Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies

Sormani, Maria Pia; Schiavetti, Irene; Inglese, Matilde; Carmisciano, Luca; Laroni, Alice; Lapucci, Caterina; Visconti, Valeria; Serrati, Carlo; Gandoglia, Ilaria; Tassinari, Tiziana; Perego, Germana; Brichetto, Giampaolo; Gazzola, Paola; Mannironi, Antonio; Stromillo, Maria Laura; Cordioli, Cinzia; Bovis, Francesca; Clerico, Marinella; Signoriello, Elisabetta; Frau, Jessica; Ferrò, Maria Teresa; Sapio, Alessia Di; Pasquali, Livia; Ulivelli, Monica; Marinelli, F.; Manzino, M; Callari, Graziella; Iodice, Rosa; Liberatore, Giuseppe; Caleri, Francesca; Repice, Anna Maria; Cordera, Susanna; Battaglia, Mario Alberto; Salvetti, Marco; Franciotta, Diego; Uccelli, Antonio

doi:10.1101/2021.12.23.21268177

Cited by 13 publications

(19 citation statements)

References 17 publications

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“…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%

“…Based on phase-III data, the efficacy profiles of different available COVID-19 vaccine types (i.e., mRNA, AV, inactivated, and protein-based) seems to correlate to their anti-S/S1 humoral immunogenicity – both in healthy people 60,61 and pwMS 62 . Head-to-head comparisons of the available COVID-19 vaccines’ humoral immunogenicity among pwMS reveals the superiority of mRNA-1237 over BNT162b2 (both mRNA-based) 20,25,63 – probably due to higher concentrations of active material, BNT162b2 and mRNA-1237 (mRNA) over ChAdOx1 and Ad26.COV2 (AV) 17,23,29,49 and BNT162b2 (mRNA) over CoronaVac (inactivated) 22 – although humoral immunization did not differ significantly in pwMS on aCD20 receiving BNT162b2 and CoronaVac in Ozakbas et al 22 study.…”

Section: Resultsmentioning

confidence: 99%

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

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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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.

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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 99%

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

Etemadifar

Nouri

Pitzalis

et al. 2022

Preprint

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“…However, we must consider that this result can be confounded by an increased propensity of clinician to admit to hospital pwMS on ocrelizumab who develop Covid-19, because of previous studies showing that these patients are at a higher risk for a severe course 8 . Second, as expected 9 , the vaccine-induced protection from the disease is waning with time since vaccination, and this is more evident in patients treated with DMTs other than ocrelizumab and fingolimod, who already had low antibody levels soon after the vaccination. In fact, while the infection rate is similar in the first and in the second four months after vaccination in patients on ocrelizumab and fingolimod, and consistently higher than in patients on other DMTs, the initial protective effect is vanishing with time for patients in the other DMTs group, who had a good level of antibody response four weeks after vaccination 1 .…”

Section: Discussionmentioning

confidence: 62%

“…Against this background and taking advantage of the large network of MS centers within the Italian Alliance against Covid-19 promoted by the Italian MS Society, we collected data from 27 Italian MS centers on the number of vaccinated patients and the number of patients who had a breakthrough infection in each DMT group, in the period preceding the spread of the Omicron variant, that started its massive diffusion in Italy after the December 2021 holiday season. Aim of this study is to estimate the rate of breakthrough infections per DMT class on a large sample of vaccinated pwMS and to compare the rates of severe infections to the rate observed in Italy in the pre-vaccination era 9 .…”

Section: Introductionmentioning

confidence: 99%

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

Schiavetti

Cordioli

Stromillo

et al. 2022

Preprint

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Background. Patients with Multiple Sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different Disease Modifying Therapy (DMT). Methods. Data on number of vaccinated patients and of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Findings. 19641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. As compared to the other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, RR=3.55,95%CI=2.74-4.58, p<0.001) and fingolimod (0.58% vs 1.62%, RR=2.65,95%CI=1.75-4.00, p<0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% vs 19.4% in the pre-vaccination era (RR=0.86,p=0.74) and it was 3.9% in all the other DMT groups vs 11.9% in the pre-vaccination period (RR=0.33,p=0.02). Interpretation. The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.

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“…This issue is of crucial value given the documented hindering effect of some DMTs—namely sphingosine 1-phosphate receptor (S1PR) modulators and anti-CD20 therapies (aCD20) – on proper immunization against COVID-19. 20 , 21–27 Accordingly, the limited available evidence pointed toward lower clinical efficacy of mRNA 28 and BBIBP-CorV 29 vaccines in pwMS on S1PR modulators and aCD20, however, further replications are required to validate these findings.…”

Section: Discussionmentioning

confidence: 99%

Self-Reported safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among Iranian people with multiple sclerosis

Etemadifar

Abhari

Nouri

et al. 2022

Human Vaccines & Immunotherapeutics

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To affirm the short-term safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among people with multiple sclerosis (pwMS), 517 vaccinated and 174 unvaccinated pwMS were interviewed. 16.2% of the vaccinated pwMS reported at least one neurological symptom in their respective vaccine-related at-risk periods (ARP) – a period from the first dose until two weeks after the second dose of the vaccine. In a multivariable logistic regression model, the presence of comorbidities ( P = 0.01), use of natalizumab ( P = 0.03), and experiencing post-vaccination myalgia ( P < 0.01) predicted the development of post-vaccination neurological symptoms. One MS relapse, one COVID-19 contraction, and one ulcerative colitis flare after the first dose, and four MS relapses after the second dose of the vaccine were the only reported serious adverse events during the ARPs. To show if the vaccine provoked MS relapses, we compared the relapse rate of vaccinated pwMS in the vaccine-related ARP with the annualized relapse rate of unvaccinated pwMS in the prior year—a measure of baseline MS relapsing activity in the respective time—using a multivariable Poisson regression model accounting for possible confounders, which failed to show any statistically significant increase ( P = 0.78). Hence, subject to replication—as the vaccinated and unvaccinated pwMS differed in baseline characteristics—the BBIBP-CorV vaccine does not seem to affect short-term MS activity. Furthermore, as 83.33% of the unvaccinated pwMS reported fear of possible adverse events to be the reason of their vaccination hesitancy, provision of evidence-based consultations to pwMS is encouraged. Limitations of our study briefly included lack of data for self-controlled analysis of relapse rates, possible presence of recall bias, and lack of on-site validations regarding the clinical outcomes due to the remote nature.

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Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies

Cited by 13 publications

References 17 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

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

Self-Reported safety of the BBIBP-CorV (Sinopharm) COVID-19 vaccine among Iranian people with multiple sclerosis

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