Anti–SARS-CoV-2 and Autoantibody Profiles in the Cerebrospinal Fluid of 3 Teenaged Patients With COVID-19 and Subacute Neuropsychiatric Symptoms
IMPORTANCE: Neuropsychiatric manifestations of COVID-19 have been reported in the pediatric population. OBJECTIVE: To determine whether anti–SARS-CoV-2 and autoreactive antibodies are present in the cerebrospinal fluid (CSF) of pediatric patients with COVID-19 and subacute neuropsychiatric dysfuncti...
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| Veröffentlicht in: | Archives of neurology (Chicago) 2021-12, Vol.78 (12), p.1503-1509 |
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| creator | Bartley, Christopher M Johns, Claire Ngo, Thomas T Dandekar, Ravi Loudermilk, Rita L Alvarenga, Bonny D Hawes, Isobel A Zamecnik, Colin R Zorn, Kelsey C Alexander, Jessa R Wapniarski, Anne E DeRisi, Joseph L Francisco, Carla Nash, Kendall B Wietstock, Sharon O Pleasure, Samuel J Wilson, Michael R |
| description | IMPORTANCE: Neuropsychiatric manifestations of COVID-19 have been reported in the pediatric population. OBJECTIVE: To determine whether anti–SARS-CoV-2 and autoreactive antibodies are present in the cerebrospinal fluid (CSF) of pediatric patients with COVID-19 and subacute neuropsychiatric dysfunction. DESIGN, SETTING, AND PARTICIPANTS: This case series includes 3 patients with recent SARS-CoV-2 infection as confirmed by reverse transcriptase–polymerase chain reaction or IgG serology with recent exposure history who were hospitalized at the University of California, San Francisco Benioff Children’s Hospital and for whom a neurology consultation was requested over a 5-month period in 2020. During this period, 18 total children were hospitalized and tested positive for acute SARS-CoV-2 infection by reverse transcriptase–polymerase chain reaction or rapid antigen test. MAIN OUTCOMES AND MEASURES: Detection and characterization of CSF anti–SARS-CoV-2 IgG and antineural antibodies. RESULTS: Of 3 included teenaged patients, 2 patients had intrathecal anti–SARS-CoV-2 antibodies. CSF IgG from these 2 patients also indicated antineural autoantibodies on anatomic immunostaining. Autoantibodies targeting transcription factor 4 (TCF4) in 1 patient who appeared to have a robust response to immunotherapy were also validated. CONCLUSIONS AND RELEVANCE: Pediatric patients with COVID-19 and prominent subacute neuropsychiatric symptoms, ranging from severe anxiety to delusional psychosis, may have anti–SARS-CoV-2 and antineural antibodies in their CSF and may respond to immunotherapy. |
| doi_str_mv | 10.1001/jamaneurol.2021.3821 |
| format | Article |
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OBJECTIVE: To determine whether anti–SARS-CoV-2 and autoreactive antibodies are present in the cerebrospinal fluid (CSF) of pediatric patients with COVID-19 and subacute neuropsychiatric dysfunction. DESIGN, SETTING, AND PARTICIPANTS: This case series includes 3 patients with recent SARS-CoV-2 infection as confirmed by reverse transcriptase–polymerase chain reaction or IgG serology with recent exposure history who were hospitalized at the University of California, San Francisco Benioff Children’s Hospital and for whom a neurology consultation was requested over a 5-month period in 2020. During this period, 18 total children were hospitalized and tested positive for acute SARS-CoV-2 infection by reverse transcriptase–polymerase chain reaction or rapid antigen test. MAIN OUTCOMES AND MEASURES: Detection and characterization of CSF anti–SARS-CoV-2 IgG and antineural antibodies. RESULTS: Of 3 included teenaged patients, 2 patients had intrathecal anti–SARS-CoV-2 antibodies. CSF IgG from these 2 patients also indicated antineural autoantibodies on anatomic immunostaining. Autoantibodies targeting transcription factor 4 (TCF4) in 1 patient who appeared to have a robust response to immunotherapy were also validated. CONCLUSIONS AND RELEVANCE: Pediatric patients with COVID-19 and prominent subacute neuropsychiatric symptoms, ranging from severe anxiety to delusional psychosis, may have anti–SARS-CoV-2 and antineural antibodies in their CSF and may respond to immunotherapy.</description><identifier>ISSN: 2168-6149</identifier><identifier>EISSN: 2168-6157</identifier><identifier>DOI: 10.1001/jamaneurol.2021.3821</identifier><identifier>PMID: 34694339</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Adolescent ; Animals ; Antibodies ; Antibodies, Viral - cerebrospinal fluid ; Antigens ; Anxiety - etiology ; Anxiety - psychology ; Autoantibodies ; Autoantibodies - cerebrospinal fluid ; Autoimmunity ; Brief Report ; Cerebrospinal fluid ; Children ; Comments ; Coronaviruses ; COVID-19 ; COVID-19 - complications ; COVID-19 - immunology ; Female ; Humans ; Immunoglobulin G ; Immunotherapy ; Infections ; Male ; Marijuana Smoking - immunology ; Mental disorders ; Mental Disorders - cerebrospinal fluid ; Mental Disorders - etiology ; Mice ; Movement Disorders - etiology ; Nervous System Diseases - cerebrospinal fluid ; Nervous System Diseases - etiology ; Neurologic Examination ; Neurology ; Online First ; Patients ; Pediatrics ; Polymerase chain reaction ; Psychosis ; RNA-directed DNA polymerase ; Serology ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Teenagers ; Transcription Factor 4 - immunology ; Viral diseases</subject><ispartof>Archives of neurology (Chicago), 2021-12, Vol.78 (12), p.1503-1509</ispartof><rights>Copyright American Medical Association Dec 2021</rights><rights>Copyright 2021 Bartley CM et al. .</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a506t-a423a12430781b8e96b1093a1b05910a62b57c7a657a1ceaa149047f9bccd6b73</citedby><cites>FETCH-LOGICAL-a506t-a423a12430781b8e96b1093a1b05910a62b57c7a657a1ceaa149047f9bccd6b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamaneurology/articlepdf/10.1001/jamaneurol.2021.3821$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2021.3821$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,776,780,881,3327,27901,27902,76231,76234</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34694339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bartley, Christopher M</creatorcontrib><creatorcontrib>Johns, Claire</creatorcontrib><creatorcontrib>Ngo, Thomas T</creatorcontrib><creatorcontrib>Dandekar, Ravi</creatorcontrib><creatorcontrib>Loudermilk, Rita L</creatorcontrib><creatorcontrib>Alvarenga, Bonny D</creatorcontrib><creatorcontrib>Hawes, Isobel A</creatorcontrib><creatorcontrib>Zamecnik, Colin R</creatorcontrib><creatorcontrib>Zorn, Kelsey C</creatorcontrib><creatorcontrib>Alexander, Jessa R</creatorcontrib><creatorcontrib>Wapniarski, Anne E</creatorcontrib><creatorcontrib>DeRisi, Joseph L</creatorcontrib><creatorcontrib>Francisco, Carla</creatorcontrib><creatorcontrib>Nash, Kendall B</creatorcontrib><creatorcontrib>Wietstock, Sharon O</creatorcontrib><creatorcontrib>Pleasure, Samuel J</creatorcontrib><creatorcontrib>Wilson, Michael R</creatorcontrib><title>Anti–SARS-CoV-2 and Autoantibody Profiles in the Cerebrospinal Fluid of 3 Teenaged Patients With COVID-19 and Subacute Neuropsychiatric Symptoms</title><title>Archives of neurology (Chicago)</title><addtitle>JAMA Neurol</addtitle><description>IMPORTANCE: Neuropsychiatric manifestations of COVID-19 have been reported in the pediatric population. OBJECTIVE: To determine whether anti–SARS-CoV-2 and autoreactive antibodies are present in the cerebrospinal fluid (CSF) of pediatric patients with COVID-19 and subacute neuropsychiatric dysfunction. DESIGN, SETTING, AND PARTICIPANTS: This case series includes 3 patients with recent SARS-CoV-2 infection as confirmed by reverse transcriptase–polymerase chain reaction or IgG serology with recent exposure history who were hospitalized at the University of California, San Francisco Benioff Children’s Hospital and for whom a neurology consultation was requested over a 5-month period in 2020. During this period, 18 total children were hospitalized and tested positive for acute SARS-CoV-2 infection by reverse transcriptase–polymerase chain reaction or rapid antigen test. MAIN OUTCOMES AND MEASURES: Detection and characterization of CSF anti–SARS-CoV-2 IgG and antineural antibodies. RESULTS: Of 3 included teenaged patients, 2 patients had intrathecal anti–SARS-CoV-2 antibodies. CSF IgG from these 2 patients also indicated antineural autoantibodies on anatomic immunostaining. Autoantibodies targeting transcription factor 4 (TCF4) in 1 patient who appeared to have a robust response to immunotherapy were also validated. CONCLUSIONS AND RELEVANCE: Pediatric patients with COVID-19 and prominent subacute neuropsychiatric symptoms, ranging from severe anxiety to delusional psychosis, may have anti–SARS-CoV-2 and antineural antibodies in their CSF and may respond to immunotherapy.</description><subject>Adolescent</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Viral - cerebrospinal fluid</subject><subject>Antigens</subject><subject>Anxiety - etiology</subject><subject>Anxiety - psychology</subject><subject>Autoantibodies</subject><subject>Autoantibodies - cerebrospinal fluid</subject><subject>Autoimmunity</subject><subject>Brief Report</subject><subject>Cerebrospinal fluid</subject><subject>Children</subject><subject>Comments</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - complications</subject><subject>COVID-19 - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Immunotherapy</subject><subject>Infections</subject><subject>Male</subject><subject>Marijuana Smoking - immunology</subject><subject>Mental disorders</subject><subject>Mental Disorders - cerebrospinal fluid</subject><subject>Mental Disorders - etiology</subject><subject>Mice</subject><subject>Movement Disorders - etiology</subject><subject>Nervous System Diseases - cerebrospinal fluid</subject><subject>Nervous System Diseases - etiology</subject><subject>Neurologic Examination</subject><subject>Neurology</subject><subject>Online First</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Polymerase chain reaction</subject><subject>Psychosis</subject><subject>RNA-directed DNA polymerase</subject><subject>Serology</subject><subject>Severe acute respiratory syndrome</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Teenagers</subject><subject>Transcription Factor 4 - immunology</subject><subject>Viral diseases</subject><issn>2168-6149</issn><issn>2168-6157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUc1u1DAYjBCIVqUvgBCyxIVLFv_FSS5Iq0ChUkUrtpSj9dlxul4l8dZ2kPbGM8Ab8iQ4bFl-fLHlmW88nsmyZwQvCMbk1QYGGM3kXb-gmJIFqyh5kB1TIqpckKJ8eDjz-ig7DWGD06ow5ow_zo4YFzVnrD7Ovi3HaH98_b5aflzljbvJKYKxRcspOkiIcu0OXXnX2d4EZEcU1wY1xhvlXdjaEXp01k-2Ra5DDF0bM8KtadEVRGvGGNBnG9eoubw5f5OT-pfyalKgp2jQh9n-Nuz02kL0VqPVbthGN4Qn2aMO-mBO7_eT7NPZ2-vmfX5x-e68WV7kUGARc-CUAaGc4bIiqjK1UATX6UrhoiYYBFVFqUsQRQlEG4AUBeZlVyutW6FKdpK93utuJzWYVifDHnq59XYAv5MOrPwXGe1a3rovsiq4EJQmgZf3At7dTSZEOdigTd-natwUJC2qoqackvmtF_9RN27yKb7EEgQTwjkRicX3LJ3SDd50BzMEy7l3-ad3Ofcu597T2PO_P3IY-t1yIjzdE9L0AaVlVWBG2U-xC7WD</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Bartley, Christopher M</creator><creator>Johns, Claire</creator><creator>Ngo, Thomas T</creator><creator>Dandekar, Ravi</creator><creator>Loudermilk, Rita L</creator><creator>Alvarenga, Bonny D</creator><creator>Hawes, Isobel A</creator><creator>Zamecnik, Colin R</creator><creator>Zorn, Kelsey C</creator><creator>Alexander, Jessa R</creator><creator>Wapniarski, Anne E</creator><creator>DeRisi, Joseph L</creator><creator>Francisco, Carla</creator><creator>Nash, Kendall B</creator><creator>Wietstock, Sharon O</creator><creator>Pleasure, Samuel J</creator><creator>Wilson, Michael R</creator><general>American Medical Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20211201</creationdate><title>Anti–SARS-CoV-2 and Autoantibody Profiles in the Cerebrospinal Fluid of 3 Teenaged Patients With COVID-19 and Subacute Neuropsychiatric Symptoms</title><author>Bartley, Christopher M ; Johns, Claire ; Ngo, Thomas T ; Dandekar, Ravi ; Loudermilk, Rita L ; Alvarenga, Bonny D ; Hawes, Isobel A ; Zamecnik, Colin R ; Zorn, Kelsey C ; Alexander, Jessa R ; Wapniarski, Anne E ; DeRisi, Joseph L ; Francisco, Carla ; Nash, Kendall B ; Wietstock, Sharon O ; Pleasure, Samuel J ; Wilson, Michael R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a506t-a423a12430781b8e96b1093a1b05910a62b57c7a657a1ceaa149047f9bccd6b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Viral - cerebrospinal fluid</topic><topic>Antigens</topic><topic>Anxiety - etiology</topic><topic>Anxiety - psychology</topic><topic>Autoantibodies</topic><topic>Autoantibodies - cerebrospinal fluid</topic><topic>Autoimmunity</topic><topic>Brief Report</topic><topic>Cerebrospinal fluid</topic><topic>Children</topic><topic>Comments</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - complications</topic><topic>COVID-19 - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Immunotherapy</topic><topic>Infections</topic><topic>Male</topic><topic>Marijuana Smoking - immunology</topic><topic>Mental disorders</topic><topic>Mental Disorders - cerebrospinal fluid</topic><topic>Mental Disorders - etiology</topic><topic>Mice</topic><topic>Movement Disorders - etiology</topic><topic>Nervous System Diseases - cerebrospinal fluid</topic><topic>Nervous System Diseases - etiology</topic><topic>Neurologic Examination</topic><topic>Neurology</topic><topic>Online First</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Polymerase chain reaction</topic><topic>Psychosis</topic><topic>RNA-directed DNA polymerase</topic><topic>Serology</topic><topic>Severe acute respiratory syndrome</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Teenagers</topic><topic>Transcription Factor 4 - immunology</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bartley, Christopher M</creatorcontrib><creatorcontrib>Johns, Claire</creatorcontrib><creatorcontrib>Ngo, Thomas T</creatorcontrib><creatorcontrib>Dandekar, Ravi</creatorcontrib><creatorcontrib>Loudermilk, Rita L</creatorcontrib><creatorcontrib>Alvarenga, Bonny D</creatorcontrib><creatorcontrib>Hawes, Isobel A</creatorcontrib><creatorcontrib>Zamecnik, Colin R</creatorcontrib><creatorcontrib>Zorn, Kelsey C</creatorcontrib><creatorcontrib>Alexander, Jessa R</creatorcontrib><creatorcontrib>Wapniarski, Anne E</creatorcontrib><creatorcontrib>DeRisi, Joseph L</creatorcontrib><creatorcontrib>Francisco, Carla</creatorcontrib><creatorcontrib>Nash, Kendall B</creatorcontrib><creatorcontrib>Wietstock, Sharon O</creatorcontrib><creatorcontrib>Pleasure, Samuel J</creatorcontrib><creatorcontrib>Wilson, Michael R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of neurology (Chicago)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bartley, Christopher M</au><au>Johns, Claire</au><au>Ngo, Thomas T</au><au>Dandekar, Ravi</au><au>Loudermilk, Rita L</au><au>Alvarenga, Bonny D</au><au>Hawes, Isobel A</au><au>Zamecnik, Colin R</au><au>Zorn, Kelsey C</au><au>Alexander, Jessa R</au><au>Wapniarski, Anne E</au><au>DeRisi, Joseph L</au><au>Francisco, Carla</au><au>Nash, Kendall B</au><au>Wietstock, Sharon O</au><au>Pleasure, Samuel J</au><au>Wilson, Michael R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti–SARS-CoV-2 and Autoantibody Profiles in the Cerebrospinal Fluid of 3 Teenaged Patients With COVID-19 and Subacute Neuropsychiatric Symptoms</atitle><jtitle>Archives of neurology (Chicago)</jtitle><addtitle>JAMA Neurol</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>78</volume><issue>12</issue><spage>1503</spage><epage>1509</epage><pages>1503-1509</pages><issn>2168-6149</issn><eissn>2168-6157</eissn><abstract>IMPORTANCE: Neuropsychiatric manifestations of COVID-19 have been reported in the pediatric population. OBJECTIVE: To determine whether anti–SARS-CoV-2 and autoreactive antibodies are present in the cerebrospinal fluid (CSF) of pediatric patients with COVID-19 and subacute neuropsychiatric dysfunction. DESIGN, SETTING, AND PARTICIPANTS: This case series includes 3 patients with recent SARS-CoV-2 infection as confirmed by reverse transcriptase–polymerase chain reaction or IgG serology with recent exposure history who were hospitalized at the University of California, San Francisco Benioff Children’s Hospital and for whom a neurology consultation was requested over a 5-month period in 2020. During this period, 18 total children were hospitalized and tested positive for acute SARS-CoV-2 infection by reverse transcriptase–polymerase chain reaction or rapid antigen test. MAIN OUTCOMES AND MEASURES: Detection and characterization of CSF anti–SARS-CoV-2 IgG and antineural antibodies. RESULTS: Of 3 included teenaged patients, 2 patients had intrathecal anti–SARS-CoV-2 antibodies. CSF IgG from these 2 patients also indicated antineural autoantibodies on anatomic immunostaining. Autoantibodies targeting transcription factor 4 (TCF4) in 1 patient who appeared to have a robust response to immunotherapy were also validated. CONCLUSIONS AND RELEVANCE: Pediatric patients with COVID-19 and prominent subacute neuropsychiatric symptoms, ranging from severe anxiety to delusional psychosis, may have anti–SARS-CoV-2 and antineural antibodies in their CSF and may respond to immunotherapy.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>34694339</pmid><doi>10.1001/jamaneurol.2021.3821</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2168-6149 |
| ispartof | Archives of neurology (Chicago), 2021-12, Vol.78 (12), p.1503-1509 |
| issn | 2168-6149 2168-6157 |
| language | eng |
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| source | MEDLINE; American Medical Association Journals |
| subjects | Adolescent Animals Antibodies Antibodies, Viral - cerebrospinal fluid Antigens Anxiety - etiology Anxiety - psychology Autoantibodies Autoantibodies - cerebrospinal fluid Autoimmunity Brief Report Cerebrospinal fluid Children Comments Coronaviruses COVID-19 COVID-19 - complications COVID-19 - immunology Female Humans Immunoglobulin G Immunotherapy Infections Male Marijuana Smoking - immunology Mental disorders Mental Disorders - cerebrospinal fluid Mental Disorders - etiology Mice Movement Disorders - etiology Nervous System Diseases - cerebrospinal fluid Nervous System Diseases - etiology Neurologic Examination Neurology Online First Patients Pediatrics Polymerase chain reaction Psychosis RNA-directed DNA polymerase Serology Severe acute respiratory syndrome Severe acute respiratory syndrome coronavirus 2 Teenagers Transcription Factor 4 - immunology Viral diseases |
| title | Anti–SARS-CoV-2 and Autoantibody Profiles in the Cerebrospinal Fluid of 3 Teenaged Patients With COVID-19 and Subacute Neuropsychiatric Symptoms |
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