SARS-CoV-2 and nervous system: From pathogenesis to clinical manifestation

Abstract

Since the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a growing body of evidence indicates that besides common COVID-19 symptoms, patients may develop various neurological manifestations affecting both the central and peripheral nervous systems as well as skeletal muscles. These manifestations can occur prior, during and even after the onset of COVID-19 general symptoms. In this Review, we discuss the possible neuroimmunological mechanisms underlying the nervous system and skeletal muscle involvement, and viral triggered neuroimmunological conditions associated with SARS-CoV-2, as well as therapeutic approaches that have been considered for these specific complications worldwide.

Keywords: Coronavirus disease 2019 (COVID-19); Encephalitis; Guillain-Barré syndromes; Myelitis; Neuroimmunity; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Fig. 1

A schematic neural network and synaptic space as well as pathways for intracellular SARS-CoV-2 cycle and its effect on both innate and advance immune response. (A) Neural network and main 3 parts of a neuron (cell body, dendritic branches and axon); (B) Synaptic space and transmission of neurotransmitters and SARS-CoV-2 viruses in similar manner; and (C) Pathways for viral fusion, viral RNA replication and assembly and finally excretion in any cell type including neurons. Virus enter the cell via endocytosis and then are lysed to their protein particles and nucleic acid through endosomal acidification. Viral genome is both replicated and translated to have all parts needed for reassembly of virions and excretion. RNA is replicated by help of RNA-dependent RNA polymerase (RdRP) and replication complex, which is made up from viral protein particles and viral replicase polyprotein. There are different medications blocking each step of the cascade which are outlined in red. (D) Depiction of the mechanisms of viral effects on both innate and advance immune response. There is an interplay between all immune cells types which leads to rapid increase in pro-inflammatory cytokine release and cytokine storm. As the initial immune response neutrophil number raise and macrophages as antigen presenting cells activate T helper and T cytotoxic cells via MHC class II and I respectively. T helper cells also help activating B cells and T cytotoxic cells. All these activated cells secrete pro-inflammatory cytokines including IL-6 and TNF-α. GMCSF, granulocyte-macrophage colony stimulating factor; TMPRSS2, transmembrane protease, serine 2. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)