Table 6.
Studies exploring safety and efficacy of vaccination against COVID-19 in MS patients
| Authors, year, country | Study design | Included patients | Outcomes | Safety results | Efficacy results |
|---|---|---|---|---|---|
| Konig et al., 2021, Norway [6] | Prospective, observational, multicenter | 130 MS patients | Antibody response after third dose of COVID-19 vaccines in antiCD20 and fingolimod-treated patients | Adverse effects were observed in 63.4% MS patients treated with antiCD20 and 37.9% patients treated with fingolimod. Patients who reported AEs had higher lymphocyte counts compared to those who did not (1410 vs 1183, p = 0.003) | Increasing in Ab titer after third dose in both antiCD20 and fingolimod groups (8.9 vs 49.4 in antiCD20 and 9.2 vs 25.1 in the fingolimod group, p < 0.001) |
| Achtnichts et al., 2021, Switzerland [7] | Cross-sectional, observational, monocentric | 16 MS patients | Seroconversion after the third mRNA SARS-CoV-2 vaccine in B cell-depleted pwMS with limited or no IgG response after the standard immunization | Not assessed | After the third vaccination, one out of 16 patients showed an IgG titer deemed clinically relevant. Only the seroconverted patient had measurable B-cell counts at the time of the third vaccination |
| Giossi R. et al., 2021, Italy [8] | Case–control, prospective, multicenter | 39 MS patients, 273 healthcare workers (HCWs) | Serological response in MS patients compared to the one from a control population of HCWs; response in patients receiving treatments associated with possible reduced immune response vs other treatments | 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 | 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 under scrutiny 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) |
| Ciampi E. et al., 2022, Chile [9] | Prospective observational, multicenter | 178 MS patients | Safety and humoral response of inactivated virus and mRNA vaccines against SARS-CoV-2 in patients with MS | The most frequent AE was local pain (14%), with 4 (2.2%) patients experiencing mild-moderate relapses within 8 weeks of first vaccination compared to 11 relapses (6.2%) within the 8 weeks before vaccination (chi-squared 3.41, p = 0.06) | Overall humoral response was observed in 66.9% (62.6% inactivated vs 78.4% mRNA, p = 0.04). In the multivariate analysis including antiCD20 patients, the predictors for a positive humoral response were receiving the mRNA vaccine (OR 8.11 (1.79–36.8), p = 0.007) and a lower number of total infusions (OR 0.44 (0.27–0.74) p = 0.002) |
| Conte W.L., USA [10] | Case–control, observational, single-center | 67 MS patients | Antibody response in patients treated with AntiCD20 and S1p modulators vs other treatments | Not assessed | Patients who received OCR or OFA had decreased odds of forming antibodies (OR 0.031, p < 0.001, 95% CI (0.003–0.268)). Patients who received S1P modulators did not have decreased odds of forming antibodies (OR 0.413, p = 0.413, 95% CI (0.28–21.7)). However, when analyzing the antibody response as a continuous variable, patients on S1P modulators showed lower absolute levels of antibodies (p = 0.024) |
| Katz J.D. et al., 2021, USA [11] | Prospective observational, single-center | 48 MS patients | Humoral response to SARS-CoV-2 vaccines in adult MS patients treated with OCR, using NTZ as a real-world comparator. T-cell response for those OCR-treated patients who did not produce detectable antibodies | Not assessed | Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (p = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses |
| Brill L. et al., 2021, Israel [12] | Prospective observational, single-center | 67 MS patients, 30 HCs | Antibody response in patients treated with cladribine vs HCs | Not assessed | MS patients treated with cladribine (n = 32) had 100% positive serology response against the SARS-CoV-2 spike protein following the second vaccine dose (mean S1/S2-IgG and RBD-IgG: 284.5 ± 104.9, 13,041 ± 9411 AU/mL and 226.3 ± 121.4, 10,554 ± 11,405 AU/mL, respectively |
| Mariottini A. et al., 2021, Italy [18] | Retrospective, observational, single-center | 120 MS patients | Antibody response after vaccination for SARS-CoV-2 | Adverse effects were observed in roughly of patients. 2 patients experienced a clinical relapse | Anti-Spike IgG antibodies were detectable in 85%, being the proportion lower in patients receiving antiCD20 antibodies (45%) compared to non-depletive treatments (99%), p < 0.0001 |
| Pitzalis M. et al., 2021, Italy [14] | Prospective, observational, single-center | 912 MS patients and 63 healthy controls | Antibody response 30 days after the second dose of BNT162b2 vaccine | Not analyzed | Absence of significant difference between untreated MS patients and healthy control in anti-S antibodies response (p = 0.51); significantly lower level of anti-S antibodies production in MS patients treated with teriflunomide (IRR = 0.51, p = 1.44E-05), azathioprine (IRR = 0.37, p = 3.26E-06), natalizumab (IRR = 0.72, p = 0.034), fingolimod (IRR = 0.13, p = 1.89E-39), ocrelizumab (IRR = 0.10, p = 4.88E-38), and rituximab (IRR = 0.22, p = 8.36E-07) compared to untreated patients; reduced levels of antibodies in older (IRR = 0.98, p = 3.85E-03), male individuals (IRR = 0.83, p = 0.021) or reduced EDDS (IRR = 0,93, p = 1.31E-04) |
| Räuber S. et al., 2021, Germany [15] | Retrospective, observational, single-center | 59 OCR-treated patients with MS | Anti-SARS-CoV-2-antibody titers and SARS-CoV-2-specific T-cell response | 92.7% reported mild side effects of vaccination | Anti-SARS-CoV-2(S) antibodies were found in 27.1% and SARS-CoV-2-specific T-cell response in 92.7% of cases |
| Achiron A. et al., 2021, Israel [3] | Observational, single-center | 555 MS patients who received the first dose of BNT162b2 vaccine and 435 who received the second dose | Characterize safety and occurrence of immediate relapses following COVID-19 vaccination | 29.7% reported side effects after the first dose and 40.2% after the second, 16% and 14.2% had local AEs after the first and second dose, respectively, fever and flu-like symptoms were reported by 2% and 11.9% of patients | Not analyzed |
| Achiron A. et al., 2021, Israel [16] | Observational, single-center | 125 MS patients | Antibody response 30 days after the second dose of BNT162b2 vaccine | Not analyzed | Protective humoral immunity was observed in 97.9% of healthy subjects, 100% of untreated MS patients, 100% of MS patients treated with cladribine, 22.7% of patients treated with ocrelizumab, and 3.8% of those treated with fingolimod |
| Sokratis A. et al., 2021, USA [17] | Observational, single-center | 20 patients with MS on antiCD20 antibody monotherapy and 10 healthy controls | Antigen-specific antibody, B cell, and T-cell responses | Not analyzed | Eighty-nine percent of patients developed detectable anti-Spike IgG and only 50% mounted detectable anti-RBD IgG responses by T5. All patients generated antigen-specific CD4 and CD8 T-cell responses after vaccination |
| Katz et al., 2022, USA [35] | Prospective, observational, single-center | 48 patients with MS treated with OCR (n = 33) or NTZ (n = 15) | Antigen-specific antibodies, T-cell responses | Not analyzed | Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (p = 0.062) |