiatric symptoms including depression, anxiety, agitation, and hallucinations appear to be subjected to a sudden deterioration. Moreover, it should also be considered the consequences of these features increased rate of disease progression and institutionalization; alteration of the treatment responses and prognosis; decrease of the patient’s quality of life. These studies shows the worsening of clinical spectrum, especially neuropsychiatric symptoms during CoV-19 pandemic in AD patients.
PANDAMIC AND MENTAL BURNOUT?
NEUROPSYCHOLOGICAL SEQUELAE OF COVID-19
INTRODUCTION:
As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak.
PSYCHOLOGICAL ALTERATION IN PATIENTS SUFFERED FROM COVID-19 INFECTION
Through the common mechanisms, both SARS-CoV-2 infection & social isolation can lead to mental health impairments, hematogenic or neuronal routes (via olfactory nerve) may be involved in the entry of the SARS-CoV-2 into the central nervous system. In the CNS, the virus can lead to increase in cytokines levels (e.g., IL-2, IL-6, TNF-α, IL-1β, INF-γ, & IL-10) due to its local or peripheral actions. Increased cytokine levels are associated to neuronal death, synaptic plasticity impairments, dysfunction in the neurotransmitter metabolism and in the hypothalamic-pituitary-adrenocortical (HPA) axis. Social isolation can also lead to these neuroendocrine-immune disturbances, for instance: increase in cytokine levels, changes in neurotransmitter systems, HPA axis hyperactivity and disturbances in neuroplasticity-related signaling pathways.
NEUROPSYCHOLOGY IMPACT of PANDAMIC / LOCKDOWN IN NORMAL HEALTHY POPULATION
This unprecedented situation related to COVID-19 outbreak is clearly demonstrating that individuals are largely and emotionally unprepared to the detrimental effects of biological disasters that are directly showing how everyone may be frail and helpless. Social distancing and important lockdown restrictions have been carried out first in China and later in most European countries where Italy and Spain experienced a tragic growth of the number of positive cases. Although government regulations are necessary to maintain social balance and guarantee the safety of all individuals, a direct strategy aimed to manage the psychosocial issues related to COVID-19 crisis and its consequences in the community is currently lacking
MENTAL ILLNESS DUE TO PANDEMIC IN NORMAL HEALTHY POPULATION
1. RUMINATION
General tendency to worry and “ruminate” on negative thoughts from your inner voice. PMHW studies and others suggest this arises when the brain’s default mode circuit is in overdrive, making calmer self-reflection difficult.
2. ANHEDONIA
Unable to take pleasure in activities that usually bring you joy, associated with reduced activation in the brain’s positive affect circuits that previously responded to rewarding events, activities and memories.
3. NEGATIVE BIAS
A tendency to dwell on the negative aspects of your experience associated with the over-activation of the brain’s negative affect circuit that, when functioning optimally, helps us detect risk and appraise negative emotion but does not generate negative biases.
4. INATTENTION
Difficulty concentrating and staying focused associated with disruptions in the connectivity of the brain’s attention circuit.
5. THREAT RESPONSE
Automatic reactions that are activated when the brain’s negative affect circuit is put into “alarm mode” by threatening situations (real or perceived, immediate or remembered, physical and social) and which are hard to switch off when the sense of threat persists.
6. COGNITIVE FOG
Brain may feel foggy, reflecting reduced activation in the cognitive control circuit (the brains “executive”).
COVID PATIENTS AND MENTAL HEALTH:
People with depressive, anxiety, or obsessive-compulsive disorders are experiencing a detrimental impact on their mental health from the COVID-19 pandemic, which requires close monitoring in clinical practice. Yet, the COVID-19 pandemic does not seem to have further increased symptom severity compared with their pre-pandemic levels. Outcomes of the COVID-19 pandemic on mental health could differ between population groups. In particular, the emotional responses brought on by the pandemic and its management might be more substantial among vulnerable groups, such as people with pre-existing psychiatric conditions. Financial instability and small social networks are common among people with mental illness; as a result of economic recession and restricted social connectivity, the COVID-19 pandemic could present an unprecedented stressor to these individuals.9 Measures such as nationwide travel restrictions and quarantine, and changes in the way health-care services are provided, could interrupt access to and provision of psychiatric care.
COMPLICATIONS DUE TO COVID-19 AMONG PATIENTS ALREADY HAVE SOME NEUROLOGICAL DISEASE
1. IMPACT OF THE CORONAVIRUS ON PEOPLE WITH BIPOLAR DISORDER
Potentially higher risk of coronavirus exposure and infection in patients with bipolar disorder. Bipolar disorder are associated with cognitive deficits, including executive dysfunction. In addition, people with bipolar disorder comprise a disenfranchised group, with lower educational attainment and health literacy, on average, compared to the general population. Such factors may make it harder for people with bipolar to find accurate information about COVID-19 and to organize, appraise, and translate health information into behavior that reduces risk of exposure and infection. Some studies suggest that a number of patients with bipolar disorder may lack the basic necessity of a safe and secure location in which to practice social distancing. In recent study, in New York, people with disabilities living in group homes were found to be 5.3 times more likely than the general population to develop COVID-19 and 4.9 times more likely to die from it.
2. IMPACT OF THE CORONAVIRUS ON PEOPLE WITH SCHIZOPHRENIA
Negative health-related behaviors may also increase infection risk in schizophrenia patients. Some studies suggest that SMI patients may have lower rates of adherence to treatment for medical conditions. Thus, it is possible that patients, especially those who are more acutely ill, may have a harder time complying with protective hygiene measures, stay-at-home orders, and other health guidance during this pandemic. Individuals with schizophrenia face greater risk of coronavirus exposure and infection because of structural barriers that can hinder their ability to successfully quarantine at home. Patients is associated with higher rates of homelessness and unstable housing. Furthermore, for patients residing in communal settings, such as shelters, psychiatric units, and group homes, there can be heightened risk of contagion, as occurred in South Korea, where 101 of 103 patients in a psychiatric unit contracted COVID-19 and 7 died.
3. IMPACT OF THE CORONAVIRUS ON PEOPLE WITH MOOD disorder
Physical-distancing strategies during the coronavirus (COVID-19) pandemic may be particularly detrimental to the mental health of individuals with a pre-existing mood disorder. Greater risk of coronavirus exposure and infection in patients with mood disorder. Psychological distress was heightened in the mood disorder group compared to the group with no mental disorder, with stress and depression further elevated in respondents with bipolar disorder compared to those with depressive disorder; and men with mood disorder having even higher levels of depression than women with mood disorder.. Adverse changes to lifestyle behaviors were more prevalent in respondents with a mood disorder and linked to higher levels of distress.
By: Dania Rehman Ansari
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