Covid-19 Vaccine Immune Response in Multiple Sclerosis

Study Overview
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Brief Summary
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Coronavirus (Covid-19) has affected millions of people worldwide. Vaccines to prevent Covid-19 infection have been offered to reduce the risk of infection. While these vaccines have been offered to people with multiple sclerosis (MS), they have not been tested in these individuals. It is uncertain whether people with MS will develop protective antibodies after a Covid-19 vaccination and how long these antibodies will last. The investigators are planning to study the immune response to the full course of Covid-19 vaccine in people with MS (study group) and compare this to people without MS or immune suppression (control group).

Official Title
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An Observational Study to Evaluate Immune Response to Covid-19 Vaccines, Infections and Immune Treatments in People With Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: Blood Test 1
* Other: Blood Test 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (Study Group - MS Patients): Aged 18 years and over Diagnosis of Multiple Sclerosis as per McDonald's Criteria 2017 Falls into one of following the Disease Modification Treatment (DMT) groups: on Ocrelizumab, on Natalizumab, on Alemtuzumab, on Tecfidera, on Fingolimod, on Interferon, not on any DMT Has had a complete course of Covid-19 vaccination including any boosters (standard dosing: prescribed as per the UK Government guidelines) Willing and able to give fully informed consent Willing and able to comply with the study procedures Exclusion Criteria (Study Group - MS Patients): Has declined or does not wish to have Covid-19 vaccine Has switched DMT since the date of first dose of Covid-19 vaccine Has any other immunological condition or on immune treatment causing immune suppression Has declined or does not wish to have Covid-19 vaccine Ineligible* for Covid-19 vaccine (*Ineligible for health reasons and/or as per Government prioritisation of vaccinations) Non-English speaker where translation facilities are insufficient to guarantee informed consent Inclusion Criteria (Control Group - Healthy Volunteers): Aged 18 years and over Has had a complete course of Covid-19 vaccination (standard dosing: prescribed as per the UK Government guidelines) Willing and able to give fully informed consent Willing and able to comply with the study procedures Exclusion Criteria (Control Group - Healthy Volunteers): Has declined or does not wish to have Covid-19 vaccine Has MS or another long-term immunological condition History of taking any immune treatment causing immune suppression in the last 5 years History of any immune conditions or comorbidities known to result in immune suppression within the last 5 years; Ineligible* for Covid-19 vaccine (*Ineligible for health reasons and/or as per Government prioritisation of vaccinations) Currently participating in one or more interventional trials involving immune suppression or immune agent Non-English speaker where translation facilities are insufficient to guarantee informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study group - Ocrelizumab<br>30 patients with multiple sclerosis on Ocrelizumab (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Study group - Natalizumab<br>30 patients with multiple sclerosis on Natalizumab (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Study group - Alemtuzumab<br>30 patients with multiple sclerosis on Alemtuzumab (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Study group - Tecfidera<br>30 patients with multiple sclerosis on Tecfidera (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Study group - Fingolimod<br>30 patients with multiple sclerosis on Fingolimod (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Study group - Interferon<br>30 patients with multiple sclerosis on Interferon (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Study group - off DMT<br>30 patients with multiple sclerosis off disease modification treatment (DMT) (standard of care) | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|
| Control group<br>30 healthy volunteers | Other: Blood Test 1<br>* Blood test 1 - At 12 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>Other: Blood Test 2<br>* Blood test 2 - At 18 months (+3months) from the date of 1st Covid-19 vaccine: Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche, T-SPOT® COVID SARS-CoV-2, Full Blood Count, Serum Immunoglobulins, Anti-VZV titres<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood titres of Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche in MS patients compared with healthy volunteers 12 months from date of first dose of Covid-19 vaccine | Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Blood titres of Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche in MS patients compared with healthy volunteers 18 months from date of first dose of Covid-19 vaccine | Anti-SARS-CoV-2 S1/S2/N IgG antibody Roche | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 
| T-SPOT® COVID SARS-CoV-2 test status in MS patients compared with healthy volunteers 12 months from date of first dose of Covid-19 vaccine | T-SPOT® COVID SARS-CoV-2 test status | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| T-SPOT® COVID SARS-CoV-2 test status in MS patients compared with healthy volunteers 18 months from date of first dose of Covid-19 vaccine | T-SPOT® COVID SARS-CoV-2 test status | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Type and timing of DMT in MS patients | Type and timing of DMT | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Type and timing of DMT in MS patients | Type and timing of DMT | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Type and timing of Covid-19 vaccine in MS patients compared with healthy volunteers | Type and timing of Covid-19 vaccine | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Type and timing of Covid-19 vaccine in MS patients compared with healthy volunteers | Type and timing of Covid-19 vaccine | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Participant-reported PCR positive Covid-19 infection/s in MS patients compared with healthy volunteers | Participant-reported PCR positive Covid-19 infection/s | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Participant-reported PCR positive Covid-19 infection/s in MS patients compared with healthy volunteers | Participant-reported PCR positive Covid-19 infection/s | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Covid-19 vaccine-related serious adverse events in MS patients compared with healthy volunteers | Vaccine-related serious adverse events | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Covid-19 vaccine-related serious adverse events in MS patients compared with healthy volunteers | Vaccine-related serious adverse events | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Demographics of MS patients compared with healthy volunteers | Demographics | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Demographics of MS patients compared with healthy volunteers | Demographics | 18 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Co-morbidity status of MS patients compared with healthy volunteers | Co-morbidity status | 12 months (+3 months) from date of first dose of Covid-19 vaccine | 
| Co-morbidity status of MS patients compared with healthy volunteers | Co-morbidity status | 18 months (+3 months) from date of first dose of Covid-19 vaccine |