The global pandemic caused by COVID-19 - or more specifically, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - has led to widespread efforts to understand the immune responses in different populations, including those with underlying health conditions. One of these demographics, patients with multiple sclerosis treated with anti-CD20 therapy, demonstrate significant challenges because of their impaired immune responses. The following study, conducted by the Tisch Multiple Sclerosis Research Center of New York, examines the immune responses of anti-CD20 therapy patients after exposure to COVID-19 and finds the importance of both cellular and humoral immunity when providing protection against infection.
Anti-CD20 therapy (or aCD20-1) has been proven to be effective in the initial prevention of multiple sclerosis, but then leads to severe depletion of B cells, and an impaired ability to create viral antigen-specific immunoglobulins. The lack of B cells poses a vital risk for M.S. patients treated with aCD20-1 when they are confronted with COVID-19, needing numerous vaccine doses and booster updates to strengthen their immunity. Although humoral responses have been widely researched, the role of T-cell mediated immunity against COVID-19 gives way for priority to asses these immunocompromised populations.
This prospective study involved 203 aCD20-MS patients and 43 (healthy) controls. Immunity of patients was assessed after initial exposure to COVID-19 spike antigen and subsequent re-challenges. The investigation was heavily concentrated on evaluating both cellular and humoral immune responses, analyzing parameters such as seroconversion rates, RBD-hACE2 blocking activity, and reactions of T-cells. The T-cell responses were analyzed by measuring the secretion of essential cytokines such as IFNγ and IL-2.
Seroconversion and RBD-hACE2 inhibitory activity remained low in aCD20-MS patients even after multiple viral doses. Responders increased from 17.5% following the first intervention period to 29.3% after the second, contrasting the healthier controls who exhibited a stronger humoral response. When examining cellular immunity, healthy controls displayed a crucial increase in spike-specific T-cells following exposure. But aCD20-MS patients consistently demonstrated higher T-cell responses before and after re-exposure, underscoring their strong T-cell responses. To add, responses against BA.2, a variant of omicron, were comparable in both groups, suggesting sustained T-cell responses.
This study reveals the delicate interactions between cellular and humoral immunity within aCD20-MS patients after COVID-19 exposure. Despite the limited humoral response, these patients presented potent T-cell response, crucial for defense against infection. This highlights the value of harnessing T-cell-mediated immunity alongside humoral responses. Furthermore, personal assessments for M.S. patients using B-cell depletion therapy are vital, considering that individual immune profiles vary with protection. These insights provide important strategies for protecting immunocompromised individuals and sculpt the future of vaccine development.
Alfonso-Dunn, Roberto, et al. “Humoral and Cellular Responses to Repeated Covid-19 Exposure in Multiple Sclerosis Patients Receiving B-Cell Depleting Therapies: A Single-Center, One-Year, Prospective Study.” Frontiers, Frontiers, 6 June 2023, www.frontiersin.org/articles/10.3389/fimmu.2023.1194671/full.
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