#MSCOVID19. More from the UK and beyond

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This is the Cambridge data. They looked at the first dose and 66% did not deplete very well on CD20-depleting antibody. This is often seen with the first dose which induces a low level response. Therefore the second shot is important. After the second they got some response in about 50% of the non responders giving us about 33% failers to convert. They measured whole Spike and receptor binding domain (usually less response than with Spike),

B-cell count strongly predicted seroconversion, so if you have B cells you convert. However it can happen with not peripheral blood B cells. Although they report that time interval between dose and antibody response was not significant. With a cut off at around 6 months you would be twice as likely to sero convert. So highly consistent with what has gone before it. Likewise a poor response whether you were on Pfizer or Astrazenca vaccine

The differences in red are not significantly different (Chi-squared test) you would need four times the numbers to show a significant difference with ese proportions

Diminished seroconversion following a single SARS-COV-2 vaccine in ocrelizumab-treated relapsing-remitting multiple sclerosis patients Zoya G GeorgievaRainer DӧffingerDinakantha KumararatneAlasdair J ColesClaire McCarthy Mult Scler https://doi.org/10.1177/13524585211046786

Background: Despite impressive efficacy in immunocompetent individuals, the immunogenicity of a single dose of COVID-19 vaccine in B-cell-deplete patients remains unknown.

Methods:We measured post-vaccination SARS-COV-2 immunoglobulin G (IgG) in ocrelizumab recipients using a highly sensitive Luminex assay.

Results:44.1% of patients had detectable SARS-COV-2-IgG 21+ days after one vaccine dose, regardless of vaccine type (AZD1222 vs BNT162b2, odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.157–2.32, p = 0.72). B-cell count strongly predicted seroconversion (β1 = 12.38, 95% CI = 4.59–20.16, p = 0.0029), but undetectable B-cells did not preclude it. The second vaccine seroconverted 53% of the patients who had not already responded to dose 1.

Conclusion:Humoral response after one COVID-19 vaccine dose is lower than expected in CD20-deplete patients.

Humoral and cellular immune responses upon SARS-CoV-2 vaccines in patients with anti-CD20 therapies: A systematic review and meta-analysis of 1342 patientsSchietzel, S., Anderegg, M., Limacher, A., Born, A., Horn, M., Maurer, B., Hirzel, C., Sidler, D., Moor, M. B.10.1101/2021.09.30.21264335 — Posted: 2021-10-01

Background Immune responses upon SARS-CoV-2 vaccination in patients receiving anti-CD20 therapies are impaired but vary considerably. We conducted a systematic review and meta-analysis of the literature on SARS-CoV-2 vaccine induced humoral and cell-mediated immune response in patients previously treated with anti-CD20 antibodies.

Methods We searched PubMed, EMBASE, Medrxiv and SSRN using variations of search terms “anti-CD20”, “vaccine” and “COVID” and included original studies up to August 21st,2021. We excluded studies with missing data on humoral or cell-mediated immune response, unspecified methodology of response testing, unspecified timeframes between vaccination and blood sampling or low number of participants (≤ 3). We excluded individual patients with prior SARS-CoV-2 infection or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Pre-specified subgroups were time of vaccination after anti-CD20 therapy (< vs > 6 months), time point of response testing after vaccination (< vs > 4 weeks) and disease entity (autoimmune vs cancer vs renal transplant). We used random-effects models of proportions.

Findings Ninety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients.

  • Overall rate of humoral response was 0.41 (95% CI 0.35 – 0.47).
  • Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.47 – 0.90).
  • Longer time interval since last anti-CD20 therapy was associated with higher humoral response rates > 6 months 0.63 (95% CI 0.53 – 0.72) vs < 6 months 0.2 (95% CI 0.03 – 0.43); p = 0.001.

<6 less than 6 months >more than 6 months further to left less likely to make an antibody response more to right more likely to make an antibody response

Compared to patients with haematological malignancies or autoimmune diseases, anti-CD20 treated kidney transplant recipients showed the lowest vaccination response rates.

Interpretation Patients on anti-CD20 therapies can develop humoral and cell-mediated immune responses after SARS-CoV-2 vaccination, but subgroups such as kidney transplant recipients or those with very recent B-cell depleting therapy are at high risk for non-seroconversion and should be individually assessed for personalized SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers, heterogeneous diseases and assays used.

So there is an antibody response in only about 40% of people treated with anti-CD20 but about 70% of people make a T cell response. If you do not delay your infusions there is a 20% chance of producing an antibody response compared to 63% if you delay past 6 months. This data is however skewed because most of the non-MS data is due to rituximab use, whereas ocrelizumab use occurs in MS. This is a more potent depleter than rituximab.

It think this is pretty, pretty clear

General Disclaimer: Please note that the opinions expressed here are those of the author and do not necessarily reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust and are not meant to be interpreted as personal clinical advice.

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