Review of Neurological Manifestations of SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect any part of the neuraxis. Many neurological conditions have been attributed to be caused by SARS-CoV-2, namely encephalopathy (acute necrotizing encephalopathy and encephalopathy with reversible splenial lesions), seizures, stroke, cranial nerve palsies, meningoencephalitis, acute disseminated encephalomyelitis (ADEM), transverse myelitis (long and short segment), Guillain-Barré syndrome (GBS) and its variants, polyneuritis cranialis, optic neuritis (ON), plexopathy, myasthenia gravis (MG), and myositis. The pathophysiology differs depending on the time frame of presentation. In patients with concomitant pulmonary disease, for instance, acute neurological illness appears to be caused by endotheliopathy and cytokine storm. Autoimmunity and molecular mimicry are causative for post-coronavirus disease 2019 (COVID-19)-sequelae. It has not yet been shown that the virus can penetrate the central nervous system (CNS) directly. This review aims to describe the disease and root pathogenic cause of the various neurological manifestations of COVID-19. We searched Pubmed/Medline and Google Scholar using the keywords “SARS-CoV-2” and “neurological illness” for articles published between January 2020 and November 2022. Then, we used the SWIFT-Review (Sciome LLC, North Carolina, United States), a text-mining workbench for systematic review, to classify the 1383 articles into MeSH hierarchical tree codes for articles on various parts of the nervous system, such as the CNS, peripheral nervous system, autonomic nervous system, neuromuscular junction, sensory system, and musculoskeletal system. Finally, we reviewed 152 articles in full text. SARS-CoV-2 RNA has been found in multiple brain areas without any histopathological changes. Despite the absence of in vivo virions or virus-infected cells, CNS inflammation has been reported, especially in the olfactory bulb and brain stem. SARS-CoV-2 genomes and proteins have been found in affected individuals’ brain tissues, but corresponding neuropathologic changes are seldom found in these cases. Additionally, viral RNA can rarely be identified in neurological patients’ CSF post hoc SARS-CoV-2 infection. Most patients with neurological symptoms do not have active viral replication in the nervous system and infrequently have typical clinical and laboratory characteristics of viral CNS infections. Endotheliopathy and the systemic inflammatory response to SARS-CoV-2 infection play a crucial role in developing neuro-COVID-19, with proinflammatory cytokine release mediating both pathological pathways. The systemic inflammatory mediators likely activate astrocytes and microglia across the blood-brain barrier, indirectly affecting CNS-specific immune activation and tissue injury. The management differs according to co-morbidities and the neurological disorder.

Inflammatory Response and Defects on Myelin Integrity in the Olfactory System of K18hACE2 Mice Infected with SARS-CoV-2

“…SARS-CoV-2 is characterized in part by the rapid infection of cells in the nasal cavity. The virus easily spreads into the lungs and other organs, causing severe inflammatory reactions and tissue damage (Brodin, 2021;Lamers and Haagmans, 2022;Merad et al, 2022;Priyal et al, 2023). The nasal cavity mucosa is covered by two epithelia.…”

“…As COVID-19 progresses, a variety of neurological symptoms develop in up to 45% of patients (Priyal et al, 2023), suggesting that SARS-CoV-2 perturbs neuronal function. However, although the neuroinvasive potential of SARS-CoV-2 was proposed at the outset of the pandemic (Li et al, 2020;Mao et al, 2020;Moriguchi et al, 2020;Varatharaj et al, 2020), solid evidence to demonstrate neuronal infection in human tissue remains in dispute.…”

Postacute Sequelae SARS-CoV-2 Infection by Vaccination Status: A Six-Month Latent Class Analysis

“…Although data are still limited regarding the underlying pathophysiology of PASC (Nalbandian et al 2021), understanding the patient symptomatology and care needs after the acute stages of SARS-CoV-2 infection can lead to potential interventions addressing PASC. Furthermore, there are a paucity of data in identifying clusters of symptoms associated with PASC (Natarajan et al 2023, Priyal et al 2023, Thaweethai et al 2023, Yugar-Toledo et al 2023.…”