Informing patients about their potential coronavirus risks associated with anti-CD20 therapy is complicated and resulting in our patients being given different advice depending on who they see. The reason for this is that we don’t have the direct evidence to be able to dissect out why people on anti-CD20 therapy are at higher risk of COVID-19 and at higher risk of being admitted to hospital with severe COVID-19.
I doubt this increased risk relates to increased exposure to the coronavirus. Why should someone on ocrelizumab who attends their healthcare facility be at increased risk of acquiring SARS-CoV-2 infection compared to someone for example on natalizumab who attends for their infusion every 4-6 weeks?
The clue to the increased risk is in the detail of the data. It is apparent that the longer you have been on an anti-CD20 therapy the greater your risk; the risk of COVID-19 is particularly high if you have been on an anti-CD20 therapy for more than 3 years. This means that it must be due to prior exposures, i.e. exposures before the COVID-19 pandemic started.
In the general population, it is now clear that some people have T-cells and antibodies that cross-react with SARS-CoV-2 and that these protect these people from developing COVID-19 or severe COVID-19. These cross-reactive immune responses are likely to have developed in response to infection or exposure to other circulating coronaviruses; the viruses that cause the common cold.
My theory is that if you are on an anti-CD20 therapy with no B-cells and a poorly functioning antibody response and you get the common cold your immune system will not be able to make these protective cross-reactive anti-coronavirus antibodies. This would then reduce your chances of being protected from getting COVID-19 or getting only mild COVID-19 when you are infected with SARS-CoV-2.
I have tried to illustrate this in the following slide showing that people on long-term anti-CD20 therapies are more likely to get symptomatic SARS-CoV-2 infection, i.e. COVID-19, and when they do get COVID-19 it is likely to be more severe. Severity in this context is requiring hospitalisation and potential intensive care and ventilation.
What does this mean for you? It means that if you are about to start ocrelizumab, rituximab or ofatumumab then your chances of getting COVID-19 are unlikely to be different to another DMT, with the exception of interferon-beta that lowers your risk because of its antiviral effects.
If you happen to be on ocrelizumab, rituximab or ofatumumab already there is little you can do, because these agents are not rapidly reversible and even if you stop the treatment and allow your B-cell compartment to reconstitute you are unlikely to develop the cross-reactive immunity from common coronaviruses. However, by stopping your anti-CD20 and allowing your B-cells to reconstitute you will be allowing your immune system to prepare itself for a coronavirus vaccine in the future.
At the beginning of the pandemic, I was a bit cynical about the chances of a successful coronavirus vaccine emerging, but the preliminary phase 2 results of several vaccines and the immunological insights above have made me much more optimistic that we will have an effective coronavirus vaccine quite soon. When I say soon I suspect we will have one ready for general consumption early next year. In all likelihood, one of the first vaccines will be the Oxford-AstraZeneca vaccine that happens to involve a live virus, which itself will have implications for some of the MS DMTs.
If my predictions are correct the MS community may need to start getting vaccine ready or they can simply rely on herd immunity. With anti-CD20 therapy, this needs to be planned ahead and patients will need to miss one, two or possibly three infusions depending on their body size and individual B-cell reconstitution kinetics in order to prepare their immune systems for the vaccine.
Some critics of this strategy are saying that patients on an anti-CD20 therapy will still make T-cell responses to the vaccine that will in all likelihood protect them. Yes, this may be the case, but then how do you explain the above observations that people on anti-CD20 therapy are at increased risk of COVID-19 and severe COVID-19? I would interpret this as them having blunted T-cell responses to cross-reactive common coronaviruses. If this is the case pwMS on an anti-CD20 will have blunted T-cell response to the vaccine. In support of the latter is the observation that several pwMS on ocrelizumab who have had swab-positive COVID-19 have failed to make an antibody response to the virus. Please remember that good quality antibody responses are T-cell dependent. These observations are telling me that in all likelihood being on anti-CD20 therapy will prevent you from developing protective immunity to coronavirus from a vaccine.
Clearly getting more detailed population-level COVID-19 data in people with MS is very important. This is why we are trying to crowdfund our study to identify people who have antibodies to SARS-CoV-2. We will be able to use this resource to do nested immunological studies on pwMS on different DMTs to understand the cross-reactive immunology at both the T and B cell level to coronaviruses in general and test the hypotheses above. It will also allow us to study vaccine responses if and when the vaccines arrive.
If you are prepared to help with a small donation it would be much appreciated. Thank you.