COVID-19: are booster vaccines necessary?

It is clear that the SARS-CoV-2 delta variant is a partial vaccine escape variant. This means that people with MS who have been vaccinated in the past are likely to need a booster.

Apologies about another Newsletter I am trying not to send them out daily. However, it is important for you to be aware of the rather alarming new COVID-19 data emerging across the world, but particularly in Israel. 

The majority of Israel’s older population have received two doses of the Pfizer-BioNTech RNA vaccine with 78% of the population 12 and older being fully vaccinated.  As a result of this Israel got rid of all restrictions in terms of social distancing and masks. Despite so-called herd immunity, Israel is now seeing a spike in new cases of COVID-19 and deaths. The alarming thing is the new cases and deaths are not limited to the unvaccinated but are now being seen in the vaccinated elderly population. 

What does this mean? It means that the new delta SARS-CoV-2 variant that is rampaging through Israel and the rest of the world is more infectious than the original Wuhan/alpha and other beta strains, i.e. it has a higher R-number, it causes more severe disease and it seems to be partially resistant to vaccine immunity. The delta variant is particularly resistant to partial immunity, i.e. from one and not two doses of the vaccine. Another factor, particularly in the elderly population is waning immunity, i.e. with time anti-SARS-CoV-2 antibodies are lost. The implication of this is that booster vaccines will be necessary particularly in the older age groups and vulnerable populations. 

So what has this got to with MS? It is clear that pwMS and related disorders on B-cell depleting therapies such as anti-CD20 (rituximab, ocrelizumab, ofatumumab and ublituximab) and anti-CD19 (inebilizumab) and those on S1P modulators (fingolimod, siponimod, ozanimod and ponesimod) have blunted COVID-19 vaccine responses and hence will be at high risk of getting COVID-19 with the delta variant. Therefore, if you are on one of these treatments you are going to have to remain extra vigilant and avoid high-risk places, e.g. indoor spaces. In addition, you are almost certainly going to require a booster dose of the vaccine. 

Anti-CD20 / Anti-CD19

However, when it comes to the booster it may be appropriate to delay being vaccinated to a point in time when you have some peripheral B-cell reconstitution. This means delaying your next course of anti-CD20 and potentially missing a dose or two to allow your peripheral B-cell counts to recover. It looks like you will need at least 10 CD19+ B-cells/mm3 in the peripheral blood. The problem with this advice is that it is not going to be easy logistically to do. Many MS centres don’t have the time and resources to check B-cell counts, a large number of neurologists will disagree with this advice and neurologists, in general, don’t have control of vaccine supplies. In some countries, if you don’t take up your offer to have a booster vaccine in a specific time window it may be difficult to get vaccinated at a later time point. 

S1P modulators

In relation to the S1P modulators, I would not recommend stopping them to have the vaccine. Stopping these agents will put you at risk of rebound disease activity. So I would suggest just getting the booster vaccine when it is offered and hope for the best. 

Unvaccinated

I am writing this Newsletter assuming you have all been vaccinated. However, I am aware that many of you may not have had access to the vaccine or you may have decided against vaccination on safety grounds. To reiterate,  COVID-19 is orders of magnitude more dangerous than the vaccine. Not to mention the 1 in 10 chance of getting long-COVID after the acute infection. The serious adverse events from the COVID-19 vaccines are rare so in my opinion, the benefits of the COVID-19 vaccine far outweigh the risks of vaccination. If you have not been vaccinated yet I would not delay vaccination. I would recommend getting vaccinated as soon as possible. During the pandemic, some immunity is better than no immunity; the immunity may just be sufficient to prevent you from getting severe COVID-19 or dying from the infection. 

Conclusions

It is clear that this pandemic is far from over and it looks like it will have a long tail. Let’s hope newer variants, i.e those beyond the current delta variant, won’t escape the current vaccine immunity. 

On a positive note, we have learnt so much about COVID-19, vaccine immunology and how MS DMTs interact with both the infection and vaccine responses that we will be in a much better position to manage MS in future pandemics or epidemics. 

Please feel free to ask any questions.

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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general advice and should not be interpreted as being personal clinical advice. If you have problems please tell your own healthcare professional who will be able to help you.