{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:34:50Z","timestamp":1777880090223,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001350","name":"Singapore Ministry of Health","doi-asserted-by":"crossref","award":["National Medical Research Council Clinician Scient"],"award-info":[{"award-number":["National Medical Research Council Clinician Scient"]}],"id":[{"id":"10.13039\/501100001350","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Neuroscience Institute","award":["Neuroimmunology Academic Fund"],"award-info":[{"award-number":["Neuroimmunology Academic Fund"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Infection"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Immunosuppressive treatment can attenuate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses. Moreover, SARS-CoV-2 has neuroinvasive potential and may induce a persistent pro-inflammatory milieu following infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To investigate if diminished post-vaccine humoral responses can be overcome with additional vaccine doses and\/or breakthrough COVID-19 infections, and if COVID-19 infection can lead to a pro-inflammatory state with neuroaxonal\/neuroglial injury in the intermediate-term in patients with central nervous system (CNS) neuroimmunological diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A prospective observational study conducted at National Neuroscience Institute, Singapore.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Serum levels of SARS-CoV-2 neutralising antibodies (NAbs) were measured in patients with CNS neuroimmunological diseases following their fourth SARS-CoV-2 mRNA vaccine (V4), or after breakthrough COVID-19 infection following three prior SARS-CoV-2 mRNA vaccinations, or both. Serum levels of pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF) were evaluated post-COVID-19 infection and post-V4, compared to baseline within individuals. Serum neurofilament-light chain (NfL) and glial fibrillary acidic protein (GFAP), biomarkers of neuroaxonal and astroglial injury, respectively, were measured at baseline and post-COVID-19 infection within patients with relapsing-remitting multiple sclerosis (RRMS) and neuromyelitis optica spectrum disorder (NMOSD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Sixty-one patients with various CNS neuroimmunological diseases were recruited, including 34 with MS and 19 with NMOSD. All had received at least three doses of the SARS-CoV-2 mRNA vaccine. Patients on anti-CD20\/sphingosine-1-phosphate-receptor modulators (S1PRM) showed significantly reduced NAbs levels in both post-V4 and post-COVID-19 infection scenarios, compared to patients on other immunotherapies. No significant differences between baseline and post-COVID-19 infection concentrations of IL-6 and TNF were observed. Within RRMS and NMOSD patients, NfL and GFAP levels remained similar between baseline and post-COVID-19 infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Anti-CD20\/S1PRM treatments are associated with persistently diminished humoral responses post-V4\/infection. Patients with CNS neuroimmunological diseases do not show biomarker evidence of intermediate-term pro-inflammatory states and neural injury after COVID-19 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/20499361251370471","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T12:04:13Z","timestamp":1757419453000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal quantification of serum SARS-CoV-2 neutralising antibodies, pro-inflammatory cytokines, NfL and GFAP before and after breakthrough COVID-19 infection in CNS neuroimmunological diseases: a prospective observational study"],"prefix":"10.1177","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7452-6626","authenticated-orcid":false,"given":"M.","family":"Hema Prashaad","sequence":"first","affiliation":[{"name":"Duke-NUS Medical School, Singapore, 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