Abstract
The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), a respiratory pathogen with neuroinvasive potential. Neurological COVID-19 manifestations include loss of smell and taste, headache, dizziness, stroke, and potentially fatal encephalitis. Several studies found elevated proinflammatory cytokines, such as TNF-α, IFN-γ, IL-6 IL-8, IL- 10 IL-16, IL-17A, and IL-18 in severely and critically ill COVID-19 patients may persist even after apparent recovery from infection. Biomarker studies on CSF and plasma and serum from COVID-19 patients have also shown a high level of IL-6, intrathecal IgG, neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and tau protein. Emerging evidence on the matter has established the concept of COVID-19-associated neuroinflammation, in the context of COVID-19-associated cytokine storm. While the short-term implications of this condition are extensively documented, its longterm implications are yet to be understood. The association of the aforementioned cytokines with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, may increase COVID-19 patients' risk of developing neurodegenerative diseases. Analysis of proinflammatory cytokines and CSF biomarkers in patients with COVID-19 can contribute to the early detection of the disease's exacerbation, monitoring the neurological implications of the disease and devising risk scales, and identifying treatment targets.
Keywords: Cytokine storm, SARS-Coronavirus-2 infection, Neuropathological, Neuroinflammation, Neutrophil extracellular traps, ARDS
[http://dx.doi.org/10.3389/fimmu.2020.01708] [PMID: 32754163]
[http://dx.doi.org/10.1056/NEJMoa2021436] [PMID: 32678530]
[http://dx.doi.org/10.1007/s11356-021-18384-4] [PMID: 34988815]
[http://dx.doi.org/10.4103/joacp.JOACP_359_20] [PMID: 33840920]
[http://dx.doi.org/10.1016/j.dsx.2020.03.013] [PMID: 32247212]
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X] [PMID: 32085846]
[http://dx.doi.org/10.1164/rccm.202003-0817LE] [PMID: 32228035]
[http://dx.doi.org/10.1001/jamaneurol.2020.1127] [PMID: 32275288]
[http://dx.doi.org/10.1007/s00415-020-09951-9] [PMID: 32474657]
[http://dx.doi.org/10.1186/s12974-020-01957-4] [PMID: 32998763]
[http://dx.doi.org/10.3748/wjg.v27.i26.4248] [PMID: 34326624]
[http://dx.doi.org/10.1186/1743-422X-10-172] [PMID: 23724961]
[http://dx.doi.org/10.1111/j.1365-2567.2009.03225.x] [PMID: 20561356]
[http://dx.doi.org/10.1016/j.molcel.2020.04.022] [PMID: 32362314]
[http://dx.doi.org/10.1126/science.abb2762]
[http://dx.doi.org/10.1128/JVI.03368-12] [PMID: 23427150]
[http://dx.doi.org/10.1002/path.1570] [PMID: 15141377]
[http://dx.doi.org/10.1101/2020.04.07.030650]
[http://dx.doi.org/10.1073/pnas.1217508110] [PMID: 23650398]
[http://dx.doi.org/10.1159/000324777]
[http://dx.doi.org/10.1007/s42399-020-00522-7] [PMID: 33015550]
[http://dx.doi.org/10.1016/j.addr.2011.11.002] [PMID: 22119441]
[http://dx.doi.org/10.1080/13550280590922793] [PMID: 16036791]
[http://dx.doi.org/10.1016/j.bbi.2020.04.060] [PMID: 32335192]
[http://dx.doi.org/10.1016/j.psychres.2019.07.005] [PMID: 31279246]
[http://dx.doi.org/10.1016/j.msard.2020.102120] [PMID: 32315980]
[http://dx.doi.org/10.1146/annurev-immunol-042718-041417] [PMID: 31026414]
[http://dx.doi.org/10.1007/978-3-319-60189-2_8]
[http://dx.doi.org/10.1084/jem.20202135] [PMID: 33433624]
[http://dx.doi.org/10.1056/NEJMc2008597] [PMID: 32294339]
[http://dx.doi.org/10.1212/WNL.0000000000009937] [PMID: 32482845]
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104941] [PMID: 32689643]
[http://dx.doi.org/10.1016/j.omtm.2020.05.013] [PMID: 32537478]
[http://dx.doi.org/10.3389/fneur.2020.573095] [PMID: 33551947]
[http://dx.doi.org/10.1371/journal.pone.0048910] [PMID: 23155428]
[http://dx.doi.org/10.1007/s10571-020-00915-1] [PMID: 32623546]
[http://dx.doi.org/10.1183/13993003.01948-2020] [PMID: 32817004]
[http://dx.doi.org/10.1038/s41593-020-00758-5] [PMID: 33257876]
[http://dx.doi.org/10.1016/j.nbd.2020.105131] [PMID: 33053430]
[http://dx.doi.org/10.1002/jmv.25915] [PMID: 32314810]
[http://dx.doi.org/10.3390/cells9051267] [PMID: 32443810]
[http://dx.doi.org/10.3389/fimmu.2020.01949] [PMID: 32849654]
[http://dx.doi.org/10.1016/j.cell.2006.02.015] [PMID: 16497588]
[http://dx.doi.org/10.3389/fimmu.2020.01446] [PMID: 32612617]
[http://dx.doi.org/10.1097/AIA.0b013e318034194e] [PMID: 17426506]
[http://dx.doi.org/10.1186/s12974-020-01896-0] [PMID: 32758257]
[http://dx.doi.org/10.1016/j.phrs.2020.105297] [PMID: 33181319]
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[http://dx.doi.org/10.3390/ijerph18041415] [PMID: 33546463]
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[http://dx.doi.org/10.1111/j.1471-4159.2008.05723.x] [PMID: 19014390]
[http://dx.doi.org/10.1152/ajpregu.00292.2006] [PMID: 16946085]
[http://dx.doi.org/10.1152/ajpcell.00364.2012] [PMID: 23535237]
[http://dx.doi.org/10.1186/s12967-020-02571-x] [PMID: 33121497]
[http://dx.doi.org/10.3389/fimmu.2020.00827] [PMID: 32425950]
[http://dx.doi.org/10.1016/j.ijid.2020.10.003] [PMID: 33039609]
[http://dx.doi.org/10.1186/s41232-020-00146-3] [PMID: 33014208]
[http://dx.doi.org/10.2147/COPD.S164833] [PMID: 30197513]
[http://dx.doi.org/10.1038/s41598-021-82426-7] [PMID: 33536486]
[http://dx.doi.org/10.1101/cshperspect.a006148] [PMID: 22553492]
[http://dx.doi.org/10.1146/annurev-neuro-061010-113613] [PMID: 21456963]
[http://dx.doi.org/10.1523/JNEUROSCI.1808-05.2005] [PMID: 16148231]
[http://dx.doi.org/10.1007/s00415-008-0737-6] [PMID: 18204920]
[http://dx.doi.org/10.3978/j.issn.2305-5839.2015.03.49] [PMID: 26207229]
[PMID: 22026253]
[http://dx.doi.org/10.1093/jnen/59.6.471] [PMID: 10850859]
[http://dx.doi.org/10.1016/j.nlm.2018.06.006] [PMID: 29908286]
[http://dx.doi.org/10.1016/j.neuroscience.2009.08.073] [PMID: 19744544]
[http://dx.doi.org/10.1021/acschemneuro.8b00511] [PMID: 30695637]
[http://dx.doi.org/10.1007/s12603-020-1389-1] [PMID: 32510106]
[http://dx.doi.org/10.1016/j.neulet.2022.136675] [PMID: 35533819]
[http://dx.doi.org/10.1515/revneuro-2016-0002] [PMID: 26966928]
[PMID: 34897053]
[http://dx.doi.org/10.1091/mbc.e14-02-0741] [PMID: 25298402]
[http://dx.doi.org/10.1038/s41598-018-31517-z] [PMID: 30185816]
[http://dx.doi.org/10.2174/1381612053381620] [PMID: 15777250]
[http://dx.doi.org/10.1016/j.neulet.2009.10.062] [PMID: 19857551]
[http://dx.doi.org/10.1016/j.nbd.2006.06.013] [PMID: 16901708]
[http://dx.doi.org/10.1002/mds.28277] [PMID: 32815213]
[http://dx.doi.org/10.1016/S1474-4422(20)30305-7] [PMID: 32949534]
[http://dx.doi.org/10.1212/WNL.0000000000010282] [PMID: 32641525]
[http://dx.doi.org/10.1016/j.tins.2020.10.009] [PMID: 33158605]
[http://dx.doi.org/10.1038/s41531-020-00123-0] [PMID: 32885037]
[http://dx.doi.org/10.3390/brainsci6010006] [PMID: 26901230]
[http://dx.doi.org/10.3109/00365519009087509] [PMID: 2089613]
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[http://dx.doi.org/10.1021/acschemneuro.0c00181] [PMID: 32343122]
[http://dx.doi.org/10.1007/s11684-020-0786-5] [PMID: 32367431]
[http://dx.doi.org/10.1007/s12975-020-00818-9] [PMID: 32378030]
[http://dx.doi.org/10.1093/neuros/nyaa186] [PMID: 32361745]
[http://dx.doi.org/10.1016/j.jinf.2004.09.008] [PMID: 16038758]
[http://dx.doi.org/10.1111/head.13841] [PMID: 32413158]
[http://dx.doi.org/10.7759/cureus.7352] [PMID: 32328364]
[http://dx.doi.org/10.1097/PAF.0000000000000129] [PMID: 25376710]
[http://dx.doi.org/10.1016/j.cyto.2011.01.006] [PMID: 21371904]
[http://dx.doi.org/10.1111/j.1442-200X.2003.01822.x] [PMID: 14651552]
[http://dx.doi.org/10.1186/1752-1947-2-220] [PMID: 18588700]
[http://dx.doi.org/10.21203/rs.3.rs-33179/v1]
[http://dx.doi.org/10.1016/j.ijid.2020.03.062] [PMID: 32251791]
[http://dx.doi.org/10.2169/internalmedicine.45.1769] [PMID: 17139119]
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[http://dx.doi.org/10.1172/JCI137244] [PMID: 32217835]
[http://dx.doi.org/10.1016/j.jaci.2020.04.027] [PMID: 32360286]
[http://dx.doi.org/10.1093/cid/ciaa449] [PMID: 32301997]
[http://dx.doi.org/10.1007/s00134-020-05991-x] [PMID: 32125452]
[http://dx.doi.org/10.1016/j.cca.2020.03.022] [PMID: 32178975]
[http://dx.doi.org/10.2139/ssrn.3546118]
[http://dx.doi.org/10.1016/j.bbi.2020.04.046] [PMID: 32334062]
[http://dx.doi.org/10.1021/acschemneuro.0c00122] [PMID: 32167747]
[http://dx.doi.org/10.1016/j.bbi.2020.05.012] [PMID: 32387508]
[http://dx.doi.org/10.1128/JVI.00831-20] [PMID: 32404529]
[http://dx.doi.org/10.1615/CritRevImmunol.v30.i2.20] [PMID: 20370625]
[http://dx.doi.org/10.1007/s00415-020-09950-w] [PMID: 32494854]
[http://dx.doi.org/10.1016/j.neurad.2020.05.003] [PMID: 32437707]
[http://dx.doi.org/10.1089/neu.2020.7332] [PMID: 33115334]
[http://dx.doi.org/10.4103/2394-8108.178546] [PMID: 30276272]
[http://dx.doi.org/10.1111/ene.14703]
[http://dx.doi.org/10.1212/WNL.0000000000010977] [PMID: 33004602]
[http://dx.doi.org/10.3174/ajnr.A6588] [PMID: 32409316]
[http://dx.doi.org/10.1097/CCM.0b013e3181c98d21] [PMID: 20083910]
[http://dx.doi.org/10.1186/s13054-020-03077-0] [PMID: 32552865]
[http://dx.doi.org/10.1515/dx-2020-0078] [PMID: 32683333]
[http://dx.doi.org/10.1177/1076029620938149] [PMID: 32677459]
[http://dx.doi.org/10.1111/jth.14817] [PMID: 32220112]
[http://dx.doi.org/10.1007/s00134-020-06062-x] [PMID: 32367170]
[http://dx.doi.org/10.1016/j.jinf.2020.04.002] [PMID: 32283162]
[http://dx.doi.org/10.1126/sciadv.aax8847] [PMID: 32523980]
[http://dx.doi.org/10.1016/j.nmni.2020.100689] [PMID: 32355564]
[http://dx.doi.org/10.1038/35099560] [PMID: 11607032]
[http://dx.doi.org/10.4049/jimmunol.181.11.7670] [PMID: 19017955]
[http://dx.doi.org/10.1128/JVI.01410-12] [PMID: 22915814]
[http://dx.doi.org/10.1016/j.heliyon.2021.e07863] [PMID: 34458641]
[http://dx.doi.org/10.1007/s11481-020-09979-8] [PMID: 33426604]
[http://dx.doi.org/10.1007/s13365-020-00895-4] [PMID: 32839951]
[http://dx.doi.org/10.3390/brainsci10110852] [PMID: 33198412]
[http://dx.doi.org/10.1016/S2589-7500(20)30142-4] [PMID: 32835201]
[http://dx.doi.org/10.1016/j.abst.2020.08.001] [PMID: 33511330]
[http://dx.doi.org/10.1148/radiol.2020201933] [PMID: 32437313]
[http://dx.doi.org/10.1016/j.neuroimage.2018.10.003] [PMID: 30296563]
[http://dx.doi.org/10.21203/rs.3.rs-104944/v1]
[http://dx.doi.org/10.1093/cid/ciac153] [PMID: 35219277]
[http://dx.doi.org/10.1183/13993003.02523-2021] [PMID: 35115337]
[http://dx.doi.org/10.1002/alz.12556] [PMID: 35023610]
[http://dx.doi.org/10.2174/0929867033456918] [PMID: 12871095]