{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T07:27:01Z","timestamp":1776929221349,"version":"3.51.2"},"reference-count":60,"publisher":"IMR Press","issue":"11","license":[{"start":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T00:00:00Z","timestamp":1669766400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2019R1A2C2002166812"],"award-info":[{"award-number":["2019R1A2C2002166812"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: The recently emerged variants of the severe acute respiratory coronavirus 2 (SARS-CoV-2) pose a threat to public health. Understanding the pathogenicity of these variants is a salient factor in the development of effective SARS-CoV-2 therapeutics. This study aimed to compare the expression patterns of genes involved in immune responses in K18-hACE2 mice infected with the wild-type, Delta, and Omicron SARS-CoV-2 variants. Methods: K18-hACE2 mice were intranasally infected with either wild-type (B.1), Delta (B.1.617.2), or Omicron (B.1.1.529) variants. On day 6 post-infection, lung, brain, and kidney tissues were collected from each variant-infected group. The mRNA expression levels of 39 immune response genes in all three groups were compared by RT-qPCR. Viral titers were measured using the median tissue culture infectious dose (TCID50) assay and expressed as Log10 TCID50\/0.1 g. The statistical significance of the differences in gene expression was determined by one-way analysis of variance (ANOVA) (alpha = 0.05). Results: The expression of toll-like receptors (TLRs) was upregulated in the lung and brain tissues of the wild-type- and Delta-infected groups but not in those of the Omicron-infected group. The highest expression of cytokines, including interleukin (IL)-1\u03b1, IL-1\u03b2, IL-17\u03b1, interferon, and tumor necrosis factors, was observed in the lungs of mice infected with the wild-type variant. Additionally, CCL4, CCL11, CXCL9, and CXCL10 were upregulated (&gt;3-fold) in wild-type-infected mice, with markedly higher expressions in the brain than in the lungs. Most of the apoptotic factors were mainly expressed in the brain tissues of Omicron-infected mice (caspase 8, caspase 9, p53, Bax, Bak, BCL-2, and Bcl-XL), whereas neither the lung nor kidney showed more than 3-fold upregulation of these apoptotic factors. Conclusions: Collectively, our findings revealed that the wild-type SARS-CoV-2 variant exhibited the highest pathogenicity, followed by the Delta variant, then the Omicron variant.<\/jats:p>","DOI":"10.31083\/j.fbl2711316","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T07:27:57Z","timestamp":1669793277000},"source":"Crossref","is-referenced-by-count":16,"title":["Comparison of the Pathogenicity of SARS-CoV-2 Delta and Omicron Variants by Analyzing the Expression Patterns of Immune Response Genes in K18-hACE2 Transgenic Mice"],"prefix":"10.31083","volume":"27","author":[{"given":"Kuruppu Arachchillage Praboda Priyangi","family":"Kuruppuarachchi","sequence":"first","affiliation":[{"name":"Laboratory of Influenza Research, College of Veterinary Medicine, Chungnam National University, 34134 Daejeon, Republic of Korea"},{"name":"Institute of Influenza Virus, Chungnam National University, 34134 Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunyueng","family":"Jang","sequence":"first","affiliation":[{"name":"Laboratory of Influenza Research, College of Veterinary Medicine, Chungnam National University, 34134 Daejeon, Republic of Korea"},{"name":"Institute of Influenza Virus, Chungnam National University, 34134 Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Heui","family":"Seo","sequence":"first","affiliation":[{"name":"Laboratory of Influenza Research, College of Veterinary Medicine, Chungnam National University, 34134 Daejeon, Republic of Korea"},{"name":"Institute of Influenza Virus, Chungnam National University, 34134 Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Hasoksuz M, Kilic S, Sarac F. Coronaviruses and SARS-COV-2. Turkish Journal of Medical Sciences. 2020; 50: 549\u2013556.","DOI":"10.3906\/sag-2004-127"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Allen H, Tessier E, Turner C, Anderson C, Blomquist P, Simons D, et al. Comparative Transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) Variants and the Impact of Vaccination: National Cohort Study. England. 2022. (preprint)","DOI":"10.1017\/S0950268823000420"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Liu Z, Xiao X, Wei X, Li J, Yang J, Tan H, et al. Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS\u2010CoV\u20102. Journal of Medical Virology. 2020; 92: 595\u2013601.","DOI":"10.1002\/jmv.25726"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Lvov DK, Alkhovsky SV. Source of COVID-19 Pandemic: Ecology and Genetics of Coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (Subgenus Sarbecovirus), and MERS-CoV (Subgenus Merbecovirus). Problems of Virology. 2020; 65: 62\u201370.","DOI":"10.36233\/0507-4088-2020-65-2-62-70"},{"key":"ref5","unstructured":"World Health Organization. Tracking SARS-CoV-2 Variants. 2022. Available at: https:\/\/www.who.int\/en\/activities\/tracking-SARS-CoV-2-variants\/ (Accessed: 31 May 2022)."},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Kumar S, Thambiraja TS, Karuppanan K, Subramaniam G. Omicron and Delta variant of SARS\u2010CoV\u20102: a comparative computational study of spike protein. Journal of Medical Virology. 2022; 94: 1641\u20131649.","DOI":"10.1002\/jmv.27526"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Zhan Y, Yin H, Yin JY. B.1.617.2 (Delta) Variant of SARS-CoV-2: features, transmission and potential strategies. International Journal of Biological Sciences. 2022; 18: 1844\u20131851.","DOI":"10.7150\/ijbs.66881"},{"key":"ref8","unstructured":"World Health Organization. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. 2021. Available at: https:\/\/www.who.int\/news\/item\/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern (Accessed: 31 May 2022)."},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Sigal A, Milo R, Jassat W. Estimating disease severity of Omicron and Delta SARS-CoV-2 infections. Nature Reviews Immunology. 2022; 22: 267\u2013269.","DOI":"10.1038\/s41577-022-00720-5"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Hsu RJ, Yu WC, Peng GR, Ye CH, Hu S, Chong PCT, et al. The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections. Frontiers in Immunology. 2022; 13: 832394.","DOI":"10.3389\/fimmu.2022.832394"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, Nemati M. Contribution of Monocytes and Macrophages to the Local Tissue Inflammation and Cytokine Storm in COVID-19: Lessons from SARS and MERS, and Potential Therapeutic Interventions. Life Sciences. 2020; 257: 118102.","DOI":"10.1016\/j.lfs.2020.118102"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Bao L, Deng W, Huang B, Gao H, Liu J, Ren L, et al. The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice. Nature. 2020; 583: 830\u2013833.","DOI":"10.1038\/s41586-020-2312-y"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Dong W, Mead H, Tian L, Park J, Garcia JI, Jaramillo S, et al. The K18-Human ACE2 Transgenic Mouse Model Recapitulates Non-severe and Severe COVID-19 in Response to an Infectious Dose of the SARS-CoV-2 Virus. Journal of Virology. 2022; 96: e0096421.","DOI":"10.1128\/JVI.00964-21"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Natekar JP, Pathak H, Stone S, Kumari P, Sharma S, Auroni TT, et al. Differential Pathogenesis of SARS-CoV-2 Variants of Concern in Human ACE2-Expressing Mice. Viruses. 2022; 14: 1139.","DOI":"10.3390\/v14061139"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Winkler ES, Bailey AL, Kafai NM, Nair S, McCune BT, Yu J, et al. SARS-CoV-2 infection in the lungs of human ACE2 transgenic mice causes severe inflammation, immune cell infiltration, and compromised respiratory function. BioRxiv. 2020. (preprint).","DOI":"10.1101\/2020.07.09.196188"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Takao K, Miyakawa T. Genomic responses in mouse models greatly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences. 2015; 112: 1167\u20131172.","DOI":"10.1073\/pnas.1401965111"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Jiang R, Liu M, Chen Y, Shan C, Zhou Y, Shen X, et al. Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2. Cell. 2020; 182: 50\u201358.","DOI":"10.1016\/j.cell.2020.05.027"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Park JG, Pino PA, Akhter A, Alvarez X, Torrelles JB, Martinez-Sobrido L. Animal Models of COVID-19: Transgenic Mouse Model. SARS-CoV-2 (pp. 259\u2013289). Humana: New York, NY, 2022.","DOI":"10.1007\/978-1-0716-2111-0_16"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Winkler ES, Bailey AL, Kafai NM, Nair S, McCune BT, Yu J, et al. Publisher Correction: SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function. Nature Immunology. 2020; 21: 1470\u20131470.","DOI":"10.1038\/s41590-020-0794-2"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Reed LJ and Muench H. A Simple Method of Estimating fifty Percent Endpoints. American Journal of Hygiene. 1938; 27: 493\u2013497.","DOI":"10.1093\/oxfordjournals.aje.a118408"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Chu H, Yuen K. Pathogenicity of SARS\u2010CoV\u20102 Omicron. Clinical and Translational Medicine. 2022; 12: e880.","DOI":"10.1002\/ctm2.880"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Veneti L, B\u00f8\u00e5s H, Br\u00e5then KA, St\u00e5lcrantz J, Bragstad K, Hungnes O, et al. Reduced Risk of Hospitalisation among Reported COVID-19 Cases Infected with the SARS-CoV-2 Omicron BA.1 Variant Compared with the Delta Variant, Norway, December 2021 to January 2022. Eurosurveillance Journal. 2022; 27: 2200077.","DOI":"10.2807\/1560-7917.ES.2022.27.4.2200077"},{"key":"ref23","unstructured":"Samuel Baron MF, Thomas A. Viral Pathogenesis in Medical Microbiology, Galveston (TX): University of Texas Medical Branch at Galveston, 1996."},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Natekar JP, Pathak H, Stone S, Kumari P, Sharma S, Auroni TT, et al. Differential pathogenesis of SARS-CoV-2 variants of concern in human ACE2-expressing mice. Viruses. 2022; 14: 1139.","DOI":"10.3390\/v14061139"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Halfmann PJ, Iida S, Iwatsuki-Horimoto K, Maemura T, Kiso M, Scheaffer SM, et al. SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters. Nature. 2022; 603: 706\u2013714.","DOI":"10.1038\/s41586-022-04441-6"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Shuai H, Chan JF, Hu B, Chai Y, Yuen TT, Yin F, et al. Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron. Nature. 2022; 603: 693\u2013699.","DOI":"10.1038\/s41586-022-04442-5"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Meng B, Abdullahi A, Ferreira IATM, Goonawardane N, Saito A, Kimura I, et al. Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity. Nature. 2022; 603: 706\u2013714.","DOI":"10.1038\/s41586-022-04474-x"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Kang YW, Park S, Lee KJ, Moon D, Kim YM, Lee SW. Understanding the Host Innate Immune Responses against SARS-CoV-2 Infection and COVID-19 Pathogenesis. Immune Network. 2021; 21.","DOI":"10.4110\/in.2021.21.e1"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Lee S, Channappanavar R, Kanneganti T. Coronaviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines. Trends in Immunology. 2020; 41: 1083\u20131099.","DOI":"10.1016\/j.it.2020.10.005"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Li X, Zhang Z, Wang Z, Guti\u00e9rrez-Castrell\u00f3n P, Shi H. Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19. Signal Transduction and Targeted Therapy. 2022; 7: 186.","DOI":"10.1038\/s41392-022-01043-6"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Ren Y, Wang A, Fang Y, Shu T, Wu D, Wang C, et al. SARS-CoV-2 Membrane Glycoprotein M Triggers Apoptosis with the Assistance of Nucleocapsid Protein N in Cells. Frontiers in Cellular and Infection Microbiology. 2021; 627.","DOI":"10.3389\/fcimb.2021.706252"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Huang B, Zhao J, Unkeless JC, Feng ZH, Xiong H. TLR Signaling by Tumor and Immune Cells: a Double-Edged Sword. Oncogene. 2008; 27: 218\u2013224.","DOI":"10.1038\/sj.onc.1210904"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Kayesh MEH, Kohara M, Tsukiyama KK. An Overview of Recent Insights into the Response of TLR to SARS-CoV-2 Infection and the Potential of TLR Agonists as SARS-CoV-2 Vaccine Adjuvants. Viruses. 2021; 13: 2302.","DOI":"10.3390\/v13112302"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Yokota S, Okabayashi T, Fujii N. The Battle between Virus and Host: Modulation of Toll-Like Receptor Signaling Pathways by Virus Infection. Mediators of Inflammation. 2010; 2010: 1\u201312.","DOI":"10.1155\/2010\/184328"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Sariol A, Perlman S. SARS-CoV-2 takes its Toll. Nature Immunology. 2021; 22: 801\u2013802.","DOI":"10.1038\/s41590-021-00962-w"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Zheng M, Karki R, Williams EP, Yang D, Fitzpatrick E, Vogel P, et al. TLR2 Senses the SARS-CoV-2 Envelope Protein to produce inflammatory cytokines. Nature Immunology. 2021; 22: 829\u2013838.","DOI":"10.1038\/s41590-021-00937-x"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Borish LC, Steinke JW. 2. Cytokines and Chemokines. Journal of Allergy and Clinical Immunology. 2003; 111: S460\u2013S475.","DOI":"10.1067\/mai.2003.108"},{"key":"ref38","unstructured":"Chen C, Zhang X, Ju ZY, He WF. Advances in the Research of Mechanism and Related Immunotherapy on the Cytokine Storm Induced by Coronavirus Disease 2019. Chinese Journal of Burns. 2020. 36: 471\u2013475."},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China. The Lancet. 2020; 395: 497\u2013506.","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Wang W, Liu X, Wu S, Chen S, Li Y, Nong L, et al. The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis. The Journal of Infectious Diseases. 2020; 222: 1444\u20131451.","DOI":"10.1093\/infdis\/jiaa387"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Ryzhakov G, Lai CC, Blazek K, To K, Hussell T, Udalova I. IL-17 Boosts Proinflammatory Outcome of Antiviral Response in Human Cells. The Journal of Immunology. 2011; 187: 5357\u20135362.","DOI":"10.4049\/jimmunol.1100917"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. The Lancet Respiratory Medicine. 2020; 8: 420\u2013422.","DOI":"10.1016\/S2213-2600(20)30076-X"},{"key":"ref43","unstructured":"Liu Y, Zhang C, Huang F, Yang Y, Wang F, Yuan J, et al. 2019-novel coronavirus (2019-nCoV) infections trigger an exaggerated cytokine response aggravating lung injury. 2020. Available at: http:\/\/www.chinaxiv.org\/abs\/202002.00018 (Accessed: 12 February 2020)."},{"key":"ref44","doi-asserted-by":"crossref","unstructured":"Jin J, Han X, Yu Q. Interleukin-6 induces the generation of IL-10-producing Tr1 cells and suppresses autoimmune tissue inflammation. Journal of Autoimmunity. 2013; 40: 28\u201344.","DOI":"10.1016\/j.jaut.2012.07.009"},{"key":"ref45","doi-asserted-by":"crossref","unstructured":"Saraiva M, Christensen JR, Veldhoen M, Murphy TL, Murphy KM, O\u2019Garra A. Interleukin-10 Production by Th1 Cells Requires Interleukin-12-Induced STAT4 Transcription Factor and ERK MAP Kinase Activation by High Antigen Dose. Immunity. 2009; 31: 209\u2013219.","DOI":"10.1016\/j.immuni.2009.05.012"},{"key":"ref46","doi-asserted-by":"crossref","unstructured":"Fitzgerald DC, Zhang G, El-Behi M, Fonseca-Kelly Z, Li H, Yu S, et al. Suppression of autoimmune inflammation of the central nervous system by interleukin 10 secreted by interleukin 27\u2013stimulated T cells. Nature Immunology. 2007; 8: 1372\u20131379.","DOI":"10.1038\/ni1540"},{"key":"ref47","doi-asserted-by":"crossref","unstructured":"Spolski R, Kim H, Zhu W, Levy DE, Leonard WJ. IL-21 Mediates Suppressive Effects via its Induction of IL-10. The Journal of Immunology. 2009; 182: 2859\u20132867.","DOI":"10.4049\/jimmunol.0802978"},{"key":"ref48","doi-asserted-by":"crossref","unstructured":"Cao S, Liu J, Song L, Ma X. The Protooncogene c-Maf is an Essential Transcription Factor for IL-10 Gene Expression in Macrophages. The Journal of Immunology. 2005; 174: 3484\u20133492.","DOI":"10.4049\/jimmunol.174.6.3484"},{"key":"ref49","doi-asserted-by":"crossref","unstructured":"McAdams M, Ostrosky-Frid M, Rajora N, Hedayati S. Effect of COVID-19 on Kidney Disease Incidence and Management. Kidney360. 2021; 2: 141.","DOI":"10.34067\/KID.0006362020"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"McAdams MC, Xu P, Saleh SN, Li M, Ostrosky-Frid M, Gregg LP, et al. Risk Prediction for Acute Kidney Injury in Patients Hospitalized with COVID-19. Kidney Medicine. 2022; 4: 100463.","DOI":"10.1016\/j.xkme.2022.100463"},{"key":"ref51","doi-asserted-by":"crossref","unstructured":"Morais da Silva M, Lira de Lucena AS, Paiva J\u00fanior SDSL, Flor\u00eancio De Carvalho VM, Santana de Oliveira PS, da Rosa MM, et al. Cell Death Mechanisms Involved in Cell Injury Caused by SARS\u2010CoV\u20102. Reviews in Medical Virology. 2022; 32: e2292.","DOI":"10.1002\/rmv.2292"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Ren Y, Shu T, Wu D, Mu J, Wang C, Huang M, et al. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cellular and Molecular Immunology. 2020; 17: 881\u2013883.","DOI":"10.1038\/s41423-020-0485-9"},{"key":"ref53","doi-asserted-by":"crossref","unstructured":"Bader SM, Cooney JP, Pellegrini M, Doerflinger M. Programmed Cell Death: the Pathways to Severe COVID-19? The Biochemical Journal. 2022; 479: 609\u2013628.","DOI":"10.1042\/BCJ20210602"},{"key":"ref54","doi-asserted-by":"crossref","unstructured":"Frank MG, Nguyen KH, Ball JB, Hopkins S, Kelley T, Baratta MV, et al. SARS-CoV-2 spike S1 subunit induces neuroinflammatory, microglial and behavioral sickness responses: Evidence of PAMP-like properties. Brain, Behavior, and Immunity. 2022; 100: 267\u2013277.","DOI":"10.1016\/j.bbi.2021.12.007"},{"key":"ref55","doi-asserted-by":"crossref","unstructured":"Solomon IH, Normandin E, Bhattacharyya S, Mukerji SS, Keller K, Ali AS, et al. Neuropathological Features of Covid-19. New England Journal of Medicine. 2020; 383: 989\u2013992.","DOI":"10.1056\/NEJMc2019373"},{"key":"ref56","doi-asserted-by":"crossref","unstructured":"Thakur KT, Miller EH, Glendinning MD, Al-Dalahmah O, Banu MA, Boehme AK, et al. COVID-19 Neuropathology at Columbia University Irving Medical Center\/New York Presbyterian Hospital. Brain. 2021; 144: 2696\u20132708.","DOI":"10.1093\/brain\/awab148"},{"key":"ref57","doi-asserted-by":"crossref","unstructured":"Matschke J, L\u00fctgehetmann M, Hagel C, Sperhake JP, Schr\u00f6der AS, Edler C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. The Lancet Neurology. 2020; 19: 919\u2013929.","DOI":"10.1016\/S1474-4422(20)30308-2"},{"key":"ref58","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Casta\u00f1eda A, Lu P, Geraghty AC, Song E, Lee MH, Wood J, et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell. 2022; 185: 2452\u20132468.","DOI":"10.1016\/j.cell.2022.06.008"},{"key":"ref59","doi-asserted-by":"crossref","unstructured":"Al-Aly Z, Bowe B, Xie Y. Long COVID after breakthrough SARS-CoV-2 infection. Nature Medicine. 2022; 28: 1461\u20131467.","DOI":"10.1038\/s41591-022-01840-0"},{"key":"ref60","doi-asserted-by":"crossref","unstructured":"Stefanou MI, Palaiodimou L, Bakola E, Smyrnis N, Papadopoulou M, Paraskevas GP, et al. Neurological manifestations of long-COVID syndrome: A narrative review. Therapeutic Advances in Chronic Disease. 2022; 13: 20406223221076890.","DOI":"10.1177\/20406223221076890"}],"container-title":["Frontiers in Bioscience-Landmark"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/11\/10.31083\/j.fbl2711316","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:34:11Z","timestamp":1732710851000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/FBL\/27\/11\/10.31083\/j.fbl2711316"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,30]]},"references-count":60,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022]]}},"alternative-id":["S2768-6701(22)00679-7"],"URL":"https:\/\/doi.org\/10.31083\/j.fbl2711316","relation":{},"ISSN":["2768-6701","2768-6698"],"issn-type":[{"value":"2768-6701","type":"print"},{"value":"2768-6698","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,30]]},"article-number":"316"}}