# Neurological consequences of COVID-19: what have we learned and where do we go from here?

**Authors:** Abbas Jarrahi, Meenakshi Ahluwalia, Hesam Khodadadi, Evila da Silva Lopes Salles, Ravindra Kolhe, David C. Hess, Fernando Vale, Manish Kumar, Babak Baban, Kumar Vaibhav, Krishnan M. Dhandapani

PMC · DOI: 10.1186/s12974-020-01957-4 · 2020-09-30

## TL;DR

This paper reviews what is known about the neurological effects of COVID-19 and suggests possible therapeutic targets to reduce these effects.

## Contribution

The paper summarizes current literature on SARS-CoV-2's impact on the central nervous system and proposes therapeutic development targets.

## Key findings

- SARS-CoV-2 can cause neurological symptoms like headaches, anosmia, and cerebral infarction.
- There is a need for controlled studies to develop therapies targeting neurological consequences of COVID-19.

## Abstract

The coronavirus disease-19 (COVID-19) pandemic is an unprecedented worldwide health crisis. COVID-19 is caused by SARS-CoV-2, a highly infectious pathogen that is genetically similar to SARS-CoV. Similar to other recent coronavirus outbreaks, including SARS and MERS, SARS-CoV-2 infected patients typically present with fever, dry cough, fatigue, and lower respiratory system dysfunction, including high rates of pneumonia and acute respiratory distress syndrome (ARDS); however, a rapidly accumulating set of clinical studies revealed atypical symptoms of COVID-19 that involve neurological signs, including headaches, anosmia, nausea, dysgeusia, damage to respiratory centers, and cerebral infarction. These unexpected findings may provide important clues regarding the pathological sequela of SARS-CoV-2 infection. Moreover, no efficacious therapies or vaccines are currently available, complicating the clinical management of COVID-19 patients and emphasizing the public health need for controlled, hypothesis-driven experimental studies to provide a framework for therapeutic development. In this mini-review, we summarize the current body of literature regarding the central nervous system (CNS) effects of SARS-CoV-2 and discuss several potential targets for therapeutic development to reduce neurological consequences in COVID-19 patients.

## Linked entities

- **Diseases:** SARS (MONDO:0005091), MERS (MONDO:0100116), pneumonia (MONDO:0005249), acute respiratory distress syndrome (MONDO:0006502), cerebral infarction (MONDO:0002679)

## Full-text entities

- **Genes:** F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, MPO (myeloperoxidase) [NCBI Gene 4353], 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}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, 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}, BTK (Bruton tyrosine kinase) [NCBI Gene 695] {aka AGMX1, AT, ATK, BPK, IGHD3, IMD1}, TMPRSS2 (transmembrane serine protease 2) [NCBI Gene 7113] {aka PRSS10}, KRT18 (keratin 18) [NCBI Gene 3875] {aka CK-18, CYK18, K18}, IL7 (interleukin 7) [NCBI Gene 3574] {aka IL-7, IMD130}, AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, SFTPC (surfactant protein C) [NCBI Gene 6440] {aka BRICD6, PSP-C, SFTP2, SMDP2, SP-C}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}
- **Diseases:** skeletal muscular injury (MESH:D014947), Critically ill (MESH:D016638), GBS (MESH:D020275), neuronal loss (MESH:D009410), cytokine storm syndrome (MESH:D000080424), SIC (MESH:D001778), nausea and vomiting (MESH:D020250), myocardial infarction (MESH:D009203), respiratory infections (MESH:D012141), CVD (MESH:D002318), neuropsychiatric adverse effects (MESH:D064420), MS (MESH:D009103), encephalitis (MESH:D004660), cerebral hypoperfusion (MESH:D002547), deaths (MESH:D003643), relapsing-remitting multiple sclerosis (MESH:D020529), hypertension (MESH:D006973), myasthenic crisis (MESH:D020294), neurological injury (MESH:D020196), confusion (MESH:D003221), cystic fibrosis (MESH:D003550), brain injury (MESH:D001930), Myasthenia gravis (MESH:D009157), respiratory system dysfunction (MESH:D015619), neurological diseases (MESH:D020271), Neurological consequences (MESH:D009461), ataxia (MESH:D001259), venous thromboembolism (MESH:D054556), ocular dysfunction (MESH:D005128), cognitive impairments (MESH:D003072), Lambert-Eaton myasthenic syndrome (MESH:D015624), nerve pain (MESH:D009437), depression (MESH:D003866), hippocampal atrophy (MESH:D001284), coma (MESH:D003128), retinopathy (MESH:D058437), NETs (MESH:C536657), venous infarction (MESH:D020520), CoV infections (MESH:D018352), cardiac/cerebrovascular disease (MESH:D006331), anxiety (MESH:D001007), platelet abnormalities (MESH:D001791), post-stroke (MESH:D020521), post-traumatic stress (MESH:D013313), agitation (MESH:D011595), Infectious encephalitis (MESH:D000069544), diarrhea (MESH:D003967), acute demyelinating encephalomyelitis (MESH:D004684), encephalopathy (MESH:D001927), respiratory failure (MESH:D012131), hemorrhagic (MESH:D006470), hypoxemia (MESH:D000860), immuno-compromised (MESH:D000163), fatigue (MESH:D005221), infected (MESH:D007239), hemorrhagic fever (MESH:D006480), obesity (MESH:D009765), tuberculosis (MESH:D014376), transverse sigmoid sinus thrombosis (MESH:D020227), fever (MESH:D005334)
- **Species:** Gammacoronavirus (genus) [taxon 694013], Human coronavirus HKU1 (no rank) [taxon 290028], Severe acute respiratory syndrome-related coronavirus (no rank) [taxon 694009], Coronaviridae (family) [taxon 11118], Middle East respiratory syndrome-related coronavirus (no rank) [taxon 1335626], Human coronavirus 229E (no rank) [taxon 11137], Mus musculus (house mouse, species) [taxon 10090], Porcine hemagglutinating encephalomyelitis virus (no rank) [taxon 42005], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Homo sapiens (human, species) [taxon 9606], Bat coronavirus (species) [taxon 1508220], Human coronavirus NL63 (no rank) [taxon 277944], Human coronavirus OC43 (no rank) [taxon 31631], Orthocoronavirinae (subfamily) [taxon 2501931]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC7525232/full.md

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Source: https://tomesphere.com/paper/PMC7525232