Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Summary: Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with C...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-05-01
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| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379121001166 |
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doaj-13598675c04e4b9aa6e8c523385b4bf1 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Eric Song Christopher M. Bartley Ryan D. Chow Thomas T. Ngo Ruoyi Jiang Colin R. Zamecnik Ravi Dandekar Rita P. Loudermilk Yile Dai Feimei Liu Sara Sunshine Jamin Liu Wesley Wu Isobel A. Hawes Bonny D. Alvarenga Trung Huynh Lindsay McAlpine Nur-Taz Rahman Bertie Geng Jennifer Chiarella Benjamin Goldman-Israelow Chantal B.F. Vogels Nathan D. Grubaugh Arnau Casanovas-Massana Brett S. Phinney Michelle Salemi Jessa R. Alexander Juan A. Gallego Todd Lencz Hannah Walsh Anne E. Wapniarski Subhasis Mohanty Carolina Lucas Jon Klein Tianyang Mao Jieun Oh Aaron Ring Serena Spudich Albert I. Ko Steven H. Kleinstein John Pak Joseph L. DeRisi Akiko Iwasaki Samuel J. Pleasure Michael R. Wilson Shelli F. Farhadian |
| spellingShingle |
Eric Song Christopher M. Bartley Ryan D. Chow Thomas T. Ngo Ruoyi Jiang Colin R. Zamecnik Ravi Dandekar Rita P. Loudermilk Yile Dai Feimei Liu Sara Sunshine Jamin Liu Wesley Wu Isobel A. Hawes Bonny D. Alvarenga Trung Huynh Lindsay McAlpine Nur-Taz Rahman Bertie Geng Jennifer Chiarella Benjamin Goldman-Israelow Chantal B.F. Vogels Nathan D. Grubaugh Arnau Casanovas-Massana Brett S. Phinney Michelle Salemi Jessa R. Alexander Juan A. Gallego Todd Lencz Hannah Walsh Anne E. Wapniarski Subhasis Mohanty Carolina Lucas Jon Klein Tianyang Mao Jieun Oh Aaron Ring Serena Spudich Albert I. Ko Steven H. Kleinstein John Pak Joseph L. DeRisi Akiko Iwasaki Samuel J. Pleasure Michael R. Wilson Shelli F. Farhadian Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms Cell Reports Medicine COVID-19 neurological infection autoimmunity cerebrospinal fluid SARS-CoV-2 |
| author_facet |
Eric Song Christopher M. Bartley Ryan D. Chow Thomas T. Ngo Ruoyi Jiang Colin R. Zamecnik Ravi Dandekar Rita P. Loudermilk Yile Dai Feimei Liu Sara Sunshine Jamin Liu Wesley Wu Isobel A. Hawes Bonny D. Alvarenga Trung Huynh Lindsay McAlpine Nur-Taz Rahman Bertie Geng Jennifer Chiarella Benjamin Goldman-Israelow Chantal B.F. Vogels Nathan D. Grubaugh Arnau Casanovas-Massana Brett S. Phinney Michelle Salemi Jessa R. Alexander Juan A. Gallego Todd Lencz Hannah Walsh Anne E. Wapniarski Subhasis Mohanty Carolina Lucas Jon Klein Tianyang Mao Jieun Oh Aaron Ring Serena Spudich Albert I. Ko Steven H. Kleinstein John Pak Joseph L. DeRisi Akiko Iwasaki Samuel J. Pleasure Michael R. Wilson Shelli F. Farhadian |
| author_sort |
Eric Song |
| title |
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms |
| title_short |
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms |
| title_full |
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms |
| title_fullStr |
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms |
| title_full_unstemmed |
Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms |
| title_sort |
divergent and self-reactive immune responses in the cns of covid-19 patients with neurological symptoms |
| publisher |
Elsevier |
| series |
Cell Reports Medicine |
| issn |
2666-3791 |
| publishDate |
2021-05-01 |
| description |
Summary: Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19. |
| topic |
COVID-19 neurological infection autoimmunity cerebrospinal fluid SARS-CoV-2 |
| url |
http://www.sciencedirect.com/science/article/pii/S2666379121001166 |
| work_keys_str_mv |
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1721434058684104704 |
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doaj-13598675c04e4b9aa6e8c523385b4bf12021-05-20T07:53:15ZengElsevierCell Reports Medicine2666-37912021-05-0125100288Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptomsEric Song0Christopher M. Bartley1Ryan D. Chow2Thomas T. Ngo3Ruoyi Jiang4Colin R. Zamecnik5Ravi Dandekar6Rita P. Loudermilk7Yile Dai8Feimei Liu9Sara Sunshine10Jamin Liu11Wesley Wu12Isobel A. Hawes13Bonny D. Alvarenga14Trung Huynh15Lindsay McAlpine16Nur-Taz Rahman17Bertie Geng18Jennifer Chiarella19Benjamin Goldman-Israelow20Chantal B.F. Vogels21Nathan D. Grubaugh22Arnau Casanovas-Massana23Brett S. Phinney24Michelle Salemi25Jessa R. Alexander26Juan A. Gallego27Todd Lencz28Hannah Walsh29Anne E. Wapniarski30Subhasis Mohanty31Carolina Lucas32Jon Klein33Tianyang Mao34Jieun Oh35Aaron Ring36Serena Spudich37Albert I. Ko38Steven H. Kleinstein39John Pak40Joseph L. DeRisi41Akiko Iwasaki42Samuel J. Pleasure43Michael R. Wilson44Shelli F. Farhadian45Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Corresponding authorHanna H. Gray Fellow, Howard Hughes Medical Institute, Chevy Chase, MD, USA; Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USADepartment of Genetics, Yale School of Medicine, New Haven, CT, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USADepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; University of California, Berkeley—University of California, San Francisco Gradate Program in Bioengineering, Berkeley, CA, USAChan Zuckerberg Biohub, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Neurology, Yale School of Medicine, New Haven, CT, USADepartment of Neurology, Yale School of Medicine, New Haven, CT, USADepartment of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USADepartment of Neurology, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Bioinformatics Support Program, Cushing/Whitney Medical Library, Yale University School of Medicine, New Haven, CT, USADepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USADepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USADepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USAProteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USAProteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USAInstitute for Behavioral Science, The Feinstein Institute for Medical Research, Manhasset, NY, USA; Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USAInstitute for Behavioral Science, The Feinstein Institute for Medical Research, Manhasset, NY, USA; Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USADepartment of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USADepartment of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USADepartment of Neurology, Yale School of Medicine, New Haven, CT, USADepartment of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Department of Pathology, Yale School of Medicine, New Haven, CT, USA; Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USAChan Zuckerberg Biohub, San Francisco, CA, USADepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USADepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA; Department of Molecular, Cellular, and Developmental Biology, Yale School of Medicine, New Haven, CT, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USAWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Corresponding authorWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Corresponding authorDepartment of Neurology, Yale School of Medicine, New Haven, CT, USA; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA; Corresponding authorSummary: Individuals with coronavirus disease 2019 (COVID-19) frequently develop neurological symptoms, but the biological underpinnings of these phenomena are unknown. Through single-cell RNA sequencing (scRNA-seq) and cytokine analyses of cerebrospinal fluid (CSF) and blood from individuals with COVID-19 with neurological symptoms, we find compartmentalized, CNS-specific T cell activation and B cell responses. All affected individuals had CSF anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies whose target epitopes diverged from serum antibodies. In an animal model, we find that intrathecal SARS-CoV-2 antibodies are present only during brain infection and not elicited by pulmonary infection. We produced CSF-derived monoclonal antibodies from an individual with COVID-19 and found that these monoclonal antibodies (mAbs) target antiviral and antineural antigens, including one mAb that reacted to spike protein and neural tissue. CSF immunoglobulin G (IgG) from 5 of 7 patients showed antineural reactivity. This immune survey reveals evidence of a compartmentalized immune response in the CNS of individuals with COVID-19 and suggests a role of autoimmunity in neurologic sequelae of COVID-19.http://www.sciencedirect.com/science/article/pii/S2666379121001166COVID-19neurological infectionautoimmunitycerebrospinal fluidSARS-CoV-2 |