key: cord-0929493-8czwuimt
authors: Allen-Philbey, K.; Stennett, A.; Begum, T.; Johnson, AC.; Dobson, R.; Giovannoni, G.; Gnanapavan, S.; Marta, M.; Smets, I.; Turner, B.P.; Baker, D.; Mathews, J.; Schmierer, K.
title: Experience with the COVID-19 AstraZeneca vaccination in people with multiple sclerosis
date: 2021-05-18
journal: Mult Scler Relat Disord
DOI: 10.1016/j.msard.2021.103028
sha: 831dbceacaf5e6364da7f105a340e8a1434966d0
doc_id: 929493
cord_uid: 8czwuimt

BACKGROUND: Some people with multiple sclerosis (pwMS) are at increased risk of severe Coronavirus disease 19 (COVID-19) and should be rapidly vaccinated. However, vaccine supplies are limited, and there are concerns about side-effects, particularly with the ChAdOx1nCoV-19 (AstraZeneca) vaccine. OBJECTIVES: To report our first experience of pwMS receiving the AstraZeneca vaccine. METHODS: Service evaluation. pwMS using the MS service at Barts Health NHS Trust were sent questionnaires to report symptoms following vaccination. RESULTS: Thirty-three responses were returned, 29/33 pwMS received a first dose of AstraZeneca vaccine, the remaining four received a first dose of BioNTech/Pfizer vaccine. All but two patients (94%) reported any symptoms including a sore arm (70%), flu-like symptoms (64%), fever (21%), fatigue (27%), and headache (21%). In more than 2/3 patients, symptoms lasted up to 48 hours, and with the exception of two pwMS reporting symptom duration of 10 and 12 days, respectively, symptoms in the remainder resolved within seven days. No severe adverse effects occurred. CONCLUSIONS: pwMS report transient symptoms following AstraZeneca vaccination, characteristics of which were similar to those reported in the non-MS population. Symptoms may be more pronounced in pwMS due to the temperature-dependent delay in impulse propagation (Uhthoff's phenomenon) due to demyelination.

By the end of April 2021, coronavirus disease 19 (COVID-19) will have killed more than three million people across the Globe. People with disabilities, including those with multiple sclerosis (MS), are at increased risk of severe COVID-19 and death [1] . Treatment with disease-modifying immunotherapy (DMT) may put them at yet higher risk [2] .

The rapid rollout of COVID-19 vaccinations is a key element of public health strategies to suppress the spread of infection [3] . However, concerns about side-effects, particularly AstraZeneca's viral vector vaccine [4] have led to public uncertainty and regulatory suspensions.

Whilst people with MS (pwMS) appear generally not at excess risk from vaccinations [5] , the response to SARS-CoV2 immunization remains unknown, notably in those on DMT.

Our institution (Barts Health NHS Trust) has been heavily involved in the management of people with COVID-19 and research into treatments [6] and vaccines. From January 2021, Barts Health's MS service (BartsMS) fast-tracked pwMS for early vaccination. The majority of pwMS vaccinated through BartsMS received the AstraZeneca vaccine. As part of this rapid access scheme, we asked pwMS to report on their vaccination experience. Two pwMS were on dimethyl-fumarate; five were not on DMT.

All but two patients (94%) reported any symptoms. Among symptoms we specifically inquired about, the following were reported: Sore arm (70%), flu-like symptoms (64%), fever (21%).

In a free text field, the following were described: fatigue (27%), headache (21%), fever/chills (12%), joint pain/muscle ache (9%), nausea (9%), swelling at injection site (6%). One patient each described worsening neurological symptoms, disturbed sleep, facial numbness, urinary tract infection, odd smell/lack of taste, and oral cold sore. In more than 2/3 patients, symptoms did not last longer than 48 hours, and with the exception of one sore arm lasting 10, and one swelling at the injection site lasting 12 days, symptoms in the remaining pwMS resolved within seven days.

To the best of our knowledge, we report the first experience with the AstraZeneca vaccine in pwMS. Given the controversy surrounding this particular vaccine, our results, albeit preliminary, seem reassuring in that adverse events were consistent with those experienced in the general population. Whilst symptoms were unpleasant, affecting all but two pwMS in this small cohort, they resolved in the majority within a couple of days. By day 7, only a small proportion remained symptomatic. Symptoms themselves were commensurate with expectation from both the normal population, and from experience of pwMS with other vaccinations [5] .

Since only four pwMS in our cohort received the BNT162b2 vaccine, no dependable comparisons with the Astra Zeneca vaccine are possible. However, the frequency and characteristics of adverse events with the BNT162b1/BNT162b2 vaccines during the phase 1 trial in the United States resemble those reported in our cohort [7] . The majority of symptoms resolved within seven days of vaccine administration matching the experience in our small cohort. Recently, a significantly lower frequency of adverse events has been reported with the BNT162b2 vaccine in pwMS [8] . Whilst data in that study were collected during consultations in clinic, we relied on the return of multiple-choice questionnaires, which inevitably affects the denominator since patients having an adverse experience are more likely to voice their MSARD-S-21-00644-R1 -Allen-Philbey K, et al. SARS-CoV2 vaccination in multiple sclerosis 6 grievances and, thus, return their questionnaire, than people without, or only minor, side effects.

Although Uhthoff's phenomenon refers more broadly to exacerbation of symptoms due to demyelination when exposed to excess internal or external heat, it was probably first described in 1927 in the context of immunization. It is thought to result from changes in axonal membrane potentials leading to prolonged inactivation of sodium channels and impulse propagation failure in demyelinated axons [9] . Particularly in pwMS with long disease duration, Uhthoff's phenomenon can lead to significant, however transient, deterioration. We did not observe any lasting neurological sequelae or MS relapse. We will continue to collect questionnaires, also covering the second vaccination dose. A larger number of pwMS will provide granularity about potential variations in in vaccine response based on the type of DMT, and serological responses to vaccination.

Notwithstanding recent reports about thrombotic thrombocytopenia following vaccination with the AstraZeneca [4] and other viral vector vaccine(s) against SARS-CoV2 [10] , and the resulting need to observe respective regulatory restrictions and local guidelines, our preliminary experience suggests SARS-CoV2 vaccination is a relatively safe intervention that should be encouraged to protect pwMS and to bring the pandemic under control.

KAP, AS, TB and ACJ have nothing to disclose. RD has received research support from Biogen, Merck, and Celgene, and honoraria/meeting support from Biogen, Merck, Roche,

SARS-CoV2 vaccination in multiple sclerosis References

Outcomes and Risk Factors Associated With SARS-CoV-2

Infection in a North American Registry of Patients With Multiple Sclerosis

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

What policy makers need to know about COVID-19 protective immunity

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

Protecting people with multiple sclerosis through vaccination

RECOVERY trial: the UK covid-19 study resetting expectations for clinical trials

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

COVID-19 vaccination in patients with multiple sclerosis: What we have learnt by

Acute temperature sensitivity in optic nerve axons explained by an electrogenic membrane potential

Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination