tetano
Editor, Senior Moderator
Ther Adv Infect Dis
. 2025 Sep 9:12:20499361251370471.
doi: 10.1177/20499361251370471. eCollection 2025 Jan-Dec. 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
M Hema Prashaad[SUP] 1 [/SUP], Rachel Wan En Siew[SUP] 2 [/SUP], Amelia Yun Yi Aw[SUP] 2 [/SUP], Janice Hui Yi Tan[SUP] 3 [/SUP], Muhammad Yaaseen Gulam Mohamed[SUP] 4 [/SUP], Janis Tye Siew Noi[SUP] 2 [/SUP], Kalpana Prasad[SUP] 2 [/SUP], Kevin Tan[SUP] 1 2 [/SUP], Jens Kuhle[SUP] 5 [/SUP], Yinxia Chao[SUP] 1 4 [/SUP], Ivy Ai-Wei Ho[SUP] 1 3 [/SUP], Tianrong Yeo[SUP] 6 1 7 [/SUP]
Affiliations
Background: 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.
Objectives: 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.
Design: A prospective observational study conducted at National Neuroscience Institute, Singapore.
Methods: 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).
Results: 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.
Conclusion: 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.
Keywords: COVID-19; SARS-CoV-2; multiple sclerosis; neuroimmunological diseases; vaccine.
. 2025 Sep 9:12:20499361251370471.
doi: 10.1177/20499361251370471. eCollection 2025 Jan-Dec. 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
M Hema Prashaad[SUP] 1 [/SUP], Rachel Wan En Siew[SUP] 2 [/SUP], Amelia Yun Yi Aw[SUP] 2 [/SUP], Janice Hui Yi Tan[SUP] 3 [/SUP], Muhammad Yaaseen Gulam Mohamed[SUP] 4 [/SUP], Janis Tye Siew Noi[SUP] 2 [/SUP], Kalpana Prasad[SUP] 2 [/SUP], Kevin Tan[SUP] 1 2 [/SUP], Jens Kuhle[SUP] 5 [/SUP], Yinxia Chao[SUP] 1 4 [/SUP], Ivy Ai-Wei Ho[SUP] 1 3 [/SUP], Tianrong Yeo[SUP] 6 1 7 [/SUP]
Affiliations
- PMID: 40937008
- PMCID: PMC12420963
- DOI: 10.1177/20499361251370471
Background: 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.
Objectives: 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.
Design: A prospective observational study conducted at National Neuroscience Institute, Singapore.
Methods: 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).
Results: 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.
Conclusion: 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.
Keywords: COVID-19; SARS-CoV-2; multiple sclerosis; neuroimmunological diseases; vaccine.