| Cross-sectional case-control studies  

Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy

People living with multiple sclerosis (MS) and other disorders treated with immunomodulatory therapies remain concerned about suboptimal responses to coronavirus disease 2019 (COVID-19) vaccines. Important questions persist regarding immunological response to third vaccines, particularly with respect to newer virus variants. The objective of this observational study was to evaluate humoral and cellular immune responses to a third COVID-19 vaccine dose in people on anti-CD20 therapy and sphingosine 1-phosphate receptor (S1PR) modulators, including Omicron-specific assays.

The immunological responses to third COVID-19 vaccine dose in participants treated with anti-CD20 agents, S1PR modulators, and healthy controls was evaluated. Neutralizing antibodies against USA-WA1/2020 (WA1) and B.1.1.529 (BA.1) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were measured before and after third vaccine. Groups were compared by one-way ANOVA with Tukey multiple comparisons. Cellular responses to spike peptide pools generated from WA1 and BA.1 were evaluated. Pre-post comparisons were made by Wilcoxon paired t-tests, inter-cohort comparisons by Mann-Whitney t-test. This cohort includes 25 participants on anti-CD20 therapy, 12 on S1PR modulators, and 14 healthy controls. Among those on anti-CD20 therapy, neutralizing antibodies to WA1 were significantly reduced compared to healthy controls (ID50% GM post-vaccination of 8.1 ± 2.8 in anti-CD20 therapy group vs 452.6 ± 8.442 healthy controls, P < 0.0001) and neutralizing antibodies to BA.1 were below the threshold of detection nearly universally. However, cellular responses, including to Omicron-specific peptides, were not significantly different from controls. Among those on S1PR modulators, neutralizing antibodies to WA1 were detected in a minority, and only 3/12 had neutralizing antibodies just at the limit of detection to BA.1. Cellular responses to Spike antigen in those on S1PR modulators were reduced by a factor of 100 compared to controls (median 0.0008% vs. 0.08%, p < 0.001) and were not significantly "boosted" by a third injection. The authors concluded that participants on anti-CD20 and S1PR modulator therapies had impaired antibody neutralization capacity, particularly to BA.1, even after a third vaccine. T cell responses were not affected by anti-CD20 therapies but were nearly abrogated by S1PR modulators.

Katz Sand I, Gnjatic S, Krammer F, Tuballes K, Carreño JM, Satyanarayan S, Filomena S, Staker E, Tcheou J, Miller A, Fabian M, Safi N, Nichols J, Patel J, Krieger S, Tankou S, Horng S, Klineova S, Beck E, Merad M, Lublin F. Evaluation of immunological responses to third COVID-19 vaccine among people treated with sphingosine receptor-1 modulators and anti-CD20 therapy. Mult Scler Relat Disord. 2022 Dec 28;70:104486.

doi: 10.1016/j.msard.2022.104486