Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy

Gadani, Sachin P.; Reyes‐Mantilla, Maria; Jank, Larissa; Harris, S.D.; Douglas, Morgan; Smith, Matthew D.; Calabresi, Peter A.; Mowry, Ellen M.; Fitzgerald, Kathryn C.; Bhargava, Pavan

doi:10.1016/j.ebiom.2021.103636

Cited by 90 publications

(101 citation statements)

References 24 publications

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“…A small number of vaccinated patients in the ALITHIOS study and post-marketing setting reported breakthrough infections of which most cases were of mild-to-moderate severity and had a non-serious nature; all recovered. The immunization response to COVID-19 vaccinations is complex involving an interplay of both cellular and humoral immunity [ 42 ], both of which could be impaired because of B-cell depletion [ 19 – 21 ] Studies that further evaluate immunization responses to COVID-19 vaccination in patients on ofatumumab therapy are in progress. A COVID-19 vaccination sub-study embedded in the ALITHIOS open-label extension is underway to investigate the effect of ofatumumab on humoral and T-cell responses following selected COVID-19 vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Opinions were published during the COVID-19 pandemic recommending delayed dosing for B-cell–depleting therapies based on a perception of increased risk of COVID-19 [ 14 , 17 , 18 ]. In addition, some studies have observed that B-cell therapies impact humoral responses to COVID-19 vaccination [ 19 – 21 ]. Although much was learned since the start of the pandemic, healthcare professionals (HCPs) continue to face uncertainties in the management of patients with MS in routine clinical practice and are concerned with potential reinfections, waning effect of vaccination, and vaccine breakthrough infections.…”

Section: Introductionmentioning

confidence: 99%

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COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

et al. 2022

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Introduction The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results As of 25 September 2021, 245 of 1703 patients (14.3%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients were hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious ( n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon. Supplementary Information The online version contains supplementary material available at 10.1007/s40120-022-00341-z.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

et al. 2022

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“…( Apostolidis et al, 2021 Sep 14 ) Moreover, several subsequent studies confirmed that pwMS who were treated with ocrelizumab generated comparable SARS-CoV-2-specific T-cell responses with healthy controls and/or pwMS on other MS therapies. ( Brill et al, 2021 Sep 23 , Sabatino et al, 2022 Jan 14 , Gadani et al, 2021 Oct 16 , Madelon et al, 2021 )…”

Section: Discussionmentioning

confidence: 99%

Humoral and cellular immunity in convalescent and vaccinated COVID-19 people with multiple sclerosis: Effects of disease modifying therapies

Habek

Cvetić

Mlakar

et al. 2022

Multiple Sclerosis and Related Disorders

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Objectives : To determine anti-SARS-Cov2 antibodies and T-cell immunity in convalescent people with multiple sclerosis (pwMS) and/or pwMS vaccinated against Covid-19, depending on the disease modifying therapy, and in comparison to healthy controls (HC). Methods : 75 participants were enrolled: Group 1—29 (38.7%) COVID-19 convalescent participants; Group 2—34 (45.3%) COVID-19 vaccinated; Group 3—12 (16.0%) COVID-19 convalescent participants who were later vaccinated against COVID-19. Cellular immunity was evaluated by determination of number of CD4+ and CD8+ cells secreting TNFα, IFNγ, and IL2 after stimulation with SARS-CoV-2 peptides. Results : pwMS treated with ocrelizumab were less likely to develop humoral immunity after COVID-19 recovery or vaccination. No difference was observed in the cellular immunity in all studied parameters between pwMS treated with ocrelizumab compared to HC or pwMS who were treatment naïve or on first line therapies. These findings were consistent in convalescent, vaccinated, and convalescent+vaccinated participants. COVID-19 vaccinated convalescent pwMS on ocrelizumab compared to COVID-19 convalescent HC who were vaccinated did not show statistically difference in the rate of seroconversion nor titers of SARS-CoV-2 antibodies. Conclusion : Presence of cellular immunity in pwMS on B-cell depleting therapies is reassuring, as at least partial protection from more severe COVID-19 outcomes can be expected.

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“…In this study all pwMS treated with aCD20 therapy generated antigen-specific CD4 and CD8 T cell responses after vaccination ( Apostolidis et al, 2021 ). Moreover, several subsequent studies, some of which have still not been peer-reviewed, confirmed that pwMS who were treated with ocrelizumab generated comparable SARS-CoV-2-specific T-cell responses with healthy controls and/or pwMS on other MS therapies ( Brill et al, 2021 ; Sabatino et al, 2021 ; Gadani et al, 2021 ). However, it is not yet clear to which extent of T cell response and for how long it is adequate to protect patients against virus infection after recovery from COVID-19 or vaccination.…”

Section: Discussionmentioning

confidence: 95%

Humoral and cellular immunity in convalescent COVID-19 people with multiple sclerosis treated with ofatumumab

Adamec

Rogić

Penz

et al. 2022

Journal of Neuroimmunology

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Objectives To report clinical outcome, development of humoral and T-cell mediated immunity in convalescent COVID-19 people with multiple sclerosis (pwMS) treated with ofatumumab in the ALITHIOS study from a single center. Methods Testing for SARS-Cov2 IgG antibodies was performed on two occasions with at least three months apart between the two testing. During the second antibody testing, interferon-γ ELISpot was used to assess cellular immunity. Results All four subjects had mild COVID-19 infection without any sequelae. In all subjects except subject 2, COVID-19 was confirmed with PCR. Subjects 1, 2 and 4 had normal levels of IgM and IgG without measurable counts of CD19 cells prior to COVID-19. Subject 3 administered the last dose of ofatumumab 24 days prior to COVID-19 symptoms, but had a gap of 28 weeks of ofatumumab application beforehand due to low IgM levels. Subject 4 received COVID-19 vaccinations before second testing, so second testing and T-cell immunity testing were not performed. Subjects who were CD19 depleted did not had measurable levels of SARS-Cov2 IgG antibodies. Subject 3 had first and second SARS-COV2 titer of 118 U/ml and > 250 U/ml, respectively. All three pwMS showed T cell immunity against SARS-CoV-2. Quotient of basal spots divided by interferon-γ secreting spot forming units were 4, 8 and 14.7 SI in subjects 1, 2 and 3, respectively (>3 considered reactive). Conclusion While no antibody response was observed in pwMS who were CD19+ lymphocyte depleted, T cell immunity against SARS-CoV-2 was observed in all three pwMS treated with ofatumumab.

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Discordant humoral and T cell immune responses to SARS-CoV-2 vaccination in people with multiple sclerosis on anti-CD20 therapy

Cited by 90 publications

References 24 publications

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

Humoral and cellular immunity in convalescent and vaccinated COVID-19 people with multiple sclerosis: Effects of disease modifying therapies

Humoral and cellular immunity in convalescent COVID-19 people with multiple sclerosis treated with ofatumumab

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