SARS-CoV-2 omicron breakthrough infections in patients with multiple sclerosis

Kempen, Zoé L E van; Stalman, Eileen W; Steenhuis, Maurice; Kummer, Laura; Dam, Koos P J van; Brinke, Anja ten; Ham, S. Marieke van; Kuijpers, Taco W.; Rispens, Theo; Eftimov, Filip; Killestein, Joep

doi:10.1136/jnnp-2022-330100

Cited by 12 publications

(8 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study by Novak et al [27] found that 59% of patients on anti‐CD20 developed breakthrough non‐severe COVID‐19 after three injections of SARS‐CoV‐2 mRNA vaccine. Another study by van Kempen et al [28] found that patients on anti‐CD20 and S1PRM had a higher breakthrough COVID‐19 rate compared to patients on other treatments, but most infections were mild.…”

Section: Discussionmentioning

confidence: 99%

Three to four mRNA COVID‐19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization

Louapre¹,

Belin

Marot

et al. 2023

Euro J of Neurology

View full text Add to dashboard Cite

Background and purpose An enhanced severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine regimen could improve humoral vaccine response in patients with multiple sclerosis (MS) treated by anti‐CD20. The aim was to evaluate the serological response and the neutralizing activity after BNT162b2 primary and booster vaccination in MS patients, including patients on anti‐CD20 receiving a primary vaccine regimen enhanced with three injections. Methods In this prospective longitudinal cohort study of 90 patients (47 on anti‐CD20, 10 on fingolimod, 33 on natalizumab, dimethylfumarate or teriflunomide), anti‐SARS‐CoV‐2 receptor binding domain (RBD) immunoglobulin G antibodies were quantified and their neutralization capacity was evaluated by enzyme‐linked immunosorbent assay (GenScript) and a virus neutralization test against B.1 historical strain, Delta and Omicron variants, before and after three to four BNT162b2 injections. Results After the primary vaccination scheme, the anti‐RBD positivity rate was strongly decreased in patients on anti‐CD20 (28% [15%; 44%] after two shots, 45% [29%; 62%] after three shots) and fingolimod (50% [16%; 84%]) compared to other treatments (100% [90%; 100%]). Neutralization activity was also decreased in patients on anti‐CD20 and fingolimod, and notably low for the Omicron variant in all patients (0%–22%). Delayed booster vaccination was performed in 54 patients, leading to a mild increase of anti‐RBD seropositivity in patients on anti‐CD20 although it was still lower compared to other treatments (65% [43%; 84%] vs. 100% [87%; 100%] respectively). After a booster, Omicron neutralization activity remained low on anti‐CD20 and fingolimod treated patients but was strongly increased in patients on other treatments (91% [72%; 99%]). Discussion In MS patients on anti‐CD20, an enhanced primary vaccination scheme moderately increased anti‐RBD seropositivity and anti‐RBD antibody titre, but neutralization activity remained modest even after a fourth booster injection. Trial registration information COVIVAC‐ID, NCT04844489, first patient included on 20 April 2021.

show abstract

Section: Discussionmentioning

confidence: 99%

Three to four mRNA COVID‐19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization

Louapre¹,

Belin

Marot

et al. 2023

Euro J of Neurology

View full text Add to dashboard Cite

show abstract

“…Both responses were generally higher in patients who had a COVID-19 infection in addition to their vaccinations, which is in line with other published data in anti-CD20-treated patients as well as in the general population [ 11 , 25 , 33 , 34 , 35 ]. However, a few studies did not report a difference in antibody levels upon combined infection and vaccination [ 36 , 37 ]. In particular, hybrid immunity has been noted for its prominent effect on neutralizing SARS-CoV-2-specific antibodies, both in terms of their quantity and their neutralizing capacity with regard to a broad spectrum of variants [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Immune Response Profiles to SARS-CoV-2 Vaccination and Infection in People with Multiple Sclerosis on Anti-CD20 Therapy

Woopen,

Dunsche,

Al Rahbani

et al. 2023

Vaccines

View full text Add to dashboard Cite

Our objective was to analyze longitudinal cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in people with multiple sclerosis (pwMS) on B-cell depleting treatment (BCDT) compared to pwMS without immunotherapy. We further evaluated the impact of COVID-19 infection and vaccination timing. PwMS (n = 439) on BCDT (ocrelizumab, rituximab, ofatumumab) or without immunotherapy were recruited for this prospective cohort study between June 2021 and June 2022. SARS-CoV-2 spike-specific antibodies and interferon-γ release of CD4 and CD8 T-cells upon stimulation with spike protein peptide pools were analyzed at different timepoints (after primary vaccination, 3 and 6 months after primary vaccination, after booster vaccination, 3 months after booster). Humoral response to SARS-CoV-2 was consistently lower whereas T-cell response was higher in patients with BCDT compared to controls. Cellular and humoral responses decreased over time after primary vaccination and increased again upon booster vaccination, with significantly higher antibody titers after booster than after primary vaccination in both untreated and B-cell-depleted pwMS. COVID-19 infection further led to a significant increase in SARS-CoV-2-specific responses. Despite attenuated B-cell responses, a third vaccination for patients with BCDT seems recommendable, since at least partial protection can be expected from the strong T-cell response. Moreover, our data show that an assessment of T-cell responses may be helpful in B-cell-depleted patients to evaluate the efficacy of SARS-CoV-2 vaccination.

show abstract

“…10 However, these studies did not measure serology in all participants, instead focussing on clinical infection. Lack of seroconversion after initial vaccination, especially in the context of anti-CD20 and S1P treatments, has been reported to be associated with increased rates of COVID-19 by some, [11][12][13][14] but not all, 15 groups. The differential protective effect of vaccination against severe infections in those exposed to DMT associated with lower seroconversion is less clear, given the relative rarity of severe infection in the post-vaccination era.…”

Section: Risk Of Covid-19 In People With Multiple Sclerosis Who Are S...mentioning

confidence: 99%

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination

Zaloum,

Wood,

Tank

et al. 2023

Mult Scler

View full text Add to dashboard Cite

Background: People with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs) have attenuated IgG response following COVID-19 vaccination; however, the clinical consequences remain unclear. Objective: To report COVID-19 rates in pwMS according to vaccine serology. Methods: PwMS with available (1) serology 2–12 weeks following COVID-19 vaccine 2 and/or vaccine 3 and (2) clinical data on COVID-19 infection/hospitalisation were included. Logistic regression was performed to examine whether seroconversion following vaccination predicted risk of subsequent COVID-19 infection after adjusting for potential confounders. Rates of severe COVID-19 (requiring hospitalisation) were also calculated. Results: A total of 647 pwMS were included (mean age 48 years, 500 (77%) female, median Expanded Disability Status Scale (EDSS) 3.5% and 524 (81%) exposed to DMT at the time of vaccine 1). Overall, 472 out of 588 (73%) were seropositive after vaccines 1 and 2 and 222 out of 305 (73%) after vaccine 3. Seronegative status after vaccine 2 was associated with significantly higher odds of subsequent COVID-19 infection (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.34–4.12, p = 0.0029), whereas seronegative status after vaccine 3 was not (OR: 1.05, 95% CI: 0.57–1.91). Five people (0.8%) experienced severe COVID-19, all of whom were seronegative after most recent vaccination. Conclusion: Attenuated humoral response to initial COVID-19 vaccination predicts increased risk of COVID-19 in pwMS, but overall low rates of severe COVID-19 were seen.

show abstract

SARS-CoV-2 omicron breakthrough infections in patients with multiple sclerosis

Cited by 12 publications

References 12 publications

Three to four mRNA COVID‐19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization

Three to four mRNA COVID‐19 vaccines in multiple sclerosis patients on immunosuppressive drugs: Seroconversion and variant neutralization

Long-Term Immune Response Profiles to SARS-CoV-2 Vaccination and Infection in People with Multiple Sclerosis on Anti-CD20 Therapy

Risk of COVID-19 in people with multiple sclerosis who are seronegative following vaccination

Contact Info

Product

Resources

About