Humoral immune response in multiple sclerosis patients following PfizerBNT162b2 COVID19 vaccination: Up to 6 months cross-sectional study

Achiron, Anat; Mandel, Mathilda; Dreyer-Alster, Sapir; Harari, Gil; Dolev, Mark; Menascu, Shay; Magalashvili, David; Flechter, Shlomo; Givon, Uri; Guber, Diana; Sonis, Polina; Zilkha‐Falb, Rina; Gurevich, Michael

doi:10.1016/j.jneuroim.2021.577746

Cited by 68 publications

(110 citation statements)

References 16 publications

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“…The results of this study confirm and expand previous studies [1][2][3] by showing that pwMS on NTZ develop and maintain a 6-month humoral response after the first dose of a full COVID-19 vaccination cycle comparable to their healthy peers; moreover, we found that, in pwMS on NTZ, higher physical disability is associated with a lower humoral response over time. These findings are relevant for clinicians called to counsel about COVID-19 mRNA vaccine timing and booster doses in pwMS treated with NTZ.…”

Section: Discussionsupporting

confidence: 90%

“…In the first short-term study on pwMS on NTZ [1], in which levels of IgG antibodies to SARS-CoV-2 spike protein (anti-TSP IgG) were evaluated in 31 pwMS 7 days after the second dose of the BNT162b2 mRNA vaccine, the authors reported an efficient humoral response, with values comparable to those of age-and sex-matched healthy controls (HCs). In another cross-sectional study evaluating the humoral response ~ 3 months after the second BNT162b2 mRNA vaccine dose in 32 pwMS treated with NTZ, a positive humoral response was measured in all pwMS, with no significant differences on levels of anti-TSP IgG between the NTZ and HC groups [2]. A third study on a larger population of 100 pwMS on NTZ confirmed that 4 weeks after the second dose of a mRNA vaccine (BNT162b2 or mRNA-1273), all participants mounted a full humoral response [3].…”

Section: Introductionmentioning

confidence: 98%

“…Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) on natalizumab (NTZ) [1][2][3], a high-efficacy diseasemodifying therapy (DMT) that binds to α4β1-integrin and inhibits migration of leukocytes into the central nervous system, thus halting inflammatory activity typical of MS [4,5]. In the first short-term study on pwMS on NTZ [1], in which levels of IgG antibodies to SARS-CoV-2 spike protein (anti-TSP IgG) were evaluated in 31 pwMS 7 days after the second dose of the BNT162b2 mRNA vaccine, the authors reported an efficient humoral response, with values comparable to those of age-and sex-matched healthy controls (HCs).…”

Section: Introductionmentioning

confidence: 99%

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Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab

et al. 2022

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Background Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient humoral response; however, there are no studies assessing the levels of SARS-CoV-2 IgG antibodies in pwMS treated with NTZ over time. Methods Humoral immune response to BNT162b2 mRNA COVID-19 vaccine was assessed in a group of 26 pwMS on NTZ up to 6 months after a full COVID-19 vaccination cycle and compared it with 43 age-and sex-matched group of HC. Serum samples were collected before the first dose (T0), and 4 weeks (T1) and 6 months (T2) after the first dose of BNT162b2 mRNA COVID-19 vaccine. The LIAISON® SARS-CoV-2 TrimericS-IgG assay (DiaSorin-S.p.A.) was employed for the detection of IgG antibodies to SARS-CoV-2 spike protein (cutoff for positive IgG antibodies: 33.8 BAU/mL). Results At T1 and T2, both groups showed an efficient humoral response to BNT162b2 mRNA COVID-19 vaccine. A significant reduction of IgG antibodies to SARS-CoV-2 spike protein was detected at T2 both in pwMS and in HC, but SARS-CoV-2 IgG antibodies were still above the cutoff limit in all participants. Conclusions pwMS on NTZ develop and maintain a long-term humoral response after a full COVID-19 vaccination cycle comparable to their healthy peers, and these findings are relevant for clinicians called to counsel about COVID-19 mRNA vaccine timing and booster doses in pwMS treated with NTZ.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab

et al. 2022

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“…Overall, 82 studies were included for meta-analysis ( table 1 , supplementary table 2). 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 …”

Section: Resultsmentioning

confidence: 99%

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

Lee

Wong

Chai

et al. 2022

BMJ

349

313

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Objective To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. Design Systematic review and meta-analysis. Data sources PubMed, Embase, Central Register of Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), and WHO covid-19 databases for studies published between 1 December 2020 and 5 November 2021. ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched in November 2021 to identify registered but as yet unpublished or ongoing studies. Study selection Prospective observational studies comparing the efficacy of covid-19 vaccination in immunocompromised and immunocompetent participants. Methods A frequentist random effects meta-analysis was used to separately pool relative and absolute risks of seroconversion after the first and second doses of a covid-19 vaccine. Systematic review without meta-analysis of SARS-CoV-2 antibody titre levels was performed after first, second, and third vaccine doses and the seroconversion rate after a third dose. Risk of bias and certainty of evidence were assessed. Results 82 studies were included in the meta-analysis. Of these studies, 77 (94%) used mRNA vaccines, 16 (20%) viral vector vaccines, and 4 (5%) inactivated whole virus vaccines. 63 studies were assessed to be at low risk of bias and 19 at moderate risk of bias. After one vaccine dose, seroconversion was about half as likely in patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 to 0.50, I 2 =80%; absolute risk 0.29, 95% confidence interval 0.20 to 0.40, I 2 =89%), immune mediated inflammatory disorders (0.53, 0.39 to 0.71, I 2 =89%; 0.29, 0.11 to 0.58, I 2 =97%), and solid cancers (0.55, 0.46 to 0.65, I 2 =78%; 0.44, 0.36 to 0.53, I 2 =84%) compared with immunocompetent controls, whereas organ transplant recipients were 16 times less likely to seroconvert (0.06, 0.04 to 0.09, I 2 =0%; 0.06, 0.04 to 0.08, I 2 =0%). After a second dose, seroconversion remained least likely in transplant recipients (0.39, 0.32 to 0.46, I 2 =92%; 0.35, 0.26 to 0.46), with only a third achieving seroconversion. Seroconversion was increasingly likely in patients with haematological cancers (0.63, 0.57 to 0.69, I 2 =88%; 0.62, 0.54 to 0.70, I 2 =90%), immune mediated inflammatory disorders (0.75, 0.69 to 0.82, I 2 =92%; 0.77, 0.66 to 0.85, I 2 =93%), and solid cancers (0.90, 0.88 to 0.93, I 2 =51%; 0.89, 0.86 to 0.91, I 2 =49%). Seroconversion was similar between people with HIV and immunocompetent controls (1.00, 0.98 to 1.01, I 2 =0%; 0.97, 0.83 to 1.00, I 2 =89%). Systematic review of 11 studies showed that a third dose of a covid-19 mRNA vaccine was associated with seroconversion among vaccine non-responders with solid cancers, haematological cancers, and immune mediated inflammatory disorders, although response was variable in transplant recipients and inadequately studied in people with HIV and those receiving non-mRNA vaccines. Conclusion Seroconversion rates after covid-19 vaccination were significantly lower in immunocompromised patients, especially organ transplant recipients. A second dose was associated with consistently improved seroconversion across all patient groups, albeit at a lower magnitude for organ transplant recipients. Targeted interventions for immunocompromised patients, including a third (booster) dose, should be performed. Systematic review registration PROSPERO CRD42021272088.

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“…There are cumulative data reporting that MS patients treated with fingolimod failed to develop humoral as well as cellular immune responses due to low lymphocyte counts and thus are not protected from COVID-19 infection [ 5 – 7 ]. A significant decrease in the antibody level was associated with the presence and degree of lymphopenia [ 8 , 9 ]. Inability to achieve immune protection can have deleterious effects for patients as they are at a greater risk of COVID-19 infection, need to preserve social distance and avoid social interactions that can lead to increased psychological stress [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod

et al. 2022

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Background The majority of multiple sclerosis [MS] patients treated with fingolimod fail to develop a protective level of IgG humoral and adaptive cellular immune responses following full BNT162b2 SARS-CoV-2 vaccination. Objective To compare the efficacy of the third COVID-19 vaccine dose in vaccine non-responders fingolimod-treated MS patients. Study design This is a prospective 3-month, single-center, randomized clinical trial. Methods Twenty relapsing MS patients who had been on fingolimod therapy ≥ 12 months and failed to develop humoral IgG immune response to 2-dose Pfizer BNT162b2 COVID-19 vaccination were randomized into two groups: fingolimod-continuation group and fingolimod-discontinuation group. Humoral and memory cellular immune responses were assessed within 1 and 3 months following the third Pfizer BNT162b2 vaccine dose and compared between the groups. Results A higher rate of patients in the fingolimod-discontinuation group [ n = 8/10] compared to fingolimod-continuation group [ n = 2/10] developed positive SARS-COV-2 IgG. Median IgG titer 1 month following the third dose was 202.3 BAU/ml vs. 26.4 BAU/ml, respectively, p = 0.022. The development of IgG humoral response correlated with absolute lymphocyte count. Specific SARS-COV-2 memory B cell and T cell immune responses were not detected in both groups, either at 1 month or 3 months following the third COVID-19 vaccine dose. Conclusions Short period of fingolimod treatment discontinuation was associated with the development of humoral protection but not with adaptive cellular immunity. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-022-11030-0.

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Humoral immune response in multiple sclerosis patients following PfizerBNT162b2 COVID19 vaccination: Up to 6 months cross-sectional study

Cited by 68 publications

References 16 publications

Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab

Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab

Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

Immune response to the third COVID-19 vaccine dose is related to lymphocyte count in multiple sclerosis patients treated with fingolimod

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