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Introduction: In patients with Multiple Sclerosis (pwMS), specific disease modifying treatments (DMTs) may compromise immune response following SARS-CoV-2 vaccination. Limited information is available, whether levels of anti-SARS-CoV-2 antibodies are linked to the risk of breakthrough infections in pwMS. Objective(s): To determine the rate of Omicron breakthrough infection and severity of COVID-19 in a cohort of MS patients treated with different DMTs and to estimate the impact of SARSCoV- 2-specific antibody level on breakthrough infection risk. Method(s): This study is nested within the Swiss MS Cohort, a nationwide multicenter study that has recruited 1585 pwMS. Patients who received two doses of SARS-CoV-2 vaccines before Omicron became the dominant variant in Switzerland on Dec-15, 2021 and had a follow-up thereafter were included. Data on SARS-CoV-2 infections, severity of COVID-19 according to the WHO scale and SARS-CoV-2 vaccines were collected by questionnaires. Anti-SARS-CoV-2-S antibody levels were measured after the second vaccine dose. Incidence of infections grouped by antibody level after second vaccination was visualized using Kaplan-Meier curves. Cox regression models were used to estimate the impact of antibody levels on the hazard of breakthrough infection during follow-up. Result(s): 242 pwMS (median age 49y [39,58], 162 (67%) female, 36 (15%) with progressive disease, median EDSS 2.5 [1.5,4.0]) were included. 22 (9%) had SARS-CoV-2 infection and 137 (57%) at least one additional vaccine dose prior to Omicron start. Since then, 57 breakthrough infections were reported. Severity of breakthrough disease on WHO scale ranged from 1-10: 7 were asymptomatic, 46 were symptomatic as outpatients, 3 were hospitalized and 1 died. Patients with antibody levels >150U/ml (n = 95, 39%) after second vaccination had a 64% reduced risk for Omicron breakthrough-infection compared to patients with antibody levels <0.7U/ml (n = 81, 33%) (HR 0.36, 95%CI=0.18- 0.71, p<0.01). This effect was maintained after adjustment for DMT at vaccination and time since second vaccination Conclusion(s): Humoral immune response after second SARSCoV- 2 vaccination is associated with Omicron breakthrough infection rate, a finding contrasting general populations, where antibody levels seem to have little impact on protecting from Omicron infection. Most breakthrough infections in our cohort were mild. Analyses on the effect of booster vaccinations on serology and infection rates will follow.
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Introduction: Some disease modifying treatments (DMTs) impair response to SARS-CoV-2 vaccines in multiple sclerosis (MS), potentially increasing the risk of breakthrough infections. Objective(s): To investigate longitudinal post-vaccine antibody dynamics and memory B cell responses after 2 and 3 SARSCoV- 2 mRNA vaccine doses, and their association with risk of COVID-19 in MS patients treated with different DMTs. Method(s): Prospective observational monocenter cohort study in MS patients undergoing SARS-CoV-2 mRNA vaccinations. Anti- SARS-CoV-2 spike IgG serum titers were measured by chemiluminescence microparticle immunoassay. Frequency of spike-specific memory B cells were measured upon polyclonal stimulation of total PBMCs and screening of secreted antibodies by ELISA. Result(s): We recruited 120 MS patients (58 on anti-CD20, 9 on S1P-modulators, 15 on cladribine, 24 on teriflunomide and 14 untreated) and collected 392 samples before and up to 10.8 months after a 2nd vaccine dose. Compared to no treatment, anti-CD20 antibodies (beta=-2.07, p<0.001) and S1P-modulators (beta=-2.02, p<0.001) were associated with lower anti-spike IgG titers, while teriflunomide and cladribine were not. Anti-spike IgG titers progressively decreased with months since last vaccine dose (beta=-0.14, p<0.001), independently of DMTs. Within anti-CD20 treated patients, anti-spike IgG remained constantly higher in those with greater baseline CD19+ B cell counts and were not influenced by post-vaccine anti-CD20 infusions. Antispike IgG titers increased after a 3rd vaccine dose on cladribine and teriflunomide and marginally on anti-CD20 and S1Pmodulators. Spike-specific memory B cell responses were weaker on S1P-modulators and anti-CD20 than on teriflunomide and influenced by post-vaccine anti-CD20 infusions. Risk of SARS-CoV-2 infection was predicted by SARS-CoV-2 IgG at last sample before infection (OR=0.56, 95%CI=0.37-0.86, p=0.008). Conclusion(s): Post-vaccine SARS-CoV-2 IgG antibody titers progressively decrease over time in MS regardless of DMTs, and are associated with risk of breakthrough COVID-19. Both immediate humoral and specific memory B cell responses are diminished in patients on S1P-modulator and anti-CD20 antibody treatments. Within the latter group, B cell count at first vaccine dose determines anti-spike IgG production shortly after vaccination, whereas post-vaccine anti-CD20 infusions negatively impact memory B cell responses.
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Introduction: Recently developed vaccines can prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but vaccine-induced immune responses can be impaired by disease modifying treatments (DMTs) commonly used in multiple sclerosis (MS). Objectives: To investigate the humoral response to SARS-CoV-2 mRNA vaccines in MS patients under different DMTs, and provide indications on potential strategies to optimize SARS-CoV-2 vaccination. Methods: this was a prospective single center observational cohort study performed at the Neurocenter of Southern Switzerland (Lugano Switzerland). MS patients were consecutively recruited between 25/02/2021 and 16/04/2021 during routine clinical visits. Inclusion criteria were: A diagnosis of MS according to the 2017 McDonald criteria;age >18 years;scheduled mRNA COVID-19 vaccination. IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured by chemiluminescence microparticle immunoassay (CMIA) at 21-35 days after the second vaccine dose. Results: A total of 107 patients were included (56 under anti-CD20 therapy, 14 under cladribine, 20 under teriflunomide, 7 under sphingosine- 1-phosphate receptor [S1P] modulators, and 10 untreated). Post-vaccine SARS-CoV-2 IgG titers were high among untreated patients (median=8,003 [QR=1,792-21,137] mAU/ml), patients under treatment with cladribine (6,175 [IQR=3,982-10,194] mAU/ ml), and teriflunomide (5,630 [2,596-14,087] mAU/ml). Titers were significantly lower under anti-CD20 therapy (68 [0-808] mAU/ml;β=-2.009, p<0.001) and S1P modulators (123 [57-641)] mAU/ml;β=-1.512, p=0.026). Within patients under anti-CD20 therapy, postvaccine SARS-CoV-2 IgG titers were increased in those who had their last anti-CD20 infusion >6 months before vaccination, and with higher CD19+ B cell counts at vaccination. Conclusions: The humoral response to SARS-CoV-2 mRNA vaccines is preserved in untreated MS patients and those treated with cladribine and teriflunomide, but reduced under anti-CD20 therapies and S1P-modulators. Within patients under treatment with anti-CD20 therapies, delaying vaccinations to more than 6 months after last infusion and waiting for B cell repopulation are potential strategies to optimize humoral response to vaccines.
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Background: COVID-19 disease course in MS has been described in various cohorts. Limited data is available on humoral immune responses following SARS-CoV-2 infection and vaccination. Objectives: To determine the rate of confirmed SARS-CoV-2 infection and severity of COVID-19 in a cohort of MS patients and to quantify SARS-CoV-2-specific antibody response. Methods: The study is nested within the Swiss MS Cohort, a nationwide multicenter study that has recruited 1504 persons with MS (pwMS) since 2012. PCR-confirmed SARS-CoV-2 infections, severity of COVID-19 according to the WHO clinical progression scale and immunizations with SARS-CoV-2 vaccines were captured by questionnaires used for interviews every 6 or 12 months. Anti-SARS-CoV-2 spike protein and nucleocapsid antibody levels will be determined by electrochemiluminescence immunoassay (ECLIA) (Elecsys, Anti-SARS-CoV-2, Roche Diagnostics) in sera of all participants. Results: Between February 2021 and April 2021, study questionnaires were completed for 253 pwMS (median age 47 years, 162 female). 211 pwMS (83%) had a relapsing, 25 (10%) a secondary progressive, 13 (5%) a primary progressive disease course and 4 (2%) a clinically isolated syndrome. Median disease duration was 12 years and median EDSS was 2.5. 218 (86%) pwMS were treated with DMTs: Ocrelizumab (27%), fingolimod (26%), dimethyl fumarate (15%), rituximab (10%), natalizumab (9%), other DMTs (13%). 15 (5.9%) of 253 pwMS had a positive SARSCoV- 2 PCR test since March 2020. In these pwMS, COVID-19 severity ranged from 1-10 on the WHO clinical progression scale: 1 pwMS was asymptomatic, 10 pwMS were symptomatic as outpatients (8 independently, 2 needed assistance), 3 pwMS were hospitalized (1 without oxygen therapy, 2 with oxygen by mask or nasal prongs) and 1 pwMS died. By April 2021, 24 and 38 pwMS received one and two doses of SARS-CoV-2 mRNA vaccines, respectively. Conclusions and outlook: Since start of the pandemic, rate of PCR-confirmed SARS-CoV-2 infection in our sample was slightly lower compared to incidence of laboratory-confirmed cases in Switzerland. The majority of pwMS had mild COVID-19. The study will continue until 2024 and by ECTRIMS 2021, we anticipate a doubling of completed questionnaires and to report preliminary results of serological measurements. This will allow us to present vaccine- and natural infection induced serological anti-SARS-CoV-2 responses in pwMS and assess differences related to various DMTs or COVID-19 severity.