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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Kevin Tan has received travel grants and compensation from Novartis, Merck, Sanofi, Eisai, Roche, and Terumo BCT for consulting services and education activities. Tianrong Yeo has received honoraria from ASNA, Edanz Pharma, Euroimmun AG, Merck, Novartis, Roche, Terumo BCT for consulting services and speaker’s fees, and research grants from the National Medical Research Council (Singapore), AstraZeneca and Roche. He has also received travel grants and awards from PACTRIMS, ACTRIMS, ECTRIMS, Orebro University, UCB and Merck. The other authors declare no competing interests.
