# Neurological Aspects of SARS-CoV-2 Infection: Mechanisms and Manifestations

**Authors:** Parménides Guadarrama-Ortiz, José Alberto Choreño-Parra, Claudia Marisol Sánchez-Martínez, Francisco Javier Pacheco-Sánchez, Alberto Iván Rodríguez-Nava, Gabriela García-Quintero

PMC · DOI: 10.3389/fneur.2020.01039 · Frontiers in Neurology · 2020-09-04

## TL;DR

This paper reviews how SARS-CoV-2 can affect the nervous system, exploring neurological symptoms and their underlying mechanisms.

## Contribution

The paper provides a comprehensive review of neurological manifestations and mechanisms of SARS-CoV-2 infection.

## Key findings

- SARS-CoV-2 can cause neurological symptoms like peripheral neuropathy and meningoencephalitis.
- The virus may use specific host and pathogen factors to invade the nervous system.
- Neurological complications of SARS-CoV-2 are supported by evidence from clinical and pathological studies.

## Abstract

The human infection of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern that has caused more than 16.8 million new cases and 662,000 deaths as of July 30, 2020. Although coronavirus disease 2019 (COVID-19), which is associated with this virus, mainly affects the lungs, recent evidence from clinical and pathological studies indicates that this pathogen has a broad infective ability to spread to extrapulmonary tissues, causing multiorgan failure in severely ill patients. In this regard, there is increasing preoccupation with the neuroinvasive potential of SARS-CoV-2 due to the observation of neurological manifestations in COVID-19 patients. This concern is also supported by the neurotropism previously documented in other human coronaviruses, including the 2002–2003 SARS-CoV-1 outbreak. Hence, in the current review article, we aimed to summarize the spectrum of neurological findings associated with COVID-19, which include signs of peripheral neuropathy, myopathy, olfactory dysfunction, meningoencephalitis, Guillain-Barré syndrome, and neuropsychiatric disorders. Furthermore, we analyze the mechanisms underlying such neurological sequela and discuss possible therapeutics for patients with neurological findings associated with COVID-19. Finally, we describe the host- and pathogen-specific factors that determine the tissue tropism of SARS-CoV-2 and possible routes employed by the virus to invade the nervous system from a pathophysiological and molecular perspective. In this manner, the current manuscript contributes to increasing the current understanding of the neurological aspects of COVID-19 and the impact of the current pandemic on the neurology field.

## Linked entities

- **Diseases:** coronavirus disease 2019 (MONDO:0100096), Guillain-Barré syndrome (MONDO:0016218), meningoencephalitis (MONDO:0005845), peripheral neuropathy (MONDO:0003620)

## Full-text entities

- **Genes:** TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, S (surface glycoprotein) [NCBI Gene 43740568] {aka spike glycoprotein}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, FURIN (furin, paired basic amino acid cleaving enzyme) [NCBI Gene 5045] {aka FUR, PACE, PCSK3, SPC1}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PIKFYVE (phosphoinositide kinase, FYVE-type zinc finger containing) [NCBI Gene 200576] {aka FAB1, HEL37, PIP5K, PIP5K3, ZFYVE29}, TMPRSS2 (transmembrane serine protease 2) [NCBI Gene 7113] {aka PRSS10}, SHH (sonic hedgehog signaling molecule) [NCBI Gene 6469] {aka HHG1, HLP3, HPE3, MCOPCB5, SMMCI, ShhNC}, Ctsl (cathepsin L) [NCBI Gene 13039] {aka 1190035F06Rik, CatL, Ctsl1, MEP, fs, nkt}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, TICAM1 (TIR domain containing adaptor molecule 1) [NCBI Gene 148022] {aka IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Tmprss2 (transmembrane protease, serine 2) [NCBI Gene 50528] {aka D16Ertd61e}, KITLG (KIT ligand) [NCBI Gene 4254] {aka DCUA, DFNA69, FPH2, FPHH, KL-1, Kitl}, CTSL (cathepsin L) [NCBI Gene 1514] {aka CATL, CTSL1, MEP}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, TMPRSS4 (transmembrane serine protease 4) [NCBI Gene 56649] {aka CAP2, CAPH2, MT-SP2, TMPRSS3}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}
- **Diseases:** migraine (MESH:D008881), Autoimmune Neurological Syndromes (MESH:D020274), CNS infection (MESH:D002494), schizophrenia (MESH:D012559), neck (MESH:D006258), hyposmia (MESH:D000086582), cough (MESH:D003371), inflammatory (MESH:D007249), ischemic (MESH:D002545), multiorgan failure (MESH:D051437), lymphopenia (MESH:D008231), Meningitis (MESH:D008580), delirium (MESH:D003693), paralysis of the eye muscles (MESH:D012133), Dizziness (MESH:D004244), myalgia (MESH:D063806), anosmia (MESH:D000857), lethargy (MESH:D053609), thrombotic microangiopathy (MESH:D057049), neurological complication (MESH:D002493), thrombotic (MESH:D013927), infectious diseases (MESH:D003141), Seizures (MESH:D012640), flu (MESH:D007251), symptoms (MESH:D012816), polyneuropathy (MESH:D011115), brain embolization (MESH:D020766), neurotoxic (MESH:D020258), muscle weakness (MESH:D018908), respiratory symptom (MESH:D012818), complications (MESH:D008107), leukopenia (MESH:D007970), hematological malignancies (MESH:D019337), sepsis (MESH:D018805), disorganized thinking (MESH:D012562), viral infection (MESH:D014777), insomnia (MESH:D007319), manifestations (MESH:D012877), cerebral infarctions (MESH:D002544), Cerebrovascular Disease (MESH:D002561), COVID-19 (MESH:D000086382), opacities (MESH:D003318), pneumonia (MESH:D011014), facial palsy (MESH:D005158), areflexia (MESH:D000071699), respiratory diseases (MESH:D012140), demyelinating neuropathy (MESH:D003711), viral encephalitis (MESH:D018792), neuropsychiatric disorders (MESH:D001523), myocarditis (MESH:D009205), thrombocytopenia (MESH:D013921), ophthalmoplegia (MESH:D009886), acute respiratory distress syndrome (MESH:D012128), memory impairment (MESH:D008569), psychosis (MESH:D011618), Loss of consciousness (MESH:D014474), DIC (MESH:D004211), meningoencephalitis (MESH:D008590), tension-type (MESH:D018781), febrile illness (MESH:D005334)
- **Species:** Campylobacter jejuni (species) [taxon 197], Human coronavirus NL63 (no rank) [taxon 277944], Human coronavirus OC43 (no rank) [taxon 31631], Orthocoronavirinae (subfamily) [taxon 2501931], Betacoronavirus (genus) [taxon 694002], Zika virus (no rank) [taxon 64320], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Chiroptera (bats, order) [taxon 9397], Human immunodeficiency virus 1 (no rank) [taxon 11676], Middle East respiratory syndrome-related coronavirus (no rank) [taxon 1335626], Bacillus sp. AT (species) [taxon 1196779], Human coronavirus 229E (no rank) [taxon 11137], Mus musculus (house mouse, species) [taxon 10090], Mycoplasmoides pneumoniae (Filterable agent of primary atypical pneumonia, species) [taxon 2104], Gammacoronavirus (genus) [taxon 694013], Porcine coronavirus (species) [taxon 2978516], Human coronavirus HKU1 (no rank) [taxon 290028], Severe acute respiratory syndrome-related coronavirus (no rank) [taxon 694009], Influenza A virus (no rank) [taxon 11320], Human alphaherpesvirus 3 (Varicella-zoster virus, no rank) [taxon 10335]
- **Cell lines:** CAR-T — Mus musculus (Mouse), Transformed cell line (CVCL_WN86), hACE2 — Homo sapiens (Human), Transformed cell line (CVCL_C1G1), 293 — Homo sapiens (Human), Transformed cell line (CVCL_0045)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC7499054/full.md

## References

130 references — full list in the complete paper: https://tomesphere.com/paper/PMC7499054/full.md

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Source: https://tomesphere.com/paper/PMC7499054