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.

Keywords: BNT162b2 messenger RNA (mRNA); COVID-19; COVID-19 vaccination; SARS-CoV-2; disease-modifying therapy (DMT); humoral immunity; multiple sclerosis; vaccine efficacy and effectiveness.

Figure 1

Timeline of MS patients’ enrollment. Schematic of the vaccination (blue) and sample collection (green) timeline in MS patients.

Figure 2

Post-vaccination SARS-CoV-2 anti-S antibody response by disease- modifying therapy (DMT) in MS patients negative for anti-N antibodies. (A) Antibody response to SARS-CoV-2 vaccination by DMT in MS patients six month after SARS-CoV-2 vaccination (T2). (B) Antibody response one month after booster (T3) by DMT in MS patients. Results are reported as boxplots, showing the median value (in bold) and the quartiles as box limits; whiskers at the top and bottom sides represent the overall maximum value and the overall minimum value, respectively. Data outside boxes and whiskers represent the outliers of the distribution. (**P<0.01; ***<0.001). (UNT, untreated; ALEM, alemtuzumab; IFN, interferon; GA, glatiramer acetate; DMF, dimethyl fumarate; NAT, natalizumab; CLA, cladribine; TER,terifluomide; AZA, azathioprine; FTY, fingolimod; RTX, rituximab; OCR, ocrelizumab).

Figure 3

Cross-sectional humoral response over time (T1, T2 and T3) in all the MS patients treated with different DMTs or untreated. Post-vaccination anti-S antibody response by disease- modifying therapy (DMT) in MS patients. Results are represented as histogram showing the median value. Significance was tested using Mann-Whitney test. (**P<0.01; ***<0.001). (UNT, untreated; ALEM, alemtuzumab; IFN, interferon; GA, glatiramer acetate; DMF, dimethyl fumarate; NAT, natalizumab; CLA,cladribine; TER, terifluomide; AZA, azathioprine; FTY, fingolimod; RTX, rituximab; OCR, ocrelizumab). n.s. indicate not significant.

Figure 4

Longitudinal humoral response over time (T1, T2 and T3) in 94 MS patients treated with different DMTs or untreated and present at each time point. Post-vaccination anti-S antibody response by disease- modifying therapy (DMT) in MS patients is represented longitudinally. Results are represented as histogram showing the median value. (UNT, untreated; ALEM, alemtuzumab; IFN, interferon; GA, glatiramer acetate; DMF, dimethyl fumarate; NAT, natalizumab; CLA, cladribine; TER, terifluomide; AZA, azathioprine; FTY, fingolimod; RTX, rituximab; OCR, ocrelizumab; pz, patients).