Breakthrough SARS-CoV-2 infections in MS patients on disease modifying therapies

Schiavetti, Irene; Cordioli, Cinzia; Stromillo, Maria Laura; Ferrò, Maria Teresa; Laroni, Alice; Cocco, Eleonora; Cola, Gaia; Pasquali, Livia; Rilla, Maria Teresa; Signoriello, Elisabetta; Iodice, Rosa; Sapio, Alessia Di; Lanzillo, Roberta; Caleri, Francesca; Annovazzi, Pietro; Conte, Antonella; Liberatore, Giuseppe; Ruscica, Francesca; Docimo, Renato; Bonavita, Simona; Ulivelli, Monica; Cavalla, Paola; Patti, Francesco; Ferraro, Diana; Clerico, Marinella; Immovilli, Paolo; Salvetti, Marco; Sormani, Maria Pia

doi:10.1101/2022.01.22.22269630

Cited by 9 publications

(18 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

“…The less-extensive humoral blunts in pwMS on TERI – and possibly ALEM – do not seem to have had any significant effect on vaccine effectiveness. Regarding the protective effect of T-cell responses, currently, the only clue lies within the Etemadifar et al 72 study – although not confirmed by a larger study 73 ; it showed that among the vaccinated pwMS, the ones on aCD20 experienced lower incidence and severity of COVID-19 in comparison with those on fingolimod. The former are known to be prone to worse COVID-19 outcomes 64 but show robust post-vaccination T-cell responses, while the latter do not develop proper T-cell immunization following vaccination.…”

Section: Resultsmentioning

confidence: 94%

“…The less-extensive humoral blunts in pwMS on TERI -and possibly ALEM -do not seem to have had any significant effect on vaccine effectiveness. Regarding the protective effect of T-cell responses, currently, the only clue lies within the Etemadifar et al 72 study -although not confirmed by a larger study 73 ; it showed that among the vaccinated pwMS, the ones on aCD20 experienced lower incidence and severity All rights reserved. No reuse allowed without permission.…”

Section: Moving Into the Clinicmentioning

confidence: 94%

See 2 more Smart Citations

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

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 94%

Section: Moving Into the Clinicmentioning

confidence: 94%

See 1 more Smart Citation

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

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Overall, CMI in anti-CD20-treated patients may be diminished or at least very heterogeneous after 2 or 3 SARS-CoV-2 vaccinations, depending on patient population or comedication 4. Together with the ubiquitously reported impaired humoral responses to SARS-CoV-2 vaccines in anti-CD20-treated patients, the consequence is undoubtedly an increased risk of severe breakthrough infections in this population, as reported from two potentially overlapping study populations 28 29…”

Section: Discussionmentioning

confidence: 95%

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy

et al. 2022

View full text Add to dashboard Cite

BackgroundThe majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients.MethodsWe investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6–4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression.Results5.6 months (IQR: 5.1–6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0–7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants.ConclusionThis study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.

show abstract

“…In this case, the hospitalization rate was higher in ocrelizumab patients compared with fingolimod or the rest of pwMS (16.7%, 3.6% and 3.9% respectively). 21 SARS-CoV-2 vaccines have demonstrated to be safe in pwMS and other demyelinating diseases. However, some rare cases of neurological adverse events, including new diagnoses of MS, transverse myelitis, acute disseminated encephalomyelitis (ADEM) or MS relapses, are being described after all types of SARS-CoV-2 vaccines.…”

Section: Two Years Of Covid-19 In the Ms Communitymentioning

confidence: 99%

Two years of COVID-19 in the MS community: What have we learnt so far?

2022

View full text Add to dashboard Cite

Breakthrough SARS-CoV-2 infections in MS patients on disease modifying therapies

Cited by 9 publications

References 13 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

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy

Two years of COVID-19 in the MS community: What have we learnt so far?

Contact Info

Product

Resources

About