Tangled quest of post-COVID-19 infection-caused neuropathology and what 3P nano-bio-medicine can solve?

Abstract

COVID-19-caused neurological problems are the important post-CoV-2 infection complications, which are recorded in ~ 40% of critically ill COVID-19 patients. Neurodegeneration (ND) is one of the most serious complications. It is necessary to understand its molecular mechanism(s), define research gaps to direct research to, hopefully, design new treatment modalities, for predictive diagnosis, patient stratification, targeted prevention, prognostic assessment, and personalized medical services for this type of complication. Individualized nano-bio-medicine combines nano-medicine (NM) with clinical and molecular biomarkers based on omics data to improve during- and post-illness management or post-infection prognosis, in addition to personalized dosage profiling and drug selection for maximum treatment efficacy, safety with least side-effects. This review will enumerate proteins, receptors, and enzymes involved in CoV-2 entrance into the central nervous system (CNS) via the blood–brain barrier (BBB), and list the repercussions after that entry, ranging from neuroinflammation to neurological symptoms disruption mechanism. Moreover, molecular mechanisms that mediate the host effect or viral detrimental effect on the host are discussed here, including autophagy, non-coding RNAs, inflammasome, and other molecular mechanisms of CoV-2 infection neuro-affection that are defined here as hallmarks of neuropathology related to COVID-19 infection. Thus, a couple of questions are raised; for example, “What are the hallmarks of neurodegeneration during COVID-19 infection?” and “Are epigenetics promising solution against post-COVID-19 neurodegeneration?” In addition, nano-formulas might be a better novel treatment for COVID-19 neurological complications, which raises one more question, “What are the challenges of nano-bio-based nanocarriers pre- or post-COVID-19 infection?” especially in the light of omics-based changes/challenges, research, and clinical practice in the framework of predictive preventive personalized medicine (PPPM / 3P medicine).

Extracellular Vesicles: The Invisible Heroes and Villains of COVID‐19 Central Neuropathology

“…It is undeniable that the field of EVs in the pathology, prediction, diagnosis, and treatment of COVID‐19‐related neurological complications requires further attention, effort, and extensive preclinical data and evaluation with larger patient cohorts before the clinical application can be considered. [ 9b ]…”

“…EVs refers to a heterogeneous group of membranous vesicles, including exosomes, microvesicles, microparticles, tumor bodies, and prostatic bodies, with sizes ranging from 20 to 500 nm. [ 9 , 51 ] These membranous organelles can be released by cells from all three domains of life—Archaea, Bacteria, and Eukarya. [ 52 ] In addition, EVs contain a diverse array of molecules, such as proteins, lipids, DNA, mRNAs, microRNAs (miRNAs), circular RNAs (circRNAs), long non‐coding RNAs (lncRNAs), and pathogen‐derived nucleic acids.…”

“…[ 8 ] However, the exact mechanism remains incomplete, and the relationship between SARS‐CoV‐2 and neurological deterioration has not yet been established. [ 9 ]…”

“…[ 13 ] Substantial evidence suggests that the neuropathological characteristics of COVID‐19 arise primarily from two mechanisms: direct virus invasion, via a “Trojan horse” mechanism whereby the virus enters the brain through neural pathways or circulation [ 14 ] and systemic deteriorations induced by respiratory diseases, such as inflammation and coagulation dysfunction. [ 9 , 15 ] EVs have been implicated in the pathogenesis of COVID‐19, participating in viral infections, inflammatory storms, thrombosis, and more. [ 16 ] Additionally, EVs’ involvement in virus‐related cognitive dysfunctions, such as HIV‐associated neurological disorders (HANDs), is well‐established.…”

Iron oxide nanoparticles: a narrative review of in-depth analysis from neuroprotection to neurodegeneration

“…The olfactory neural pathway enters the brain via two distinct routes: the extra-neuronal pathway and the intraneuronal pathway. 24 Axonal transport constitutes the intra-neuronal route that enables active compounds to reach the brain, and it might take from a few hours to days. Active molecules can reach the brain in just a few minutes when the transportation route involves perineural channels.…”