SARS-CoV-2 Infection Reaches the Human Nervous System: How?

Abstract

Without protective and/or therapeutic agents the SARS-CoV-2 infection known as coronavirus disease 2019 (COVID-19) is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS-CoV-2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS-CoV-2 components could use to reach the CNS and PNS, utilizing the within-body crosstalk between organs. The majority of SARS-CoV-2 infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune-mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood-endothelial-barrier may be considered as the main route for SARS-CoV-2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

Natural resources to control COVID-19: could lactoferrin amend SARS-CoV-2 infectivity?

“…Often, MDCSs are absent or redundant under steady-state physiological conditions (He et al, 2018). The body functions of patients infected with COVID-19 orchestration are disordered, and these changes exponentially increase with the patient's age (Uversky et al, 2020a). Overall, the cluster of gene expression matrixes in the leukocytes revealed that 12 and 5 clusters are dominated in COVID-19 patient and healthy control, respectively.…”

“…The virus reached almost all countries, infected humans of all ages, and even affected many animals (Uversky et al, 2020b). The virus reaches almost all human organs, including the central and peripheral nervous systems Uversky et al, 2020a), and has unexpected vertical and horizontal infectivity potential (Elrashdy et al, 2020; LF action against SARS-CoV-2, on comparison of the human and animal LFs, and on determining whether the milk whey action against SARS-CoV-2 depends on LF alone or on other milk ingredients, such as human milk oligosaccharides (HMOs) and/or short-chain fatty acids. Our report fills these gaps and produces an overview of the field, providing answers to some fundamental questions, such as why breastfed children are mostly unaffected by COVID-19 (Fan et al, 2020;Liu et al, 2021;Mitoulas, Schärer-Hernández & Liabat, 2020).…”

Neurological manifestations of coronavirus infections, before and after COVID-19: a review of animal studies

“…Besides the olfactory route (olfactory receptor neurons (OSNs) of the olfactory epithelium, olfactory bulb, and glomeruli, and their projections), which are used by neurotropic CoVs to transmit from the upper respiratory tract into the CNS, three other probable pathways have also been recognized that help these CoVs to reach the CNS from the periphery, which are as follows: (1) Neurotropic CoVs in the lower respiratory tract infect monocytes, neutrophils, lymphocytes, and macrophages of the alveoli capillaries and then spread via hematogenous transmission to get the BBB. They cross it through diapedesis and then infect neuronal and glial cells (Alquisiras-Burgos et al 2020;Uversky et al 2020); (2) Respiratory CoVs can also reach the CNS via retrograde neuronal dissemination. In fact, neurotropic CoVs firstly infect PNS, and following peripheral nerve infection, they access the CNS by axonal transport systems (Koyuncu et al 2013).…”