T-cell responses to SARS-CoV-2 in multiple sclerosis patients treated with ocrelizumab healed from COVID-19 with absent or low anti-spike antibody titers

Iannetta, Marco; Landi, Doriana; Cola, Gaia; Malagnino, Vincenzo; Teti, Elisabetta; Fraboni, Daniela; Buccisano, Francesco; Grelli, Sandro; Coppola, Luigi; Campogiani, Laura; Andreoni, Massimo; Marfia, Girolama Alessandra; Sarmati, Loredana

doi:10.1016/j.msard.2021.103157

Cited by 34 publications

(40 citation statements)

References 11 publications

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“…( Bar-Or et al, 2020 ) In OCR-treated patients, several studies have shown an impaired humoral response yet preserved T-cell response following SARS-CoV-2 infection or vaccination with Pfizer-BioNTech COVID-19 (BNT162b2) or Moderna Tx, Inc (mRNA-1273). ( Kister et al, 2021 , Achiron et al, 2021 , Sormani et al, 2021 , Apostolidis et al, 2021 , Iannetta et al, 2021 ) In contrast, natalizumab (NTZ), an α4-integrin monoclonal antibody, is unlikely to impact vaccine efficacy. ( Kaufman et al, 2014 )…”

Section: Introductionmentioning

confidence: 99%

“…2 In OCR-treated patients, several studies have shown an impaired humoral response yet preserved T-cell response following SARS-CoV-2 infection or vaccination with Pfizer-BioNTech COVID- 19 (BNT162b2) or Moderna Tx, Inc (mRNA-1273). [7][8][9][10][11] In contrast, natalizumab (NTZ), an α4-integrin monoclonal antibody, is unlikely to impact vaccine efficacy. 12 In this study, we evaluated the humoral response to SARS-CoV-2 vaccines in adult MS patients treated with OCR, using NTZ as a real-world comparator.…”

Section: Introductionmentioning

confidence: 99%

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Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab

Katz¹,

Bouley²,

Jungquist³

et al. 2022

Multiple Sclerosis and Related Disorders

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab

Katz¹,

Bouley²,

Jungquist³

et al. 2022

Multiple Sclerosis and Related Disorders

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“…We have previously investigated SARS-CoV-2 specific T-cell responses in PwMS on ocrelizumab treatment, healed from COVID-19, using an interferon (IFN)-γ release assay (IGRA) after overnight stimulation of whole blood with SARS-CoV-2 specific peptide libraries. Despite the lack of an antibody response to the natural infection, we were able to identify a specific T-cell response in all the healed subjects included in the study ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

B- and T-Cell Responses After SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Receiving Disease Modifying Therapies: Immunological Patterns and Clinical Implications

Iannetta

Landi²,

Cola³

et al. 2022

Front. Immunol.

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BackgroundVaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19).MethodsPwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty®) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1.ResultsThirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD.ConclusionsThe evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.

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“…Some studies of SARS-CoV-2 infection and vaccination have already described specific cellular responses in the absence of humoral responses. 12 , 13 , 29 In fact, a study of COVID-19 patients with hematologic cancer treated with rituximab showed that those with a higher proportion of T cells had a better outcome. 30 Therefore, the cellular response might play an important role in COVID-19 recovery when humoral immunity is impaired.…”

Section: Discussionmentioning

confidence: 99%

Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis

Zabalza

Arrambide²,

Tagliani³

et al. 2022

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesInformation about humoral and cellular responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antibody persistence in convalescent (COVID-19) patients with multiple sclerosis (PwMS) is scarce. The objectives of this study were to investigate factors influencing humoral and cellular responses to SARS-CoV-2 and its persistence in convalescent COVID-19 PwMS.MethodsThis is a retrospective study of confirmed COVID-19 convalescent PwMS identified between February 2020 and May 2021 by SARS-CoV-2 antibody testing. We examined relationships between demographics, MS characteristics, disease-modifying therapy (DMT), and humoral (immunoglobulin G against spike and nucleocapsid proteins) and cellular (interferon-gamma [IFN-γ]) responses to SARS-CoV-2.ResultsA total of 121 (83.45%) of 145 PwMS were seropositive, and 25/42 (59.5%) presented a cellular response up to 13.1 months after COVID-19. Anti–CD20-treated patients had lower antibody titers than those under other DMTs (p < 0.001), but severe COVID-19 and a longer time from last infusion increased the likelihood of producing a humoral response. IFN-γ levels did not differ among DMT. Five of 7 (71.4%) anti-–CD20-treated seronegative patients had a cellular response. The humoral response persisted for more than 6 months in 41/56(81.13%) PwMS. In multivariate analysis, seropositivity decreased due to anti-CD20 therapy (OR 0.08 [95% CI 0.01–0.55]) and increased in males (OR 3.59 [1.02–12.68]), whereas the cellular response decreased in those with progressive disease (OR 0.04 [0.001–0.88]). No factors were associated with antibody persistence.DiscussionHumoral and cellular responses to SARS-CoV-2 are present in COVID-19 convalescent PwMS up to 13.10 months after COVID-19. The humoral response decreases under anti-CD20 treatment, although the cellular response can be detected in anti–CD20-treated patients, even in the absence of antibodies.

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T-cell responses to SARS-CoV-2 in multiple sclerosis patients treated with ocrelizumab healed from COVID-19 with absent or low anti-spike antibody titers

Cited by 34 publications

References 11 publications

Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab

Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab

B- and T-Cell Responses After SARS-CoV-2 Vaccination in Patients With Multiple Sclerosis Receiving Disease Modifying Therapies: Immunological Patterns and Clinical Implications

Humoral and Cellular Responses to SARS-CoV-2 in Convalescent COVID-19 Patients With Multiple Sclerosis

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