Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England

Garjani, Alireza; Patel, Sameer; Bharkhada, Dhiren; Rashid, Waqar; Coles, Alasdair; Law, Graham; Evangelou, Nikos

doi:10.1016/j.msard.2021.103458

Cited by 45 publications

(44 citation statements)

References 9 publications

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“…However, in the absence of humoral immunization, it is doubted if the T-cells could provide adequate clinical protection among pwMS on aCD20 and S1PRM. The current real-world evidence confirms the predictive effect of seroconversion on post-vaccination COVID-19 incidence and severity 62 , and indicates rising comparative incidence and severity of COVID-19 among pwMS on S1PRM and aCD20 following vaccination of pwMS 62,71-73 . The less-extensive humoral blunts in pwMS on TERI – and possibly ALEM – do not seem to have had any significant effect on vaccine effectiveness.…”

Section: Resultssupporting

confidence: 69%

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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Importance: An evidence-based appraisal of the COVID-19 vaccination policies among people with multiple sclerosis (pwMS) with respect to disease-modifying therapies (DMT) is important for our understandings and their further management. Objective: To synthesize the available evidence concerning the effect of DMTs on COVID-19 vaccination immunogenicity and effectiveness. Data Sources: We searched MEDLINE, Scopus, Web of Science, MedRxiv, and Google Scholar from January 2021 until January 2022. Study Selection: The exclusion criteria included: not a primary investigation; retracted/withdrawn; no eligible participants - people with no history/evidence of previous COVID-19 and corticosteroid administration within two months of vaccination; no eligible exposures - all nine DMT classes; and no eligible comparators - DMT-unexposed at the time of vaccination. Data Extraction and Synthesis: Entries were assessed independently by two reviewers for eligibility and quality. Dichotomized data was extracted by two reviewers in accordance with Cochrane guidelines, and were pooled using either Peto fixed-effects or Inverse-variance random-effects methods. Main Outcomes and Measures: Main outcomes were i) B-cell response, measured by seroconversion odds ratio (OR); ii) T-cell response, measured by interferon-gamma release response OR, and CD4+/CD8+ activation-induced marker+ OR. Further outcomes including immunity waning speed and breakthrough COVID-19 incidence/severity were synthesized narratively. Results: Data from 28 studies (5,025 pwMS and 1,635 healthy participants) after COVID-19 vaccination suggests mildly-lower B-cell responses in teriflunomide- and alemtuzumab-treated, extensively-lower B-cell responses in sphingosine-1-phosphate receptor modulator (S1PRM)- and anti-CD20 (aCD20)-treated, and lower T-cell responses in interferon-, S1PRM-, alemtuzumab- and cladribine-treated pwMS. Every ten-week increase in aCD20-to-vaccine period is associated with a 1.94-time (95%CI: 1.57, 2.41, P<0.00001) increase in odds of seroconversion. B-cell-depleting therapies seem to accelerate post-vaccination humoral waning, and booster immunogenicity is predictable with the same factors affecting the priming vaccination. Furthermore, comparatively-increased breakthrough COVID-19 incidence and severity is being observed only among S1PRM- and anti-CD20-treated pwMS - i.e., among the pwMS with extensively-blunted B-cell response, despite adequate T-cell responses in the aCD20-treated. To date, pwMS on only-T-cell-blunting DMTs have not shown increased susceptibility to breakthrough COVID-19. Conclusion and Relevance: The implemented vaccination strategy to date has been effective for pwMS on all DMTs other than S1PRM and aCD20. As B-cell immunity seems to be a more important predictor of vaccine effectiveness than T-cell immunity, optimization of humoral immunogenicity and ensuring its durability among pwMS on DMTs are the necessities of an effective COVID-19 vaccination policy.

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Section: Resultssupporting

confidence: 69%

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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“…Many pwMS exposed to disease modifying therapies (DMTs) have an attenuated response to initial COVID-19 vaccination. This has been most profound when measuring humoral immunity in those exposed to anti-CD20s, and fits with data showing an increased vulnerability to COVID-19 amongst this group [6][7][8].…”

Section: Discussionsupporting

confidence: 83%

Response to COVID-19 booster vaccinations in seronegative people with MS

Tallantyre

Scurr

Vickaryous

et al. 2022

Preprint

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Importance: Uncertainties remain about the benefit of a 3rd COVID-19 vaccine for people with attenuated response to earlier vaccines. This is of particular relevance for people with multiple sclerosis (pwMS) treated with anti-CD20 therapies and fingolimod, who have substantially reduced antibody responses to initial vaccine course. Objective: To report humoral and T-cell responses following COVID-19 vaccine 3 in pwMS who were seronegative after COVID-19 vaccines 1&2. Design, setting and participants: PwMS taking part in a seroprevalence study without a detectable IgG response following COVID-19 vaccines 1&2 were invited to participate. Participants provided a dried blood spot +/- venous blood sample 2-12 weeks following COVID-19 vaccine 3. Data on demographics, MS treatment, and COVID-19 infection/vaccine dates were derived from the medical notes. Methods: Humoral and T cell responses to SARS-CoV-2 spike protein and nucleocapsid antigen were measured. The relationship between evidence of prior COVID-19 infection and immune response to COVID-19 vaccine 3 was evaluated using Fishers exact test. Results: Of 81 participants, 79 provided a dried blood spot sample, of whom 38 also provided a whole blood sample; 2 provided only whole blood. Anti-SARS-CoV-2-spike IgG seroconversion post-COVID-19 vaccine 3 occurred in 26/79 (33%) participants; 26/40 (65%) had positive T-cell responses. Overall, 31/40 (78%) demonstrated either humoral or cellular immune response post-COVID-19 vaccine 3. There no association between laboratory evidence of prior COVID-19 infection and anti-spike seroconversion following COVID-19 vaccine 3. Conclusions: Approximately one third of pwMS who were seronegative after initial COVID-19 vaccination seroconverted after booster (third) vaccination, supporting the use of boosters in this group. Almost 8 out of 10 had a measurable immune response following 3rd COVID-19 vaccine.

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“…Taken together, our data suggests that previously infected or vaccinated patients on aCD20 are less likely to be protected against “breakthrough” infection than others, a prediction borne out by a recent population‐based study from the United Kingdom, 43 but are probably still protected against COVID progression due to intact T‐cell immunity. 15 , 18 , 44 , 45 Memory T cells that contribute to protection against severe disease by eliminating infected cells and limiting viral replication may explain, at least in part, why vaccines prevent hospitalizations and deaths even against variants that exhibit limited neutralization by vaccine‐induced humoral immunity.…”

Section: Discussionmentioning

confidence: 63%

Cellular and Humoral Immunity to SARS‐CoV‐2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease‐Modifying Therapies: A Multi‐Ethnic Observational Study

Kister

Patskovsky

Curtin

et al. 2022

Annals of Neurology

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Objective The objective of this study was to determine the impact of multiple sclerosis (MS) disease‐modifying therapies (DMTs) on the development of cellular and humoral immunity to severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Methods Patients with MS aged 18 to 60 years were evaluated for anti‐nucleocapsid and anti‐Spike receptor‐binding domain (RBD) antibody with electro‐chemiluminescence immunoassay; antibody responses to Spike protein, RBD, N‐terminal domain with multiepitope bead‐based immunoassays (MBI); live virus immunofluorescence‐based microneutralization assay; T‐cell responses to SARS‐CoV‐2 Spike using TruCulture enzyme‐linked immunosorbent assay (ELISA); and IL‐2 and IFNγ ELISpot assays. Assay results were compared by DMT class. Spearman correlation and multivariate analyses were performed to examine associations between immunologic responses and infection severity. Results Between January 6, 2021, and July 21, 2021, 389 patients with MS were recruited (mean age 40.3 years; 74% women; 62% non‐White). Most common DMTs were ocrelizumab (OCR)—40%; natalizumab —17%, Sphingosine 1‐phosphate receptor (S1P) modulators −12%; and 15% untreated. One hundred seventy‐seven patients (46%) had laboratory evidence of SARS‐CoV‐2 infection; 130 had symptomatic infection, and 47 were asymptomatic. Antibody responses were markedly attenuated in OCR compared with other groups (p ≤0.0001). T‐cell responses (IFNγ) were decreased in S1P (p = 0.03), increased in natalizumab (p <0.001), and similar in other DMTs, including OCR. Cellular and humoral responses were moderately correlated in both OCR (r = 0.45, p = 0.0002) and non‐OCR (r = 0.64, p <0.0001). Immune responses did not differ by race/ethnicity. Coronavirus disease 2019 (COVID‐19) clinical course was mostly non‐severe and similar across DMTs; 7% (9/130) were hospitalized. Interpretation DMTs had differential effects on humoral and cellular immune responses to SARS‐CoV‐2 infection. Immune responses did not correlate with COVID‐19 clinical severity in this relatively young and nondisabled group of patients with MS. ANN NEUROL 2022;91:782–795

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Impact of mass vaccination on SARS-CoV-2 infections among multiple sclerosis patients taking immunomodulatory disease-modifying therapies in England

Cited by 45 publications

References 9 publications

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

Multiple sclerosis disease-modifying therapies and COVID-19 vaccines: A practical review and meta-analysis

Response to COVID-19 booster vaccinations in seronegative people with MS

Cellular and Humoral Immunity to SARS‐CoV‐2 Infection in Multiple Sclerosis Patients on Ocrelizumab and Other Disease‐Modifying Therapies: A Multi‐Ethnic Observational Study

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