Anti-Spike IgG in multiple sclerosis patients after BNT162b2 vaccine: An exploratory case-control study in Italy

Abstract

Background: Patients with neuroimmunological conditions such as multiple sclerosis (MS) often receive diseasemodifying therapies (DMTs) or immunosuppressants which may reduce the response to vaccines. BNT162b2 (Pfizer-BioNTech) is the first COVID-19 vaccine authorized in Italy. Its clinical efficacy and serological response were not evaluated in MS patients receiving DMTs or immunosuppressants. This early multicenter study evaluated serological response to BNT162b2 and safety in these patients. Methods: From February 2021 we enrolled consecutive MS patients, treated with at least one DMT and all healthcare workers (HCWs), having received or being scheduled to receive the first dose of BNT162b2. Blood samples were collected after the second vaccine dose and analyzed to quantitatively detect the presence of anti-Spike antibodies. Serological response was compared to the one from a control population of HCWs, with neither neuroimmunological conditions nor receiving immunosuppressants. Patients receiving treatments associated with a possible reduced response (Under-scrutiny treatment group) were also compared to those undergoing other treatments. Anti-Spike levels were described as median and interquartile range (IQR). Comparisons were performed with Wilcoxon-Mann-Whitney test. Solicited and unsolicited adverse events (AEs) were collected. Results: 39 MS patients and a control population of 273 HCWs were included. One patient, under treatment with ocrelizumab, did not respond to BNT162b2, while all the remaining patients and all controls developed a serological response to the vaccine. Median anti-Spike levels were similar between patients (1471.0 BAU/ml; IQR 779.7 to 2357.0) and controls (1479.0 BAU/ml; IQR 813.1 to 2528.0) (p = 0.53). Patients included in the Underscrutiny treatments group showed reduced anti-Spike levels (156.4 BAU/ml; IQR 33.4 to 559.1) compared to those receiving other treatments (1582.4 BAU/ml; IQR 1296.5 to 2219.0) (p = 0.001). Solicited AEs were all mild to moderate in severity, generally reported in the first days after vaccination, and resolved in the following days. Two MS patients reported a clinical relapse after the second vaccine dose. Conclusion: BNT162b2 induced a serological response in MS patients treated with DMTs similar to controls not receiving DMTs or immunosuppressants. Some treatments were associated with reduced levels of anti-Spike antibodies in patients. These observations have relevant implications for treated patients receiving BNT162b2 and the community.

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: a practical review and meta-analysis

“…Based on evidence with moderate certainty, interferons (IFNs) do not decrease the odds of seroconversion (OR (95% CI): 0.84 (0.38 to 1.83), p=0.66) (online supplemental figure 1). All pwMS on IFN in four studies10–13 seroconverted; they showed similar postvaccination antibody concentrations with the UX people, except in one study, in which they showed significantly higher concentrations of anti-Spike (S) receptor binding domain IgG compared with healthy controls 13. The authors suggested that IFN-beta 1 a therapy may promote the postvaccination antibody responses in pwMS, however, this finding was not observed in other studies.…”

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

“…2] [Table 2] (Supplementary Figure 1). No seronegative pwMS on IFN were present in four studies [16][17][18][19] . Quantitative analysis in studies also did not suggest lower concentrations of antibodies among these pwMS postvaccination.…”

“…Moderate-certainty evidence did not suggest any decrease in odds of post-vaccination seroconversion among pwMS on DMF compared to UX people (OR [95%CI]: 1.98 [0.96, 4.09], P=0.07) (Supplementary Figure 3). Seven studies 16,18,19,22,23,25,26 did not contain any seronegative pwMS on DMF following mRNA or inactivated vaccination; Quantitative analysis suggested no difference in post-vaccination antibody concentrations compared to UX people.…”

“…Due to low number of mRNA vaccine studies with measurable relative effect and therefore, the uncertainty of their pooled measures, the difference between the inactivated and mRNA measures did not reach statistical significance (Chi 2 =2.91, P=0.09). Nevertheless, considering that none of the TERI-treated pwMS in any of the studies 16,18,22,[25][26][27][28] remained seronegative after mRNA vaccination, the suggested blunt caused by TERI may not be generalizable to the mRNA-vaccinated pwMS. Furthermore, lower antibody concentrations compared to UX people were observed in pwMS on TERI homogenously in all studies regardless of the used vaccine, but reached statistical significance only in one 28 .…”

“…Moderate-certainty evidence did not suggest any decrease in odds of post-vaccination seroconversion among pwMS on DMF compared to UX people (OR [95%CI]: 1.98 [0.96, 4.09], P=0.07) (Supplementary Figure 3). Seven studies 16,18,19,22,23,25,26 4). Due to low number of mRNA vaccine studies with measurable relative effect and therefore, the uncertainty of their pooled measures, the difference between the inactivated and mRNA measures did not reach statistical significance (Chi 2 =2.91, P=0.09).…”