The rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in the coronavirus disease 2019 (COVID-19) pandemic. To contain this pandemic, scientists have developed several vaccines, and many of those have received emergency use authorization (EUA) from global regulatory bodies. Subsequently, vaccination programs have commenced in many countries.

Study: A cohort of 222 anti-CD20 treated patients with multiple sclerosis followed through the COVID-19 pandemic: Attenuated humoral but robust cellular immune responses after vaccination and infection. Image Credit: ADragan/ Shutterstock

Multiple sclerosis patients and COVID-19 vaccination

The effect of newly developed COVID-19 vaccines on patients with varied underlying illnesses is not known. It is imperative to understand the effect of vaccines on immunosuppressed patients and individuals undergoing immunotherapies. For multiple sclerosis patients (pwMS), management of immunotherapies and COVID-19 vaccination plays an important role in protecting them from the lethal disease. Management of immune therapies is important because B-cell depleting anti-CD20 therapies have been linked with an increased possibility of severe SARS-CoV-2 infection and decreased humoral immune responses to vaccinations.

Previous studies have reported a reduced level of SARS-CoV-2 immunoglobulin (IgG) after natural infection of vaccination in pwMS receiving anti-CD20 treatment. Additionally, protection from SARS-CoV-2 also depends on the neutralizing capacity and avidity of anti-SARS-CoV-2 antibodies and the production of SARS-CoV-2 specific T cells. Researchers have pointed out that very limited studies on the neutralization capacity of SARS-CoV-2 antibodies in anti-CD20 treated pwMS.

A new study

A new study published on the medRxiv* preprint server has focused on the immune response in pwMS undergoing anti-CD20 treatment. To evaluate SARS-CoV-2 specific humoral immune responses in anti-CD20 treated pwMS, researchers obtained sera samples from the MS referral center, Charité – Universitätsmedizin Berlin, Germany, between March 2020 and August 2021.

In this study, researchers reported the results from the analyses of humoral and cellular immune responses following SARS-CoV-2 vaccination or immune responses induced after natural COVID-19 infections in a single-center cohort. The cohort comprised 222 pwMS, out of which 128 were female. The median age was 39 years, and 181 patients were on anti-CD20 therapy at inclusion. The remaining began therapy during the study. The patients were followed through the first seventeen months of the COVID-19 pandemic. Hospital employees served as control, and there were 19 of them.

Main findings

Scientists performed a comprehensive analysis of SARS-CoV-2 specific humoral and cellular immune responses and observed that the antibody responses (levels and functionality) were reduced in anti-CD20 treated pwMS. It was also observed that the patients with MS undergoing anti-CD20 therapy developed robust T cell responses post-SARS-CoV-2 vaccinations/infections.

Further, the rate of detecting SARS-CoV-2 infections in anti-CD20-treated pwMS was not significantly different from that of the general population. Researchers presented the last result with the caveat that it was not possible to be certain that the rate of SARS-CoV-2 infections in anti-CD20 treated pwMS was underestimated. This was since infections were mainly detected based on antibodies, which may be undetectable under anti-CD20 therapy.

It was observed that the SARS-CoV-2 antibody levels, avidity, and neutralizing capacity were augmented as more time passed between the anti-CD20 therapy and the administration of the second SARS-CoV-2 vaccine dose. This suggests that vaccines should be administered as late as possible to enhance humoral immune responses within the six-month infusion cycles of intravenous anti-CD20 therapy. Also, since antibody responses in anti-CD20 treated pwMS are reduced over time, additional booster vaccination doses should be considered for this group of individuals.

Limitations of the study

One major limitation of this study involved the lack of data on total lymphocyte and B cell counts during SARS-CoV-2 vaccinations/infections. Therefore, these parameters, as potential risk factors for low vaccine immunogenicity, could not be analyzed. Secondly, the follow-up time was quite short, and more work is needed to evaluate the anti-SARS-CoV-2 antibodies, and T cell responses in anti-CD20 treated patients over longer time horizons. This is particularly important, given that immune responses wane over time. Finally, the majority of pwMS were vaccinated with the BNT162b2 vaccine. This prevented the comparison of immunogenicity across different vaccines.

Conclusion

Scientists conducted an observational study to show that the levels and functionality of anti-SARS-CoV-2 antibodies are diminished in vaccinated or infected anti-CD20 treated pwMS. However, the T cell responses are preserved, hinting that these patients develop at least some degree of protection from COVID-19. One way of enhancing the level and functionality of SARS-CoV-2 antibody responses could be to allow a longer interval between anti-CD20 infusions and vaccination. It was also observed that the rate of SARS-CoV2 infections in pwMS was not significantly different from the general population. These findings could guide treatment and management decisions of SARS-CoV-2 vaccinations in pwMS.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.