Covid-19 Vaccine Immune Response in Multiple Sclerosis (CoVaR-MS)

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Blood Test 1; Other: Blood Test 2

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

Study Locations

• United Kingdom
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • University Hospitals of North Midlands NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

There are two groups of participants in this study:

1. Multiple Sclerosis Patients (Study Group): 210 patients with multiple sclerosis, on and off disease modification treatment (DMT):

   • 180 patients on DMT, divided as follows: 30 patients on Ocrelizumab, 30 patients on Natalizumab, 30 patients on Alemtuzumab, 30 patients on Tecfidera, 30 patients on Fingolimod, 30 patients on Interferon
   • 30 patients off DMT
2. Healthy Volunteers (Control Group): 30 healthy volunteers

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

8

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group - Ocrelizumab; 30 patients with multiple sclerosis on Ocrelizumab (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Study group - Natalizumab; 30 patients with multiple sclerosis on Natalizumab (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Study group - Alemtuzumab; 30 patients with multiple sclerosis on Alemtuzumab (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Study group - Tecfidera; 30 patients with multiple sclerosis on Tecfidera (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Study group - Fingolimod; 30 patients with multiple sclerosis on Fingolimod (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Study group - Interferon; 30 patients with multiple sclerosis on Interferon (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Study group - off DMT; 30 patients with multiple sclerosis off disease modification treatment (DMT) (standard of care)	Other: Blood Test 1; 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; Other: Blood Test 2; 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
Control group; 30 healthy volunteers	Other: Blood Test 1; 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; Other: Blood Test 2; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospitals of North Midlands NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Actual): December 30, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: March 2, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 3, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 3200

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No