Third COVID-19 vaccine dose for people with multiple sclerosis who did not seroconvert following two doses of BBIBP-CorV (Sinopharm) inactivated vaccine: A pilot study on safety and immunogenicity.

Background: People with multiple sclerosis (pwMS) on anti-CD20 therapies (aCD20) and fingolimod have shown inadequate humoral responses to COVID-19 vaccines. Objective: The objective of the study was to pilot larger studies by demonstrating the safety and comparing the immunogenicity of different types of third doses in seronegative pwMS after two doses of BBIBP-CorV inactivated vaccine. Methods: In December 2021, subject to receiving their third dose, being COVID-19-naiive, and receiving no corticosteroid within two months, we measured the level of anti-SARS-CoV-2-Spike IgG in pwMS seronegative after two shots of BBIBP-CorV inactivated vaccine. Results: We included 20/29 pwMS who received adenoviral vector (AV), 7/29 who received inactivated, and 2/29 who received conjugated third doses. No serious adverse events were reported two weeks post-third dose. The pwMS receiving AV third doses showed significantly increased IgG concentrations, while only the ones not on aCD20 and fingolimod responded to inactivated third doses. An ordinal logistic multivariable generalized linear model indicated that age (per year ß: -0.10, P = 0.04), type of disease-modifying therapy (aCD20 ß: -8.36, P <0.01; fingolimod ß: -8.63, P = 0.01; others: reference), and type of third dose (AV or conjugated ß: 2.36, P = 0.02; inactivated: reference) are predictive of third dose immunogenicity among pwMS who remain seronegative after two shots of BBIBP-CorV vaccine. Statistical significance was not achieved for variables sex, MS duration, EDSS, duration of DMT, duration of third dose to IgG test, and duration from last aCD20 infusion to third dose. Conclusion: This preliminary pilot study highlights the need for further research to determine the optimal COVID-19 third dose vaccination strategy for pwMS living in areas where BBIBP-CorV vaccine has been used.

SARS-CoV-2 serology among people with multiple sclerosis on disease-modifying therapies after BBIBP-CorV (Sinopharm) inactivated virus vaccination: Same story, different vaccine.

BACKGROUND: Various studies indicated blunted humoral responses to COVID-19 mRNA and viral vector vaccines among people with multiple sclerosis (pwMS) on sphingosine 1-phosphate receptor (S1PR) modulators and anti-CD20 therapies (aCD20); however, limited evidence was found regarding SARS-CoV-2 serology after inactivated virus vaccination. OBJECTIVE: To provide evidence regarding humoral response to COVID-19 inactivated virus vaccination among pwMS on disease-modifying therapies (DMTs). METHODS: A cohort study was carried out in Isfahan, Iran, enrolling DMT-exposed pwMS and unexposed (UX) healthy participants. Post-vaccination anti-SARS-CoV-2 Spike IgG serology testing was carried out among the participants and compared between participants based on their DMT exposure, using proper statistical tests. A multivariable logistic regression model was used to control for confounding. Association between the second vaccine dose-to-phlebotomy (vac2phleb) and the humoral response was investigated in each DMT-exposed cohort, using linear regression. Among the aCD20 cohort, the association of the last aCD20 infusion-to-first vaccine dose period with serostatus was investigated using an unpaired t-test. RESULTS: After enrolling 358 participants (144 pwMS and 214 healthy), blunted humoral responses were only observed in fingolimod (Log10 mean diff. [SE]: 0.72 [0.18], P = 0.001) and aCD20 (Log10 mean diff. [SE]: 0.75 [0.15], P < 0.001) cohorts compared to the UX cohort. Multivariable analysis confirmed the results. The study did not achieve enough statistical power to detect a significant association between the vac2phleb period and humoral responses. The last aCD20 infusion to first vaccination dose period was longer in the seroconverted pwMS on aCD20 (mean diff. [SE]: 8.43 weeks [2.57], P = 0.005). CONCLUSION: The results of this study mirrored the results of previous studies among mRNA- or viral vector-vaccinated pwMS on DMTs. Therefore, it can be concluded that mode of action contributes less than timing, to the efficiency of vaccination strategies among pwMS on DMTs - especially the ones on S1PR modulators and aCD20. Meanwhile, the mentioned pwMS should be advised to receive early boosters and remain vigilant until further data becomes available and more efficient vaccination strategies are crafted.