COVID-19 vaccine response in people with multiple sclerosis

Tallantyre, Emma; Vickaryous, Nicola; Anderson, Valerie; Asardag, Aliye Nazli; Baker, David; Bestwick, Jonathan P.; Bramhall, Kathryn; Chance, Randy; Evangelou, Nikos; George, Katila; Giovannoni, Gavin; Grant, Leanne; Harding, Katharine; Hibbert, Aimee; Ingram, Gillian; Jones, Meleri; Kang, Angray S.; Loveless, Samantha; Moat, Stuart; Robertson, Neil; Schmierer, Klaus; Shah, Sitash Navin; Simmons, Jessica; Upcott, Matthew; Willis, Mark; Jolles, Stephen; Dobson, Ruth

doi:10.1101/2021.07.31.21261326

Cited by 32 publications

(64 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, patients on S1P receptor modulators and anti-CD20 mAb had significantly reduced levels of total spike and spike RBD IgG, consistent with recent reports [8][9][10][11] . We did not observe a clear relationship between spike antibody seropositivity and anti-CD20 mAb infusion interval and SARS-CoV-2 vaccination, in contrast to several other studies 7,18,19,21 . It is possible this disparity could be due to differences in patient populations or methodology.…”

Section: Discussioncontrasting

confidence: 99%

“…Only RTX patients had a significant decrease in total spike IgG seropositivity (23.1% ± 12.2% SEM, p < 0.0001), whereas S1P, RTX, and OCR patients had significant reductions in spike RBD IgG seropositivity (42.9 ± 20.2% SEM, p = 0.02; 7.7 ± 7.7% SEM, p < 0.0001; 36.4 ± 10.5% SEM, p = 0.0001, respectively) ( Figure 1C ). These findings are consistent with recent reports indicating reductions in SARS-CoV-2 spike-specific antibodies in SARS-CoV-2 vaccinated MS patients on S1P receptor modulators and anti-CD20 mAb 7,18,19 .…”

Section: Resultssupporting

confidence: 93%

“…The copyright holder for this this version posted September 20, 2021. ; https://doi.org/10.1101/2021.09.10.21262933 doi: medRxiv preprint Given variability in timing of anti-CD20 mAb infusions caused by the ongoing SARS-CoV-2 pandemic, we also assessed whether differences in the interval between the last prior anti-CD20 mAb infusion and first SARS-CoV-2 vaccination could be related to vaccine-induced IgG responses, which has been reported previously 18,19 . In the combined anti-CD20 mAb cohorts, we did not observe any significant correlation between infusion to vaccination interval and total spike and spike RBD IgG levels (Supplemental Figure 2M-N).…”

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 99%

“…MS DMTs differ considerably in their mechanisms of action with variable impacts on humoral and cellular immune functions leading to associated risks of certain infections 2 . Coronavirus 19 (COVID- 19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has resulted in a pandemic since early 2020. Control of SARS-Cov-2 infection involves mobilization of antibody and T cell-mediated immunity [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, most MS DMTs have been previously reported to at least partially impact vaccine-elicited antibody and/or T cell immunity 16,17 . To date, the majority of studies evaluating SARS-CoV-2 vaccine responses in MS patients have been limited to measuring antibody titers, demonstrating reduced spike antigen-specific antibody responses in MS patients treated with anti-CD20 mAb and S1P receptor modulators 7,[18][19][20] . Several reports have also indicated largely intact spike antigenspecific T cell responses in vaccinated MS patients on anti-CD20 mAb 18,21 .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Sabatino

Mittl

Rowles

et al. 2021

Preprint

View full text Add to dashboard Cite

Vaccine-elicited adaptive immunity is an essential prerequisite for effective prevention and control of coronavirus 19 (COVID-19). Treatment of multiple sclerosis (MS) involves a diverse array of disease-modifying therapies (DMTs) that target antibody and cell-mediated immunity, yet a comprehensive understanding of how MS DMTs impact SARS-CoV-2 vaccine responses is lacking. We completed a detailed analysis of SARS-CoV-2 vaccine-elicited spike antigen-specific IgG and T cell responses in a cohort of healthy controls and MS participants in six different treatment categories. Two specific DMT types, sphingosine-1-phosphate (S1P) receptor modulators and anti-CD20 monoclonal antibodies (mAb), resulted in significantly reduced spike-specific IgG responses. Longer duration of anti-CD20 mAb treatment prior to SARS-CoV-2 vaccination were associated with absent antibody responses. Except for reduced CD4+ T cell responses in S1P-treated patients, spike-specific CD4+ and CD8+ T cell reactivity remained robust across all MS treatment types. These findings have important implications for clinical practice guidelines and vaccination recommendations in MS patients and other immunosuppressed populations.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Resultssupporting

confidence: 93%

Section: (Which Was Not Certified By Peer Review) Preprintmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Sabatino

Mittl

Rowles

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

Autoimmune Encephalitis Misdiagnosis in Adults

et al. 2023

View full text Add to dashboard Cite

ImportanceAutoimmune encephalitis misdiagnosis can lead to harm.ObjectiveTo determine the diseases misdiagnosed as autoimmune encephalitis and potential reasons for misdiagnosis.Design, Setting, and ParticipantsThis retrospective multicenter study took place from January 1, 2014, to December 31, 2020, at autoimmune encephalitis subspecialty outpatient clinics including Mayo Clinic (n = 44), University of Oxford (n = 18), University of Texas Southwestern (n = 18), University of California, San Francisco (n = 17), University of Washington in St Louis (n = 6), and University of Utah (n = 4). Inclusion criteria were adults (age ≥18 years) with a prior autoimmune encephalitis diagnosis at a participating center or other medical facility and a subsequent alternative diagnosis at a participating center. A total of 393 patients were referred with an autoimmune encephalitis diagnosis, and of those, 286 patients with true autoimmune encephalitis were excluded.Main Outcomes and MeasuresData were collected on clinical features, investigations, fulfillment of autoimmune encephalitis criteria, alternative diagnoses, potential contributors to misdiagnosis, and immunotherapy adverse reactions.ResultsA total of 107 patients were misdiagnosed with autoimmune encephalitis, and 77 (72%) did not fulfill diagnostic criteria for autoimmune encephalitis. The median (IQR) age was 48 (35.5-60.5) years and 65 (61%) were female. Correct diagnoses included functional neurologic disorder (27 [25%]), neurodegenerative disease (22 [20.5%]), primary psychiatric disease (19 [18%]), cognitive deficits from comorbidities (11 [10%]), cerebral neoplasm (10 [9.5%]), and other (18 [17%]). Onset was acute/subacute in 56 (52%) or insidious (&gt;3 months) in 51 (48%). Magnetic resonance imaging of the brain was suggestive of encephalitis in 19 of 104 patients (18%) and cerebrospinal fluid (CSF) pleocytosis occurred in 16 of 84 patients (19%). Thyroid peroxidase antibodies were elevated in 24 of 62 patients (39%). Positive neural autoantibodies were more frequent in serum than CSF (48 of 105 [46%] vs 7 of 91 [8%]) and included 1 or more of GAD65 (n = 14), voltage-gated potassium channel complex (LGI1 and CASPR2 negative) (n = 10), N-methyl-d-aspartate receptor by cell-based assay only (n = 10; 6 negative in CSF), and other (n = 18). Adverse reactions from immunotherapies occurred in 17 of 84 patients (20%). Potential contributors to misdiagnosis included overinterpretation of positive serum antibodies (53 [50%]), misinterpretation of functional/psychiatric, or nonspecific cognitive dysfunction as encephalopathy (41 [38%]).Conclusions and RelevanceWhen evaluating for autoimmune encephalitis, a broad differential diagnosis should be considered and misdiagnosis occurs in many settings including at specialized centers. In this study, red flags suggesting alternative diagnoses included an insidious onset, positive nonspecific serum antibody, and failure to fulfill autoimmune encephalitis diagnostic criteria. Autoimmune encephalitis misdiagnosis leads to morbidity from unnecessary immunotherapies and delayed treatment of the correct diagnosis.

show abstract

Hybrid and vaccine‐induced immunity against SAR‐CoV‐2 in MS patients on different disease‐modifying therapies

Kister

Curtin

Pei³

et al. 2022

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective: To compare "hybrid immunity" (prior COVID-19 infection plus vaccination) and post-vaccination immunity to SARS CoV-2 in MS patients on different disease-modifying therapies (DMTs) and to assess the impact of vaccine product and race/ethnicity on post-vaccination immune responses. Methods: Consecutive MS patients from NYU MS Care Center (New York, NY), aged 18-60, who completed primary COVID-19 vaccination series ≥6 weeks previously were evaluated for SARS CoV-2-specific antibody responses with electro-chemiluminescence and multiepitope bead-based immunoassays and, in a subset, live virus immunofluorescence-based microneutralization assay. SARS CoV-2-specific cellular responses were assessed with cellular stimulation TruCulture IFNc and IL-2 assay and, in a subset, with IFNc and IL-2 ELISpot assays. Multivariate analyses examined associations between immunologic responses and prior COVID-19 infection while controlling for age, sex, DMT at vaccination, time-to-vaccine, and vaccine product. Results: Between 6/01/2021 and 11/11/2021, 370 MS patients were recruited (mean age 40.6 years; 76% female; 53% non-White; 22% with prior infection; common DMT classes: ocrelizumab 40%; natalizumab 15%, sphingosine-1-phosphate receptor modulators 13%; and no DMT 8%). Vaccine-to-collection time was 18.7 (AE7.7) weeks and 95% of patients received mRNA vaccines. In multivariate analyses, patients with laboratory-confirmed prior COVID-19 infection had significantly increased antibody and cellular post-vaccination responses compared to those without prior infection. Vaccine product and DMT class were independent predictors of antibody and cellular responses, while race/ethnicity was not. Interpretation: Prior COVID-19 infection is associated with enhanced antibody and cellular postvaccine responses independent of DMT class and vaccine type. There were no differences in immune responses across race/ethnic groups.

show abstract

COVID-19 vaccine response in people with multiple sclerosis

Cited by 32 publications

References 36 publications

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Impact of multiple sclerosis disease-modifying therapies on SARS-CoV-2 vaccine-induced antibody and T cell immunity

Autoimmune Encephalitis Misdiagnosis in Adults

Hybrid and vaccine‐induced immunity against SAR‐CoV‐2 in MS patients on different disease‐modifying therapies

Contact Info

Product

Resources

About