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Analysis of institutional authors

Guasp MAuthorMartinez-Hernandez EAuthorSantana DAuthorSaiz AAuthorBalasa MAuthorRuiz-García RCorresponding AuthorSanchez-Valle RCorresponding Author

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CSF Biomarkers in COVID-19 Associated Encephalopathy and Encephalitis Predict Long-Term Outcome

Publicated to:Frontiers In Immunology. 13 866153- - 2022-04-11 13(), DOI: 10.3389/fimmu.2022.866153

Authors: Guasp, Mar; Munoz-Sanchez, Guillermo; Martinez-Hernandez, Eugenia; Santana, Daniel; Carbayo, Alvaro; Naranjo, Laura; Bolos, Uma; Saiz, Albert; Balasa, Mircea; Ruiz-Garcia, Raquel; Sanchez-Valle, Raquel

Affiliations

Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain - Author
Hosp Clin Barcelona, Ctr Diagnost Biomed, Immunol Dept, Barcelona, Spain - Author
Hosp Clin Barcelona, Neurol Serv, Barcelona, Spain - Author
Hosp Univ Bellvitge, Dept Immunol, L'Hospitalet De Llobregat, Barcelona, Spain - Author
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Neuroimmunol Program, Barcelona, Spain - Author
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Barcelona, Spain - Author
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Abstract

Patients with coronavirus disease 2019 (COVID-19) frequently develop acute encephalopathy and encephalitis, but whether these complications are the result from viral-induced cytokine storm syndrome or anti-neural autoimmunity is still unclear. In this study, we aimed to evaluate the diagnostic and prognostic role of CSF and serum biomarkers of inflammation (a wide array of cytokines, antibodies against neural antigens, and IgG oligoclonal bands), and neuroaxonal damage (14-3-3 protein and neurofilament light [NfL]) in patients with acute COVID-19 and associated neurologic manifestations (neuro-COVID). We prospectively included 60 hospitalized neuro-COVID patients, 25 (42%) of them with encephalopathy and 14 (23%) with encephalitis, and followed them for 18 months. We found that, compared to healthy controls (HC), neuro-COVID patients presented elevated levels of IL-18, IL-6, and IL-8 in both serum and CSF. MCP1 was elevated only in CSF, while IL-10, IL-1RA, IP-10, MIG and NfL were increased only in serum. Patients with COVID-associated encephalitis or encephalopathy had distinct serum and CSF cytokine profiles compared with HC, but no differences were found when both clinical groups were compared to each other. Antibodies against neural antigens were negative in both groups. While the levels of neuroaxonal damage markers, 14-3-3 and NfL, and the proinflammatory cytokines IL-18, IL-1RA and IL-8 significantly associated with acute COVID-19 severity, only the levels of 14-3-3 and NfL in CSF significantly correlated with the degree of neurologic disability in the daily activities at 18 months follow-up. Thus, the inflammatory process promoted by SARS-CoV-2 infection might include blood-brain barrier disruption in patients with neurological involvement. In conclusion, the fact that the levels of pro-inflammatory cytokines do not predict the long-term functional outcome suggests that the prognosis is more related to neuronal damage than to the acute neuroinflammatory process.Copyright © 2022 Guasp, Muñoz-Sánchez, Martínez-Hernández, Santana, Carbayo, Naranjo, Bolós, Framil, Saiz, Balasa, Ruiz-García, Sánchez-Valle and The Barcelona Neuro-COVID Study Group.

Keywords

cytokine stormencephalitisencephalopathyinflammatory cytokinesneuro-covidneurofilamentsneuronal antibodiessars-cov-2AdultArticleBiological markerBiomarkersBrain diseaseCerebrospinal fluidCitocinesComplicationCoronavirus disease 2019Coronavirus infectionsCovid-19CytokineCytokinesElectroencephalogramEncephalitisEncephalopathyEpilepsyFemaleFractalkineGamma interferonGranulocyte colony stimulating factorHumanHumansInflammatory cytokinesInterleukin 1 receptor antagonist proteinInterleukin 1 receptor blocking agentInterleukin 18Interleukin 1betaInterleukin 6Interleukin 8Interleukin-18Interleukin-8Major clinical studyMaleMonocyte chemotactic protein 1Nasopharyngeal swabNeuro-covidNeurofilamentsNeuronal antibodiesNuclear magnetic resonance imagingOutcome assessmentReverse transcription polymerase chain reactionSars-cov-2Tumor necrosis factor

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Frontiers In Immunology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 35/161, thus managing to position itself as a Q1 (Primer Cuartil), in the category Immunology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 6.17. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 5.43 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 44.34 (source consulted: Dimensions Jun 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-06-23, the following number of citations:

  • WoS: 72
  • Scopus: 75
  • Europe PMC: 61
  • OpenCitations: 68

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-06-23:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 75.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 75 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 20.45.
  • The number of mentions on the social network X (formerly Twitter): 31 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/2445/209137

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Guasp Verdaguer, Mar) and Last Author (Sanchez del Valle Díaz, Raquel).

the authors responsible for correspondence tasks have been Ruiz García, Raquel and Sanchez del Valle Díaz, Raquel.