ArticleProceedings of the National Academy of Sciences of the United States of America2022
Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.
Open access · greenAbstract read
In one paragraph
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 5 pooled it
31.9field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
168 citing papers in PubMed, 5 syntheses or guidelines pooled it, 269 citations in OpenAlex.
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Gender Disparities in Neurological Symptoms of Long COVID: A Systematic Review and Meta-Analysis.Neuroepidemiology · 2025Pooled it
- Intervention modalities for brain fog caused by long-COVID: systematic review of the literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Pathophysiological Mechanisms in Long COVID: A Mixed Method Systematic Review.International journal of environmental research and public health · 2024Pooled it
- Topographical Distribution of Neuroanatomical Abnormalities Following COVID-19 Invasion : A Systematic Literature Review.Clinical neuroradiology · 2024Pooled it
- Real world research on transcranial magnetic stimulation treatment strategies for neuropsychiatric symptoms with long-COVID in Japan.Asian journal of psychiatry · 2023Trial
- Article
- Proteomic and Phosphoproteomic Characteristics of Multiple Brain Regions in Rhesus Macaques After SARS-CoV-2 Infection.MedComm · 2026Article
- Targeting Neutrophil Extracellular Traps in Neuroinflammation: A Therapeutic Perspective on Neurodegenerative Diseases.Brain sciences · 2026Review
- Understanding neuroinflammation in post-COVID-19 syndrome: biological mechanisms, diagnostic biomarkers, and therapeutic prospects.Translational psychiatry · 2026Review
- Convergence of neuroinflammation across major neurotropic viral exposomes in AD and ADRD.Journal of neuroinflammation · 2026Review
- Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID.Communications medicine · 2026Article
- COVID-19 and risk of first-time major depressive disorder in patients without history of psychiatric disorders.BMC psychiatry · 2026Observational
- LearningRx Cognitive Training for Workplace Self-Efficacy in Adults with Post-COVID-19 Brain Fog: A Mixed-Methods Pilot Study.Brain sciences · 2026Article
- Metabolomics Highlights Reduced Glutamate and Acetylcarnitine in the Amniotic Fluid of Cytomegalovirus-Infected Pregnant Women.Journal of proteome research · 2026Article
- MRI of Syrian hamsters reveals SARS-CoV-2 variant-specific neuroinflammation.Microbiology spectrum · 2026Article
- Identifying GFAP-expressing cell susceptibility to SARS-CoV-2 infection using human iPSC-derived neural cells.Scientific reports · 2026Article
- Spatial multiomics dissects the SARS-CoV-2-induced disruption of cell adhesion and immune dynamics in the human hippocampus.Journal of neuroinflammation · 2026Article
- Mild chronic hypoxia and the brain: an ambiguous relationship.Journal of neuroinflammation · 2026Review
- Synergy of SARS-CoV-2 and HIV-1 Infections in the Human Brain.Pathogens (Basel, Switzerland) · 2026Review
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
88 authors at 3 institutions in 1 country.
Fernanda CrunfliDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-2968-8115
Victor C CarregariDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-6863-1333
Flavio P VerasRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Lucas S SilvaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Mateus Henrique NogueiraDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-9085-6990
André Saraiva Leão Marcelo AntunesDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-0692-8948
Pedro Henrique VendraminiDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Aline Gazzola Fragnani ValençaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Caroline Brandão-TelesDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Giuliana da Silva ZuccoliDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Guilherme Reis-de-OliveiraDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Lícia C Silva-CostaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Verônica Monteiro Saia-CeredaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Bradley J SmithDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0003-1383-5851
Ana Campos CodoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-9036-5772
Gabriela F de SouzaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-7285-0790
Stéfanie P MuraroDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Pierina Lorencini PariseDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0003-2818-1301
Daniel A Toledo-TeixeiraDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Ícaro Maia Santos de CastroUniversity of São Paulo, São Paulo, 05508-220, Brazil.ORCID 0000-0002-3484-8718
Bruno Marcel MeloRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Glaucia M AlmeidaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0003-4149-5313
Egidi Mayara Silva FirminoRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Isadora Marques PaivaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-2741-150X
Bruna Manuella Souza SilvaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Rafaela Mano GuimarãesRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-2182-4215
Niele D MendesRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0003-4266-8546
Raíssa L LudwigDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Gabriel P RuizDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Thiago L KnittelDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-5716-2033
Gustavo G DavanzoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-6723-1933
Jaqueline Aline GerhardtDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Patrícia Brito RodriguesDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Julia ForatoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Mariene Ribeiro AmorimDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-8516-0155
Natália S BrunettiDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Matheus Cavalheiro MartiniDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Maíra Nilson BenattiRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Sabrina S BatahRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Li SiyuanRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-8136-1021
Rafael B JoãoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Ítalo K AventuratoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-9314-1109
Mariana Rabelo de BritoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Maria J MendesDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Beatriz A da CostaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-8035-7701
Marina K M AlvimDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
José Roberto da Silva JúniorDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Lívia L DamiãoDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Iêda Maria P de SousaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Elessandra D da RochaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Solange M GonçalvesDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Luiz H Lopes da SilvaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Vanessa BettiniDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Brunno M CamposDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0003-1261-8257
Guilherme LudwigDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0003-4526-3798
Lucas Alves TavaresRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0001-7883-1443
Marjorie Cornejo PontelliRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0003-3173-5977
Rosa Maria Mendes VianaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Ronaldo B MartinsRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-8902-5962
Andre Schwambach VieiraDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
José Carlos Alves-FilhoRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-9918-8714
Eurico ArrudaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-0978-410X
Guilherme Gozzoli Podolsky-GondimRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-9608-2607
Marcelo Volpon SantosRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Luciano NederRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
André DamasioDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-9304-3998
Stevens RehenD'Or Institute for Research and Education, 04502001, Brazil.ORCID 0000-0003-4216-9501
Marco Aurélio Ramirez VinoloDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Carolina Demarchi MunhozUniversity of São Paulo, São Paulo, 05508-220, Brazil.
Paulo Louzada-JuniorRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0003-2585-3870
Renê Donizeti OliveiraRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Fernando Q CunhaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Helder I NakayaUniversity of São Paulo, São Paulo, 05508-220, Brazil.ORCID 0000-0001-5297-9108
Thais MauadUniversity of São Paulo, São Paulo, 05508-220, Brazil.
Amaro Nunes Duarte-NetoUniversity of São Paulo, São Paulo, 05508-220, Brazil.
Luiz Fernando Ferraz da SilvaUniversity of São Paulo, São Paulo, 05508-220, Brazil.ORCID 0000-0002-0181-6357
Marisa DolhnikoffUniversity of São Paulo, São Paulo, 05508-220, Brazil.
Paulo Hilario Nascimento SaldivaUniversity of São Paulo, São Paulo, 05508-220, Brazil.
Alessandro S FariasDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Fernando CendesDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-9336-9568
Pedro Manoel M Moraes-VieiraDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-8263-786X
Alexandre T FabroRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Adriano SebollelaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.ORCID 0000-0002-7444-9156
José L Proença-ModenaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0002-4996-3153
Clarissa L YasudaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-9084-7173
Marcelo A MoriDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.ORCID 0000-0001-7112-5263
Thiago M CunhaRibeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049900, Brazil.
Daniel Martins-de-SouzaDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, 13083862, Brazil.
Universidade Estadual de Campinas (UNICAMP) · BRUniversidade de São Paulo · BRUniversidade Federal do Rio de Janeiro · BR
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
Indexed as
BrainCentral Nervous System Viral DiseasesCOVID-19SARS-CoV-2AstrocytesHumansPost-Acute COVID-19 SyndromeastrocytesCOVID-19neurological symptomsNRP1SARS-CoV-2
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.