ABSTRACT
Introduction: The new SARS-CoV-2-mRNA-vaccines provide protection against severe COVID-19 infection. Disease modifying therapies (DMTs) for treatment of persons with multiple sclerosis (pwMS) differently impact humoral and cellular immunity and therefore can diminish vaccination outcomes. Thus, it is crucial to investigate the influence of different DMTs on the immune response after SARS-CoV-2 vaccination of pwMS. Objective(s): To investigate antibody and T-cell responses after SARS-CoV-2-vaccination in pwMS treated with different DMTs. Method(s): We studied antibody and T-cell responses in pwMS 4 and 12 weeks after the second dose of mRNA-vaccination against SARS-CoV-2. The results were compared to baseline samples taken before the first dose of SARS-CoV-2-vaccination. We screened and included 148 pwMS treatedwith natalizumab (n=23), dimethylfumarate (n=24), fingolimod (n=39), cladribine (n=31), alemtuzumab (n=17) and teriflunomide (n=14). Healthy controls (HC) (n=43) were used as a comparison. To evaluate humoral immune responses, IgG reactivity was measured towards three different SARS-CoV-2 antigens using a multiplex bead assay: full-length spike glycoprotein (spike S1S2 foldon), spike S1 domain and the nucleocapsid protein C-terminal domain (Nucleocapsid C). Furthermore, the antibody data allowed us to distinguish pwMS who had been vaccinated after a previous SARS-CoV-2-infection. Cellular immune responses were studied using a Fluorospot assay measuring IFNy and IL-13 T-cell responses to the spike S1 domain and Nucleocapsid C. Result(s): Humoral responses to vaccination were comparable between HC and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but suppressed with fingolimod. In addition, T-cell responses were nearly absent in the fingolimod group and moderately reduced in the cladribine group. Conclusion(s): In this comprehensive study of both antibody and cellular responses to SARS-CoV-2-vaccination in pwMS on different DMTs, fingolimod was associated with abrogated responses in both aspects, while cladribine-treated individuals displayed reduced cellular response only. These findings are of relevance for risk mitigation strategies and vaccination recommendations for pwMS.
ABSTRACT
Introduciton: Multiple Sclerosis (MS) is an autoimmune disease with B-cell dysregulation playing an essential role in pathogenesis. As B-cells are also responsible for antibody production, their disfunction could also affect the humoral immune response against SARS-CoV-2 vaccines. Aim(s): To compare the immune response after messenger RNA (mRNA) BNT162b2 (Pfizer/BioNTech) and inactivated Coronavac vaccines in newly diagnosed treatment-naive MS (tnMS) patients and healthy controls (HC). Method(s): A single-center cross-sectional study evaluating antibody response against SARS-CoV-2 vaccines (inactivated vs mRNA) in HC and newly diagnosed and treatment-naive MS patients. Serum samples were collected at least two weeks after the second dose of the vaccine. The cutoff level of seropositivity is >= 50 antibody unit (AU)/ml. Result(s): 46 participants had two doses of inactivated Coronavac (35 HC and 11 tnMS), and 103 (57 HC and 46 tnMS) had two doses of mRNA. There was no significant difference in antibody response between HC and tnMS in the inactivated vaccine group. In the mRNA group, the antibody titers were significantly higher in HC (p=0.009), though no difference in the seropositivity rates was observed. Conclusion(s): Although MS is an autoimmune inflammatory disease, it does not affect immunity against the SARS-CoV-2 vaccine in treatment-naive patients.
ABSTRACT
Introduction: Patients with multiple sclerosis (MS) are commonly treated with B-cell depletion therapies (BCDTs). Reduced seroconversion following COVID-19 vaccination in patients receiving certain BCDTs has been reported, however the immune response following natural infection is poorly understood. Objective(s): This study aimed to evaluate COVID-19 antibody responses after vaccination and natural infection in BCDT-treated patients. This single-centre study evaluated COVID-19 seroconversion and spike protein antibody titres for double-vaccinated MS or neuroinflammatory disease patients treated with BCDT (n=33) with confirmed COVID-19 infection (n=16) or uninfected by COVID-19 (control;n=17). Method(s): We performed a retrospective review of patients at the Yale MS Center who had systematically checked COVID-19 spike antibody levels among patients treated with BCDTs (ocrelizumab [OCR], n=24;rituximab [RTX], n=5;ofatumumab [OFT], n=4). Data were collected from Mar 2020 to Feb 2022. All patients had received >=2 doses of FDA-approved COVID-19 vaccine. Qualitative spike antibody seropositivity was determined based on test-specific lab reference ranges. For a subset of patients (n=18), quantitative spike antibody levels were assessed via DiaSorin Liaison chemiluminescence assay (positive titre of >=13;OCR, n=13;RTX, n=3;OFT, n=2). Vaccination and COVID-19 infection dates were also recorded. Patients were monitored for health effects following COVID-19. Result(s): Overall,16/33 (48%) patients seroconverted post full vaccination. After COVID-19 infection, 15/16 (94%) seroconverted, while 7/17 (41%) of uninfected patients seroconverted after vaccination. For the 18 patients with quantitative COVID-19 spike antibody titres, mean titres post-vaccination were 37.38. Mean antibody titres were significantly higher after COVID-19 infection;540.32 vs 20.1 in the control group (p<0.05). Of the 16 infected patients, 15 had mild COVID-19 symptoms and 1 was asymptomatic. No hospitalizations or deaths were reported. Conclusion(s): This study reports that COVID-19 spike antibody titres in fully vaccinated, BCDT-treated patients were significantly increased post-infection compared to the control group. BCDT-treated patients infected with COVID-19 displayed mild infection or were asymptomatic, with no hospitalizations or deaths. These results provide reassurance that BCDTs in doublevaccinated MS patients do not preclude an appropriate COVID-19 antibody response post infection.
ABSTRACT
Introduction: The experience of suffering multiple sclerosis (MS) can generate patient personal benefit gain and self-improvement. The global pandemic might play a role in the development of post-trauma growth, as patients can perceive the 2019 coronavirus (Covid-19) as a higher threat than the average due to MS condition. Objectives/Aims: To study possible changes in post-traumatic growth in people with MS and Covid-19 influence. Method(s): The sample comprised 260 participants (179 women and 81 men), receiving health care at Virgen Macarena University Hospital. Mean age was 45.05 years (SD= 10.61), from 19 to 78 years old. The MS type were Relapsing-Remitting (n=228) and Progressive (n=32), the Expanded Disability Status Scale (EDSS) mean score was 3.21 (SD=1.93), and mean MS duration was 144.77 months since diagnosis (SD=89.33). Post-traumatic growth inventory (PGI-21) was applied to evaluate patient perception of personal benefit on two different occasions: (T1) 2018- 2019 and, 18 months later, (T2) 2020-2021. At T2, Covid-19 influence was appraised asking patients if they felt affected or not about the Covid situation. Paired t-test examine changes in Post- Traumatic Growth between T1 and T2. Unpaired t-test tested differences in patients affected (n=123) and not affected (n=137) by Covid-19 at T2. Result(s): From T1 to T2 every subscale: relating to others, new possibilities, personal strength, spiritual change, appreciation of life, and PGI-21 total score significantly increased (p<0.0001 for all). Patients affected by Covid-19 reported significant higher scores of PGI-21 subscales and total scores than patients stated not to be affected by Covid-19. Conclusion(s): Patients showed an increase in post-traumatic growth over an 18 months follow-up period, this suggest that elaborating a post-trauma growth is a process that might require time. Additionally, patients who felt affected by Covid-19 presented higher scores in post-traumatic growth. Feeling in an adverse situation, as a global pandemic, might promote the personal benefit gain process in MS.