A retrospective evaluation of seroconversion after COVID-19 during the early Omicron wave in fully vaccinated multiple sclerosis patients receiving anti-CD20 therapies

Stoll, Sharon; Desai, Shree; Levit, Elle

doi:10.1016/j.msard.2023.104574

Cited by 4 publications

(4 citation statements)

References 23 publications

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“…Our study shows a pronounced impact of COVID-19 infection on antibody and T-cell responses. 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 ].…”

Section: Discussionsupporting

confidence: 90%

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

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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.

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Section: Discussionsupporting

confidence: 90%

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

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“…In line with these retrospective results, it has recently been shown in a prospective setting that ofatumumab-treated patients respond to initial vaccination against SARS-CoV-2 and while neutralizing antibody titers were reduced under ofatumumab, T-cell response was not affected [ 11 , 12 ]. SARS-CoV-2 infections after two doses of vaccine in patients receiving anti-CD20 antibodies were reported to be mild or asymptomatic and almost all patients seroconverted after infection [ 13 ]. Similarly, it has been suggested that booster vaccinations are of particular relevance for increasing antibody titers [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Results on SARS-CoV-2 mRNA Vaccine Booster from an Open-Label Multicenter Study in Ofatumumab-Treated Participants with Relapsing Multiple Sclerosis

et al. 2023

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Background: Few data exist on how ofatumumab treatment impacts SARS-CoV-2 booster vaccination response. Methods: KYRIOS is an ongoing prospective open-label multicenter study on the response to initial and booster SARS-CoV-2 mRNA vaccination before or during ofatumumab treatment in relapsing MS patients. The results on the initial vaccination cohort have been published previously. Here, we describe 23 patients who received their initial vaccination outside of the study but booster vaccination during the study. Additionally, we report the booster results of two patients in the initial vaccination cohort. The primary endpoint was SARS-CoV-2-specific T-cell response at month 1. Furthermore, serum total and neutralizing antibodies were measured. Results: The primary endpoint was reached by 87.5% of patients with booster before (booster cohort 1, N = 8) and 46.7% of patients with booster during ofatumumab treatment (booster cohort 2, N = 15). Seroconversion rates for neutralizing antibodies increased from 87.5% at baseline to 100.0% at month 1 in booster cohort 1 and from 71.4% to 93.3% in booster cohort 2. Of note, 3 of 4 initially seronegative patients in booster cohort 2 and one seronegative patient in the initial vaccination cohort seroconverted after the booster during ofatumumab treatment. Conclusions: Booster vaccinations increase neutralizing antibody titers in ofatumumab-treated patients. A booster is recommended in ofatumumab-treated patients.

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“…IL-1β is primarily a mediator of innate immune response, yet it serves as a key mediator of inflammatory response to mRNA immunization by stimulating the release of other proinflammatory cytokines. 33 The WHO ATC L category encompasses diverse immunosuppressive and immunomodulating agents, each potentially influencing IL-1β levels differently based on their mechanism of action. For instance, while aromatase inhibitors may not alter serum IL-1β levels, drugs like the IL-1 receptor antagonist anakinra can directly inhibit IL-1β activity.…”

Section: Discussionmentioning

confidence: 99%

Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile

New,

Cham,

Smith

et al. 2024

J Immunother Cancer

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BackgroundDespite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging.MethodsAn observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization.ResultsPrescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile.ConclusionsAntineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

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A retrospective evaluation of seroconversion after COVID-19 during the early Omicron wave in fully vaccinated multiple sclerosis patients receiving anti-CD20 therapies

Cited by 4 publications

References 23 publications

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

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

Results on SARS-CoV-2 mRNA Vaccine Booster from an Open-Label Multicenter Study in Ofatumumab-Treated Participants with Relapsing Multiple Sclerosis

Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile

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