Changes in COVID-19 antibodies, inflammation markers, and brain injury proteins before and after breakthrough infection in people with central nervous system immune diseases
Sixty-one patients with central nervous system neuroimmunological diseases participated in the study.
Patients on anti-CD20 or sphingosine-1-phosphate-receptor modulators exhibited significantly lower levels of neutralizing antibodies following the fourth vaccine dose and after COVID-19 infection compared to those on other immunotherapies.
No significant changes were observed in the levels of interleukin-6 and tumor necrosis factor between baseline and post-COVID-19 infection.
In patients with relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder, and levels did not differ between baseline and post-COVID-19 infection.
Simplified
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 (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 interleukin-6 (IL-6) and tumour necrosis factor (TNF) were evaluated post-COVID-19 infection and post-V4, compared to baseline within individuals. Serum (NfL) and (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.
Key numbers
2.1%
Decrease in levels post-
Median levels in patients on after .
1.9%
Decrease in levels post-COVID-19 infection
Median levels in patients on after COVID-19 infection.
61 patients
Study population size
Total number of patients included in the analysis.
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