Correspondence: Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies.

Dear Editor,

First of all, we would like to thank Achiron and colleagues for addressing a really urgent topic in their study dealing with the humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis (MS) treated with high-efficacy disease-modifying therapies (DMT). However, although the authors recognize several study limitations and the need to extend their preliminary data, the authors draw conclusions with regard to treatment changes (delay or discontinuation of potent DMT) in patients with MS. In our opinion, this may cause more harm than benefit to MS patients by increasing the risk of recurrent disease activity, especially in the context of discontinuation a DMT with fingolimod.

The data reported by Achiron et al. are somewhat unexpected, and contradict results of previous studies that showed an impaired immune response after vaccination of MS patients under treatment with ocrelizumab and fingolimod.[2,3] Moreover, those latter studies revealed that the patients were clearly able to mount antibodies against de novo and recall antigens after vaccination.[2,3] In line with this finding, another study did show detectable SARS-Cov-2 antibodies after COVID-19 in MS patients under various DMT, including fingolimod.

As the authors mentioned, the small sample size might have had an impact, as well as the study design, focusing on one single time point of antibody measurement with no well defined time-lines. The limited half-life of antibodies of about 21 days may contribute to low, or even undetectable, antibody titers in the respective study arms.

Furthermore, lack of detectable antibody response does not necessarily mean absence of immunity, since innate and adaptive cellular immune responses represent important defence mechanisms; however, this was not addressed in the current study. The immunological memory against SARS-CoV-2 measured to date after approximately 6 months apparently shows no correlation between T-lymphocyte and B-cell responses, and immunity protection is mediated not only by antibody formation but also by T-lymphocytes (CD4 as well as CD8 in particular), so that measurement of antibody formation is ultimately not solely informative of the expected protection against infection.

In fact, the same authors report in their recent publication a high vaccination efficacy in MS patients under DMT. Following a second vaccination, no infections were reported in all patients including those receiving high efficacy DMT.

Therefore, based on the currently available data, we recommend that vaccination should also be given under DMT. There is a reasonable prospect of achieving a sufficient vaccine response even with ongoing DMT except for conditions of total B-cell depletion. In the case of ocrelizumab, data exist on vaccination 3 months after administration of therapy, so this time window can be followed if possible. If this is not possible, vaccination against SARS-CoV-2 can be given whenever possible in terms of the risk–benefit balance. Otherwise, the recommendations of the respective national vaccination commission should be followed. There are currently insufficient data available to verify the vaccination response by measuring antibodies, and therefore this is not recommended by the manufacturers.