Potentials to alleviate coagulopathy and enhance microglial function of beta (β)- glucans, making them worth a clinical study for COVID-19's neurological sequalae

Abstract

Widespread neurological and psychiatric sequalae of COVID-19 have been reported affecting all age groups [1] with presence of low-grade chronic inflammation and down-regulated ACE-2 levels making the individual more vulnerable for severe neurological effects of COVID-19 [2] as there will be greater disruption of the blood-brain barrier and hyper inflammation. Systemic immune inflammation index (SII) including neutrophil, platelet and lymphocyte counts serve as potential biomarkers to find an individual's risk of neurological effects of . SARS-CoV2 has been shown to affect the immune pathways associated with the central nervous system (CNS) and the peripheral nervous system (PNS) leading to long-term neurological sequelae [3]. Intracranial hemorrhage, ischemic stroke, parkinsonism, dementia, anxiety disorders and psychotic disorders have been reported as sequalae of . A recently published retrospective cohort study on the neurological and psychiatric sequalae of COVID-19 in 236,379 patients [5] has shown that the incidence of ischemic stroke in about 10% of patients, majority with COVID-19 associated encephalopathy which is alarming and necessitates steps to prevent or manage in those already affected. Werner et al. [6] have reported yet another neurological sequala, incidence of transient global amnesia during the COVID-19 hypothesizing the mechanism to be an encephalitic autoimmune pathology by the SARS CoV2 virus. Neurological manifestations of COVID-19 are thus postulated to be due to the binding of SARS-CoV-2 to ACE-2 activating intracellular pattern recognition receptors (PRRs) which sense the pathogen associated molecular patterns (PAMPs) setting off maladapted immune responses leading to inflammatory and immune activities disrupting the coagulation-embolism pathways in the CNS and PNS [7]. The different types of cells in the CNS and PNS including the glial cells, neurons, endothelial and arterial smooth muscle cells are all affected leading to the neurological manifestations of . However, the effects of SARS-CoV2 on human astrocytes, especially the microglia being the key-players in neural inflammation [6] makes us specifically focus on microglia in the context of conditions that involve neural-inflammation such as stroke, Parkinson's disease, Alzheimer's etc. For recovery, optimal functioning of the neuroglia is essential for synaptic organization, neurotrophic support, phagocytosis of apoptotic cells, debris removal, myelin turnover, control of neuronal Contents lists available at ScienceDirect

ULTRASOUND-ASSISTED AND ENZYMATIC-BASED METHOD FOR ISOLATION OF Β-Glucans FROM OAT BRAN

“…-Glucan is used classically to boost the immune system and to treat hyper chole sterolemia [7,12,13,14]. For example, -glucan can modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes mellitus [15,16]. It is of interest that in the central nervous system, -glucans activate microglial cells, which act as scavengers of the brain cell debris and play a protective role in Alzheimer's disease, AIDS, ischemia injury, and multiple sclerosis [5,16,17].…”

Beta-Glucans from Fungi: Biological and Health-Promoting Potential in the COVID-19 Pandemic Era

“…Previous studies indicated the potential of β-glucans in the prevention, treatment, and complications of COVID-19 [14,169,170,[179][180][181][182][183][184][185][186][187][188][189][190][191][192]. Immunomodulatory, antioxidant, neuroprotective, and antithrombotic activities are of particular interest here.…”

Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomised, parallel-group pilot clinical study

“…In a follow-up analysis of this study, we have reported a significant decrease in Enterobacter and E. coli 25 which logically will result in lesser production of alpha-synuclein. In spite of such decreased production, the increase in plasma alpha-synuclein levels can be probably due to the disintegration of the amyloid deposits by natural killer cells leading to these alpha-synuclein entering the blood stream 26 27. These postulated mechanisms while need further in-depth research, no single intervention, or therapy has proven its ability to regulate alpha-synuclein levels, especially in children with ASD.…”

“…15 Beta-glucan has been proven to reduce the expression of inflammatory and proinflammatory markers, including Il-6 and TNF-α, 16 apart from having a neuroprotective effect by attenuating inflammatory cytokine production through microglia. 17 In another study, beta-glucan reduced induced microglia activation and its phagocytosis of synaptic puncta and upregulation of proinflammatory cytokine (TNF-α, IL-1β and IL-6) mRNA expression apart from promoting Tau signalling and improving cognition and brain function via the gutbrain axis. 18 This study was undertaken to investigate the effects of Nichi Glucan as a food supplement in children with ASD, especially with relevance to the Childhood Autism Rating Scale (CARS) score and alpha-synuclein levels.…”

“…monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6), interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) have been shown to be expressed in higher levels in children with autism 15. Beta-glucan has been proven to reduce the expression of inflammatory and proinflammatory markers, including Il-6 and TNF-α,16 apart from having a neuroprotective effect by attenuating inflammatory cytokine production through microglia 17. In another study, beta-glucan reduced induced microglia activation and its phagocytosis of synaptic puncta and upregulation of proinflammatory cytokine (TNF-α, IL-1β and IL-6) mRNA expression apart from promoting Tau signalling and improving cognition and brain function via the gut-brain axis 18…”