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Open accessJournal ArticleDOI: 10.3390/VACCINES9030219

COVID-19 Vaccine Failure in a Patient with Multiple Sclerosis on Ocrelizumab.

04 Mar 2021-Vaccine (Multidisciplinary Digital Publishing Institute)-Vol. 9, Iss: 3, pp 219
Abstract: Vaccines will play a key role in ending the COVID-19 pandemic. Vaccination against infections remains an important part of the management of patients with multiple sclerosis. However, there are limited data about the safety and efficacy of the currently available COVID-19 mRNA vaccines in patients with multiple sclerosis receiving concurrent immunosuppressive therapies. Patients on B cell depleting therapy such as ocrelizumab have an attenuated vaccine response. We report the first case of COVID-19 vaccine failure in a patient with relapsing-remitting multiple sclerosis on B cell depleting therapy, ocrelizumab. We offer suggestions to improve vaccine efficacy in these patients.

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Topics: Ocrelizumab (63%), Vaccine efficacy (61%), Vaccine failure (55%) ... show more
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10 results found


Open accessJournal ArticleDOI: 10.3390/VACCINES9070773
11 Jul 2021-Vaccine
Abstract: Understanding the risks of COVID-19 in patients with Multiple Sclerosis (MS) receiving disease-modifying therapies (DMTs) and their immune reactions is vital to analyze vaccine response dynamics. A systematic review on COVID-19 course and outcomes in patients receiving different DMTs was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Emerging data on SARS-CoV-2 vaccines was used to elaborate recommendations. Data from 4417 patients suggest that MS per se do not portend a higher risk of severe COVID-19. As for the general population, advanced age, comorbidities, and higher disability significantly impact COVID-19 outcomes. Most DMTs have a negligible influence on COVID-19 incidence and outcome, while for those causing severe lymphopenia and hypogammaglobulinemia, such as anti-CD20 therapies, there might be a tendency of increased hospitalization, worse outcomes and a higher risk of re-infection. Blunted immune responses have been reported for many DMTs, with vaccination implications. Clinical evidence does not support an increased risk of MS relapse or vaccination failure, but vaccination timing needs to be individually tailored. For cladribine and alemtuzumab, it is recommended to wait 3-6 months after the last cycle until vaccination. For the general anti-CD20 therapies, vaccination must be deferred toward the end of the cycle and the next dose administered at least 4-6 weeks after completing vaccination. Serological status after vaccination is highly encouraged. Growing clinical evidence and continuous surveillance are extremely important to continue guiding future treatment strategies and vaccination protocols.

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Topics: Vaccination (53%), Population (51%)

4 Citations


Open accessJournal ArticleDOI: 10.1016/J.INTIMP.2021.108021
Abstract: Since the beginning of vaccination programs against COVID-19 in different countries, several populations such as patients with specific immunological conditions have been considered as the priorities for immunization. In this regard, patients with autoimmune diseases or those receiving immunosuppressive agents and anti-cancer therapies, need special attention. However, no confirmed data is presently available regarding COVID-19 vaccines in these populations due to exclusion from the conducted clinical trials. Given the probable suppression or over-activation of the immune system in such patients, reaching a consensus for their vaccination is critical, besides gathering data and conducting trials, which could probably clarify this matter in the future. In this review, besides a brief on the available COVID-19 vaccines, considerations and available knowledge about administering similar vaccines in patients with cancer, hematopoietic stem cell transplantation, solid organ transplantation, multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatologic and dermatologic autoimmune disorders are summarized to help in decision making. As discussed, live-attenuated viruses, which should be avoided in these groups, are not employed in the present COVID-19 vaccines. Thus, the main concern regarding efficacy could be met using a potent COVID-19 vaccine. Moreover, the vaccination timing for maximum efficacy could be decided according to the patient's condition, indicated medications, and the guides provided here. Post-vaccination monitoring is also advised to ensure an adequate immune response. Further studies in this area are urgently warranted.

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Topics: Transplantation (55%), Vaccination (53%)

4 Citations


Open accessJournal ArticleDOI: 10.3389/FNEUR.2021.721502
Abstract: We describe a case of acute relapse in a woman with Multiple Sclerosis (MS) shortly after the mRNA COVID-19 vaccination. The patient received a diagnosis of MS in November 2016 at the MS Centre of the A. Cardarelli Hospital (South of Italy). Since that moment, her clinical conditions and pharmacological therapies have been managed at this MS centre where, according to national recommendations, in April 2021, the patient received the BNT162b2 vaccine. Almost 48 h after receiving the vaccine, the patient developed paraesthesia and weakness in her left arm and limbs. The neurological examination revealed walking difficulties while the MRI showed three new voluminous enhancing lesions. After having received methylprednisolone iv for 5 days, the patient's neurological symptoms fully recovered. Along with the implementation of COVID-19 vaccination programmes among vulnerable population, further studies are needed in order to improve our knowledge on the benefit/risk ratio of COVID-19 vaccines.

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Topics: Neurological examination (52%)

4 Citations



Open accessJournal ArticleDOI: 10.3389/FIMMU.2021.701752
Abstract: For more than a year now, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been causing the coronavirus disease (COVID-19) pandemic with high mortality and detrimental effects on society, economy, and individual lives. Great hopes are being placed on vaccination as one of the most potent escape strategies from the pandemic and multiple vaccines are already in clinical use. However, there is still a lot of insecurity about the safety and efficacy of vaccines in patients with autoimmune diseases like multiple sclerosis (MS), especially under treatment with immunomodulatory or immunosuppressive drugs. We propose strategic approaches to SARS-CoV-2 vaccination management in MS patients and encourage fellow physicians to measure the immune response in their patients. Notably, both humoral and cellular responses should be considered since the immunological equivalent for protection from SARS-CoV-2 after infection or vaccination still remains undefined and will most likely involve antiviral cellular immunity. It is important to gain insights into the vaccine response of immunocompromised patients in order to be able to deduce sensible strategies for vaccination in the future.

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Topics: Vaccination (57%), Cellular immunity (55%)

2 Citations


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7 results found


Open accessJournal ArticleDOI: 10.1056/NEJMOA2034577
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

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4,222 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA2035389
Abstract: Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

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Topics: Vaccine efficacy (62%), Breakthrough infection (53%), Placebo (50%)

2,721 Citations


Open accessJournal ArticleDOI: 10.1056/NEJMOA1601277
Stephen L. Hauser1, Amit Bar-Or2, Giancarlo Comi3, Gavin Giovannoni4  +17 moreInstitutions (15)
Abstract: BackgroundB cells influence the pathogenesis of multiple sclerosis. Ocrelizumab is a humanized monoclonal antibody that selectively depletes CD20+ B cells. MethodsIn two identical phase 3 trials, we randomly assigned 821 and 835 patients with relapsing multiple sclerosis to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or subcutaneous interferon beta-1a at a dose of 44 μg three times weekly for 96 weeks. The primary end point was the annualized relapse rate. ResultsThe annualized relapse rate was lower with ocrelizumab than with interferon beta-1a in trial 1 (0.16 vs. 0.29; 46% lower rate with ocrelizumab; P<0.001) and in trial 2 (0.16 vs. 0.29; 47% lower rate; P<0.001). In prespecified pooled analyses, the percentage of patients with disability progression confirmed at 12 weeks was significantly lower with ocrelizumab than with interferon beta-1a (9.1% vs. 13.6%; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.81; P<0.001), as was the percentage of patients with disabilit...

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Topics: Ocrelizumab (66%), Interferon beta-1a (62%)

850 Citations


Open accessJournal ArticleDOI: 10.1001/JAMANEUROL.2020.2581
Céline Louapre1, Nicolas Collongues1, B. Stankoff1, C. Giannesini  +16 moreInstitutions (2)
01 Sep 2020-JAMA Neurology
Abstract: Importance Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities Objective To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity Design, Setting, and Participants The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Societe Francophone de la Sclerose en Plaques The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020 Exposures COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms Main Outcomes and Measures The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen) We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes Results A total of 347 patients (mean [SD] age, 446 [128] years, 249 women; mean [SD] disease duration, 135 [100] years) were analyzed Seventy-three patients (210%) had a COVID-19 severity score of 3 or more, and 12 patients (35%) died of COVID-19 The median EDSS was 20 (range, 0-95), and 284 patients (818%) were receiving DMT There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (460% vs 155%;P Conclusions and Relevance In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic

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216 Citations


Open accessJournal ArticleDOI: 10.1212/WNL.0000000000010380
Amit Bar-Or1, Jonathan Calkwood1, Cathy Chognot1, Joanna Evershed1  +9 moreInstitutions (1)
06 Oct 2020-Neurology
Abstract: Objective The phase IIIb A Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Participants With Relapsing Forms of Multiple Sclerosis (VELOCE) study (NCT02545868) assessed responses to selected vaccines in ocrelizumab (OCR)-treated patients with relapsing multiple sclerosis. Methods Patients were randomized 2:1 into the OCR group (n = 68; OCR 600 mg) or control group (n = 34; interferon beta or no disease-modifying therapy). All received tetanus toxoid (TT)-containing vaccine, Pneumovax (23-valent pneumococcal polysaccharide vaccine [23-PPV]), and keyhole limpet hemocyanin (KLH). The OCR group was subdivided into OCR1 (n = 33) and OCR2 (n = 35) at randomization. The OCR1 group received Prevnar (13-valent conjugate pneumococcal vaccine) 4 weeks after 23-PPV; the OCR2 and control groups received influenza vaccine. Vaccinations started 12 weeks after OCR initiation (OCR group) or on day 1 (control group). Results Positive response rate to TT vaccine at 8 weeks was 23.9% in the OCR vs 54.5% in the control group. Positive response rate to ≥5 serotypes in 23-PPV at 4 weeks was 71.6% in the OCR and 100% in the control group. Prevnar did not enhance response to pneumococcal serotypes in common with Pneumovax. Humoral response to KLH was decreased in the OCR vs control group. Seroprotection rates at 4 weeks against 5 influenza strains ranged from 55.6% to 80.0% in the OCR2 group and 75.0% to 97.0% in the control group. Conclusion Peripherally B-cell–depleted OCR recipients mounted attenuated humoral responses to clinically relevant vaccines and the neoantigen KLH, suggesting that use of standard nonlive vaccines while on OCR treatment remains a consideration. For seasonal influenza vaccines, it is recommended to vaccinate patients on OCR because a potentially protective humoral response, even if attenuated, can be expected. Classification of evidence This study provides Class II evidence confirming that the humoral response to nonlive vaccines in patients with relapsing multiple sclerosis after OCR treatment is attenuated compared with untreated or interferon beta–treated patients, but they can still be expected to be protective. Clinicaltrials.gov identifier NCT02545868.

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Topics: Pneumococcal vaccine (57%), Pneumococcal polysaccharide vaccine (55%), Influenza vaccine (53%) ... show more

149 Citations


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