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Immune response to SARS-CoV-2 infection and vaccination in patients with multiple sclerosis

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The rapid spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused a pandemic of Coronavirus Disease 2019 (COVID-19). To contain this pandemic, scientists have developed several vaccines, many of which have received Emergency Use Authorization (EUA) from global regulators. Since then, vaccination programs have been launched in many countries.

study: A cohort of 222 patients treated with anti-CD20 for multiple sclerosis following a COVID-19 pandemic: humoral but strong cell-mediated immune response attenuation after vaccination and infection.. Image Credit: ADragan / Shutterstock

Multiple sclerosis patients and COVID-19 vaccination

The impact of the newly developed COVID-19 vaccine on patients with a variety of underlying diseases is unknown. It is essential to understand the effects of vaccines on immunosuppressed patients and individuals receiving immunotherapy. For patients with multiple sclerosis (pwMS), immunotherapy and management of COVID-19 vaccination play an important role in protecting patients from fatal illness. Management of immunotherapy is important because B-cell depletion anti-CD20 therapy is associated with an increased likelihood of severe SARS-CoV-2 infection and a reduced humoral immune response to vaccination.

Previous studies have reported reduced levels of SARS-CoV-2 immunoglobulin (IgG) after spontaneous vaccination with pwMS receiving anti-CD20 treatment. In addition, protection from SARS-CoV-2 depends on the neutralizing and binding capacity of anti-SARS-CoV-2 antibodies, as well as SARS-CoV-2 specific production. T cells.. Researchers have pointed to very limited research on the ability of SARS-CoV-2 antibodies to neutralize anti-CD20-treated pwMS.

New research

New research published in medRxiv* The preprint server focuses on the immune response of pwMS receiving anti-CD20 treatment. To evaluate the SARS-CoV-2 specific humoral immune response in anti-CD20 treated pwMS, researchers conducted serum samples from the MS Referral Center in Berlin, Charite University, Germany, between March 2020 and August 2021. I got.

In this study, researchers reported analysis of humoral and cell-mediated immune responses after SARS-CoV-2 vaccination or immune responses elicited after spontaneous COVID-19 infection in a single-center cohort. .. The cohort consisted of 222pwMS, of which 128 were women. The median age was 39 years and 181 patients received anti-CD20 therapy at enrollment. The rest started treatment during the study. Patients were followed for the first 17 months of the COVID-19 pandemic. Hospital employees were in control and there were 19 people.

Main results

Scientists performed a comprehensive analysis of SARS-CoV-2-specific humoral and cell-mediated immune responses and observed that antibody responses (levels and function) were reduced by anti-CD20-treated pwMS. Patients with MS receiving anti-CD20 therapy were also observed to develop a strong T cell response after SARS-CoV-2 vaccination / infection.

Moreover, the detection rate of SARS-CoV-2 infection in pwMS treated with anti-CD20 was not significantly different from that of the general population. The researchers presented the final results with a warning that it is not possible to confirm that SARS-CoV-2 infection rates in pwMS treated with anti-CD20 are underestimated. This is because the infection was detected primarily on the basis of antibodies and may not be detected by anti-CD20 therapy.

Over time between anti-CD20 therapy and the second SARS-CoV-2 vaccine administration, SARS-CoV-2 antibody levels, binding strength, and neutralizing capacity were observed to increase. This suggests that the vaccine should be given as late as possible to enhance the humoral immune response within the 6-month infusion cycle of intravenous anti-CD20 therapy. In addition, the antibody response of pwMS treated with anti-CD20 declines over time, so additional booster vaccination doses should be considered for individuals in this group.

Research limits

One major limitation of this study was related to the lack of data on total lymphocyte and B cell counts during SARS-CoV-2 vaccination / infection. Therefore, these parameters could not be analyzed as potential risk factors for the low immunogenicity of the vaccine. Second, the follow-up period is very short and more work is needed to assess the T cell response of patients treated with anti-SARS-CoV-2 antibody and anti-CD20 over a longer period of time. This is especially important given that the immune response declines over time. Finally, the majority of pwMS was vaccinated with the BNT162b2 vaccine. This prevented the comparison of immunogenicity between different vaccines.

Conclusion

Scientists conducted observational studies showing that vaccinated or infected anti-CD20-treated pwMS reduced the levels and function of anti-SARS-CoV-2 antibodies. However, T cell responses are retained, suggesting that these patients have developed at least some protection from COVID-19. One way to enhance the level and function of the SARS-CoV-2 antibody response is to increase the interval between anti-CD20 injection and vaccination. It was also observed that the rate of SARS-CoV2 infection in pwMS was not significantly different from that of the general population. These findings may guide treatment and management decisions for SARS-CoV-2 vaccination in pwMS.

*Important Notices

medRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.

Journal reference:

  • Schwarz, T. et al. (2021) A cohort of 222 patients treated with anti-CD20 for multiple sclerosis following the COVID-19 pandemic: humoral but strong cell-mediated immune response attenuation after vaccination and infection. medRxiv. Doi: https://doi.org/10.1101/2021.10.11.21264694

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