Cross-sectional analysis of the humoral response after SARS-CoV-2 vaccination in Sardinian multiple sclerosis patients, a follow-up study

Abstract

Monitoring immune responses to SARS-CoV-2 vaccination and its clinical efficacy over time in Multiple Sclerosis (MS) patients treated with disease-modifying therapies (DMTs) help to establish the optimal strategies to ensure adequate COVID-19 protection without compromising disease control offered by DMTs. Following our previous observations on the humoral response one month after two doses of BNT162b2 vaccine (T1) in MS patients differently treated, here we present a cross-sectional and longitudinal follow-up analysis six months following vaccination (T2, n=662) and one month following the first booster (T3, n=185). Consistent with results at T1, humoral responses were decreased in MS patients treated with fingolimod and anti-CD20 therapies compared with untreated patients also at the time points considered here (T2 and T3). Interestingly, a strong upregulation one month after the booster was observed in patients under every DMTs analyzed, including those treated with fingolimod and anti-CD20 therapies. Although patients taking these latter therapies had a higher rate of COVID-19 infection five months after the first booster, only mild symptoms that did not require hospitalization were reported for all the DMTs analyzed here. Based on these findings we anticipate that additional vaccine booster shots will likely further improve immune responses and COVID-19 protection in MS patients treated with any DMT.

Long-Term Immune Response Profiles to SARS-CoV-2 Vaccination and Infection in People with Multiple Sclerosis on Anti-CD20 Therapy

“…Our study shows a pronounced impact of COVID-19 infection on antibody and T-cell responses. Both responses were generally higher in patients who had a COVID-19 infection in addition to their vaccinations, which is in line with other published data in anti-CD20-treated patients as well as in the general population [ 11 , 25 , 33 , 34 , 35 ]. However, a few studies did not report a difference in antibody levels upon combined infection and vaccination [ 36 , 37 ].…”

“…In anti-CD20-treated pwMS, there was only a declining trend in antibody titers until six months after primary vaccination that did not reach statistical significance, but booster vaccination also led to significantly higher titers compared to primary vaccination. As reported in other studies, the lack of decline in antibody titers six months after primary vaccination in anti-CD20-treated pwMS was likely due to the initially low titers [3,[23][24][25][26]. Concerning booster vaccination, our data correspond to several other studies showing a significant increase in antibody titers upon booster vaccination in anti-CD20-treated pwMS, though with a less steep increase compared to untreated pwMS [19,21,22,25,27,28].…”

“…As reported in other studies, the lack of decline in antibody titers six months after primary vaccination in anti-CD20-treated pwMS was likely due to the initially low titers [3,[23][24][25][26]. Concerning booster vaccination, our data correspond to several other studies showing a significant increase in antibody titers upon booster vaccination in anti-CD20-treated pwMS, though with a less steep increase compared to untreated pwMS [19,21,22,25,27,28]. In our cohort, 42.3% were seropositive after booster vaccination, corresponding to the range of the previously reported 33.3% and 85% [8,22,24,26,28,29,32].…”

“…While immune responses to primary vaccination are relatively well studied, less is known about the durability of these vaccination responses. Similar to the kinetics of antibodies in the general population, several studies showed a decrease in SARS-CoV-2-specific humoral responses during the six months after initial vaccination in anti-CD20-treated people with MS (pwMS) [ 17 , 18 , 19 , 20 , 21 , 22 ], whereas other studies reported no significant reduction in antibody titers over time, possibly attributable to initially low titers [ 3 , 23 , 24 , 25 , 26 ]. As for virus-specific T-cell responses, two studies reported a decline thereof in the months following primary vaccination [ 16 , 18 ].…”

“…Data on the effect of booster vaccination (third dose) in anti-CD20-treated pwMS are also inconclusive. As for humoral responses, multiple studies demonstrated a significant increase in SARS-CoV-2-specific antibodies after booster vaccination in anti-CD20-treated pwMS, albeit with a less pronounced increment compared to healthy controls or pwMS receiving other DMTs [ 19 , 21 , 22 , 25 , 27 , 28 ]. Contrarily, two studies did not show a significant increase in antibody titers after booster vaccination in ocrelizumab-treated pwMS [ 3 , 29 ].…”