Anti-CD20 therapy not only increases your chances of getting COVID-19 but also increases your chances of developing severe COVID-19 and having to be admitted to hospital for treatment. I have argued that the likely mechanism is to be due to anti-CD20 therapies blunting important cross-reactive anti-coronavirus immune response acquired from other community-acquired coronaviruses. If this is correct it means that people with MS (pwMS), and other diseases, on anti-CD20 therapies, will be unlikely to mount protective immune responses to ane effective SARS-CoV-2 vaccine.
Based on the questions I have been asked on social media and recent COVID-19 related webinars vaccine readiness is clearly playing on the minds of many HCPs and pwMS. To provide some perspective we have recently written a review paper on vaccine readiness to highlight this topic and to how to mitigate this issue.
It seems likely that pwMS on anti-CD20 therapies are going to have to take a drug holiday to allow peripheral blood B-cell reconstitution before being vaccinated. What I don’t know is whether or not this hypothesis is correct and if correct what level of B-reconstitution will be necessary to allow an adequate vaccine response. I, therefore, propose testing this in a clinical trial where we compare antibody and T-cell responses to the SARS-CoV-2 vaccine when it emerges with different levels of peripheral B-cell reconstitution. The idea will be to vaccinate patients at different time points after early and late (above normal) peripheral blood B-cell reconstitution. I have called this trial the COVAX Study or the “Coronavirus Ocrelizumab VA(X)ccination Study”.
If you are on ocrelizumab would you volunteer to participate in this study?
Baker et al. COVID-19 vaccine-readiness for ocrelizumab and other anti-CD20-depleting therapies in multiple sclerosis and other autoimmune diseases. Authorea. June 23, 2020. DOI: 10.22541/au.159292858.82650822
Although most autoimmune diseases are considered to be CD4 T-cell or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab that is used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities, notably multiple sclerosis, where ofatumumab is in late stage development and ocrelizumab is approved for use. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of multiple sclerosis and COVID-19, it was hypothesised that whilst B-cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B-cell subset inhibition that controls multiple sclerosis and other autoimmunities, would not influence innate and CD8 T-cell responses, which are central to SARS-CoV-2 elimination, nor the hyper-coagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority (mortality rate n=~5/392) of SARS-CoV-2 infected, CD20-depleted people with multiple sclerosis have recovered. However, protective neutralising-antibody and vaccination responses are predicted to be blunted, until naïve B-cells repopulate, based on B-cell repopulation-kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose-interruption to maintain inflammatory disease control in MS and other autoimmune diseases, whilst allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available.