دورية أكاديمية
Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.
| العنوان: | Morphological, cellular, and molecular basis of brain infection in COVID-19 patients. |
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| المؤلفون: | Crunfli F; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Carregari VC; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Veras FP; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Silva LS; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Nogueira MH; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Antunes ASLM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Vendramini PH; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Valença AGF; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Brandão-Teles C; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Zuccoli GDS; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Reis-de-Oliveira G; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Silva-Costa LC; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Saia-Cereda VM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Smith BJ; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Codo AC; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., de Souza GF; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Muraro SP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Parise PL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Toledo-Teixeira DA; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Santos de Castro ÍM; University of São Paulo, São Paulo, 05508-220, Brazil., Melo BM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Almeida GM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Firmino EMS; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Paiva IM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Silva BMS; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Guimarães RM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Mendes ND; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Ludwig RL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Ruiz GP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Knittel TL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Davanzo GG; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Gerhardt JA; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Rodrigues PB; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Forato J; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Amorim MR; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Brunetti NS; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Martini MC; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Benatti MN; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Batah SS; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Siyuan L; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., João RB; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Aventurato ÍK; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Rabelo de Brito M; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Mendes MJ; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., da Costa BA; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Alvim MKM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., da Silva Júnior JR; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Damião LL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., de Sousa IMP; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., da Rocha ED; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Gonçalves SM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Lopes da Silva LH; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Bettini V; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Campos BM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Ludwig G; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Tavares LA; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Pontelli MC; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Viana RMM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Martins RB; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Vieira AS; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Alves-Filho JC; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Arruda E; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Podolsky-Gondim GG; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Santos MV; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Neder L; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Damasio A; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Rehen S; D'Or Institute for Research and Education, 04502001, Brazil.; Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, 21941590, Brazil., Vinolo MAR; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Munhoz CD; University of São Paulo, São Paulo, 05508-220, Brazil., Louzada-Junior P; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Oliveira RD; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Cunha FQ; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Nakaya HI; University of São Paulo, São Paulo, 05508-220, Brazil., Mauad T; University of São Paulo, São Paulo, 05508-220, Brazil., Duarte-Neto AN; University of São Paulo, São Paulo, 05508-220, Brazil., Ferraz da Silva LF; University of São Paulo, São Paulo, 05508-220, Brazil., Dolhnikoff M; University of São Paulo, São Paulo, 05508-220, Brazil., Saldiva PHN; University of São Paulo, São Paulo, 05508-220, Brazil., Farias AS; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Cendes F; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Moraes-Vieira PMM; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Fabro AT; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Sebollela A; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Proença-Modena JL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Yasuda CL; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Mori MA; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil., Cunha TM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil., Martins-de-Souza D; Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.; D'Or Institute for Research and Education, 04502001, Brazil. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Aug 30; Vol. 119 (35), pp. e2200960119. Date of Electronic Publication: 2022 Aug 11. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Brain*/pathology , Brain*/virology , COVID-19*/complications , COVID-19*/pathology , Central Nervous System Viral Diseases*/etiology , Central Nervous System Viral Diseases*/pathology , SARS-CoV-2*, Astrocytes/pathology ; Astrocytes/virology ; Humans ; Post-Acute COVID-19 Syndrome |
| مستخلص: | Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of "long COVID-19" syndrome) has been frequently observed after mild infection. We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain. Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes. Supporting the hypothesis of astrocyte infection, neural stem cell-derived human astrocytes in vitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spike-NRP1 interaction. SARS-CoV-2-infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability. Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients. |
| References: | Neurobiol Dis. 2020 Dec;146:105131. (PMID: 33053430) Signal Transduct Target Ther. 2021 Sep 6;6(1):337. (PMID: 34489403) Eur J Neurol. 2020 Sep;27(9):e43-e44. (PMID: 32383343) Emerg Infect Dis. 2004 Feb;10(2):342-4. (PMID: 15030709) Acta Neuropathol. 2020 Jul;140(1):1-6. (PMID: 32449057) EMBO J. 2020 Oct 15;39(20):e106230. (PMID: 32876341) J Neurochem. 2022 Jul 26;:. (PMID: 35880385) Neurobiol Aging. 2021 Jul;103:68-77. (PMID: 33845398) Science. 2020 Nov 13;370(6518):856-860. (PMID: 33082293) J Neuroimmune Pharmacol. 2021 Mar;16(1):4-6. (PMID: 33405097) Sci Rep. 2021 Jan 11;11(1):413. (PMID: 33432067) Brain Behav Immun. 2020 Oct;89:569-578. (PMID: 32561221) J Cereb Blood Flow Metab. 2009 Nov;29(11):1780-9. (PMID: 19675565) J Neurol Sci. 2020 Aug 15;415:116969. (PMID: 32570113) EClinicalMedicine. 2020 Aug;25:100484. (PMID: 32838240) Nature. 2017 Jan 26;541(7638):481-487. (PMID: 28099414) Ann N Y Acad Sci. 2007 Dec;1121:546-61. (PMID: 17698998) Nat Commun. 2020 Jul 27;11(1):3753. (PMID: 32719333) Trends Neurosci. 2020 Jun;43(6):355-357. (PMID: 32359765) Nat Neurosci. 2017 Mar;20(3):393-395. (PMID: 28135241) J Cereb Blood Flow Metab. 2007 Nov;27(11):1766-91. (PMID: 17579656) Science. 2020 Nov 13;370(6518):861-865. (PMID: 33082294) Trends Mol Med. 2019 Feb;25(2):77-95. (PMID: 30611668) J Neurochem. 2006 Aug;98(3):641-53. (PMID: 16787421) JAMA Neurol. 2020 Aug 1;77(8):1028-1029. (PMID: 32469400) Lancet. 2020 Mar 28;395(10229):1054-1062. (PMID: 32171076) Clin Chem. 2003 Dec;49(12):2108-9. (PMID: 14633896) Clin Res Cardiol. 2020 May;109(5):531-538. (PMID: 32161990) Nature. 2021 Nov;599(7883):102-107. (PMID: 34616039) J Cereb Blood Flow Metab. 2012 Jul;32(7):1152-66. (PMID: 22027938) Clin Infect Dis. 2005 Oct 15;41(8):1089-96. (PMID: 16163626) Eur J Neurosci. 2011 Apr;33(8):1483-92. (PMID: 21395864) Nat Commun. 2020 Nov 30;11(1):6122. (PMID: 33257679) Cereb Cortex. 2022 Feb 25;:. (PMID: 35212358) Nature. 2022 Apr;604(7907):697-707. (PMID: 35255491) Brain Behav Immun. 2020 Jul;87:34-39. (PMID: 32298803) Mol Neurobiol. 2021 Feb;58(2):520-535. (PMID: 32978729) Nat Neurosci. 2017 Feb 23;20(3):382-384. (PMID: 28230843) Cell Rep. 2020 Jun 23;31(12):107776. (PMID: 32579912) Emerg Microbes Infect. 2020 Dec;9(1):1712-1721. (PMID: 32619390) Lancet Psychiatry. 2020 Oct;7(10):875-882. (PMID: 32593341) Cell Stem Cell. 2020 Dec 3;27(6):937-950.e9. (PMID: 33010822) Nat Neurosci. 2021 Feb;24(2):168-175. (PMID: 33257876) Cell. 2011 Mar 4;144(5):810-23. (PMID: 21376239) Brain. 2021 May 7;144(4):1263-1276. (PMID: 33822001) Crit Care. 2020 Apr 28;24(1):176. (PMID: 32345343) Cell Host Microbe. 2020 Sep 9;28(3):475-485.e5. (PMID: 32735849) Lancet Psychiatry. 2020 Jul;7(7):611-627. (PMID: 32437679) Nature. 2021 Jun;594(7862):246-252. (PMID: 33845483) Neuropharmacology. 2010 Feb;58(2):465-73. (PMID: 19747495) Neuroimage Clin. 2016 Dec 07;13:215-222. (PMID: 28003960) Prog Neuropsychopharmacol Biol Psychiatry. 2018 Dec 20;87(Pt A):126-146. (PMID: 28989099) Cell Metab. 2011 Dec 7;14(6):724-38. (PMID: 22152301) Front Neurol. 2020 Dec 11;11:587384. (PMID: 33362695) Cereb Cortex. 2022 Mar 07;:. (PMID: 35253859) Trends Neurosci. 2013 Oct;36(10):587-97. (PMID: 23968694) Mol Psychiatry. 2022 Apr;27(4):2052-2060. (PMID: 35145230) Science. 2008 Dec 5;322(5907):1551-5. (PMID: 19056987) Lancet Neurol. 2020 Nov;19(11):919-929. (PMID: 33031735) J Cereb Blood Flow Metab. 2011 Feb;31(2):494-503. (PMID: 20664610) Int J Infect Dis. 2020 May;94:55-58. (PMID: 32251791) Nat Neurosci. 2021 Mar;24(3):312-325. (PMID: 33589835) Am J Clin Nutr. 2009 Sep;90(3):875S-880S. (PMID: 19571222) J Neurol. 2022 Jan;269(1):44-46. (PMID: 34143277) Life Sci. 2020 Sep 15;257:118063. (PMID: 32652139) Nature. 2021 Jan;589(7843):603-607. (PMID: 33166988) Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2823-2833. (PMID: 33501506) Signal Transduct Target Ther. 2020 Dec 4;5(1):283. (PMID: 33277466) Dialogues Clin Neurosci. 2009;11(3):281-95. (PMID: 19877496) Cell Stem Cell. 2021 Feb 4;28(2):331-342.e5. (PMID: 33450186) Cell Stem Cell. 2020 Dec 3;27(6):951-961.e5. (PMID: 33113348) Nat Med. 2018 Jul;24(7):931-938. (PMID: 29892066) Autism. 2017 Jan;21(1):18-28. (PMID: 26975670) Brain Behav Immun. 2020 Jul;87:149. (PMID: 32387508) Cell Res. 2020 Oct;30(10):928-931. (PMID: 32753756) Nat Med. 2020 Jul;26(7):1017-1032. (PMID: 32651579) J Clin Invest. 2021 Apr 15;131(8):. (PMID: 33630760) Alzheimer Dis Assoc Disord. 2022 Apr-Jun 01;36(2):173-175. (PMID: 34966022) Nat Med. 2021 Sep;27(9):1600-1606. (PMID: 34244682) Neurol Neuroimmunol Neuroinflamm. 2022 Mar 7;9(3):. (PMID: 35256481) Cell. 2020 Apr 16;181(2):271-280.e8. (PMID: 32142651) Cell Transplant. 2011;20(3):431-40. (PMID: 20719082) Nature. 2020 Jul;583(7816):469-472. (PMID: 32408336) Eur Geriatr Med. 2020 Oct;11(5):857-862. (PMID: 32666303) Eur J Nucl Med Mol Imaging. 2021 Aug;48(9):2674-2675. (PMID: 33813593) Lancet Respir Med. 2020 May;8(5):475-481. (PMID: 32105632) Nat Med. 2021 Apr;27(4):601-615. (PMID: 33753937) J Neurochem. 2009 Oct;111(2):522-36. (PMID: 19682206) Nature. 2021 Jul;595(7868):565-571. (PMID: 34153974) J Virol. 2006 May;80(10):5059-64. (PMID: 16641297) JAMA Neurol. 2020 Jun 1;77(6):683-690. (PMID: 32275288) Neurology. 2020 May 12;94(19):e2026-e2036. (PMID: 32291295) |
| فهرسة مساهمة: | Keywords: COVID-19; NRP1; SARS-CoV-2; astrocytes; neurological symptoms |
| تواريخ الأحداث: | Date Created: 20220811 Date Completed: 20220815 Latest Revision: 20221207 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9436354 |
| DOI: | 10.1073/pnas.2200960119 |
| PMID: | 35951647 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
|---|---|
| DOI: | 10.1073/pnas.2200960119 |