#MSCOVID19: T-cell response on ocrelizumab

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Barts-MS rose-tinted-odometer: ★★★★★

As you know the vast majority of pwMS on anti-CD20 therapy who get COVID-19 or for that matter any other viral infection recover. In other words, their immune systems work despite blunted or absent B-cell or antibody responses. This study presented yesterday at the AAN meeting confirms that ocrelizumab-treated patients who get COVID-19 have good robust T-cell responses. Almost all of these patients also had antibody responses to the virus. The ocrelizumab-treated cases that fail to seroconvert may therefore represent a publication bias. However, as this study doesn’t include the 5% of subjects on ocrelizumab who succumb to COVID-19 we can’t assume this applies to all ocrelizumabers.

It will be interesting to see these results replicated with the COVID-19 vaccines. Although wild-type infection with SARS-CoV-2 is likely to provide a more robust immunological challenge than a COVID-19 vaccine, I can’t see why the vaccine won’t induce T-cell responses as well. The question will be how few patients fail to respond to the vaccine at both an antibody and T-cell level.

I am sure a large number of ocrelizumabers or anti-CD20ers and their HCPs will be relieved to see these results (or not).

Kister et al. Preliminary Results of Ongoing, Prospective Study of Antibody and T-Cell Responses to SARS-CoV-2 in Patients With MS on Ocrelizumab or Other Disease-Modifying Therapies. AAN 2021

Objective: 1. To assess SARS-CoV-2 seropositivity in 1,000 patients with multiple sclerosis (MS) and its association with demographic and disease-related characteristics, and disease-modifying therapy (DMT); 2. To evaluate the persistence of antibody and T-cell responses in a subset of these patients who were receiving ocrelizumab (OCR), other DMT or no DMT at the time of COVID-19 infection. Background: Since March 2020, ˜15% of patients attending NYU MS Care Center (NYUMSCC) in New York City had COVID-19. It is unknown whether DMTs affect the persistence of antibody and T-cell responses to SARS-CoV-2. 

Design/Methods: Patients from NYUMSCC were invited to undergo serologic assessment using Elecsys Anti-SARS-CoV-2 (Roche Diagnostics) and multiplex bead-based immunoassays of antibody responses to SARS-CoV-2 nucleocapsid and spike proteins. A subset of patients with or without COVID-19 history underwent a study of T-cell responses to SARS-CoV-2 spike protein using IFN-? enzyme-linked immunosorbent spot (Invitrogen) and TruCulture (Myriad RBM) spike protein assays and live virus immunofluorescence-based microneutralization assay. 

Results: Since January 2021, 100 unvaccinated patients with MS were enrolled (mean 41 years; 63% female; 45% non-white; 35% on OCR; 26% had COVID-19). Antibody and T-cell results were available for 40 patients (26 on OCR; 17 had COVID-19, median 10 months before sampling). Of the 40, Elecsys Anti- SARS-CoV-2 assay identified all but 2 COVID-19+ patients, and multiplex bead-based assay identified all but 1 COVID-19+ patient as seropositive. Neither assay had false positives. T-cell activation based on induced IFN-gamma secretion was observed in 10/17 COVID-19+ patients and 1 patient without COVID-19 history who developed PCR-confirmed COVID-19 five days after sampling. Anti-SARS-CoV-2 antibody response was detected in 4/5 and T-cell response in 3/5 OCR-treated COVID-19+ patients. 

Conclusions: Preliminary results suggest persistent humoral and T-cell immune memory to SARS-CoV-2 up to 10 months following infection even in B-cell depleted patients with MS. Updated results will be presented.

Conflicts of Interest

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Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

14 comments

  • This “ ocrelizumabers” is so very relieved. Thank you for the post & for articulating in such a way patients that are not HCPs nor Clinc-speak gurus can relate/understand.

  • This “ ocrelizumabers” is so very relieved. Thank you for the post & for articulating in such a way patients that are not HCPs nor Clinc-speak gurus can relate/understand!

  • Absolutely wonderful news. Though from what I’ve gathered, rituximab-treated patients suffer slightly worse outcomes in covid-19. Correct? And if so, would you expect that patients on rituximab for some reason make less effective immune-responses to covid-19 than ocrelizumab treated patients?

      • Not sure i understand. You would expect rituximab-treated patients to have less effective responses to covid-19?

      • Not sure i understand. You think rituximab-treated patients will show a less effective response to covid-19? To the vaccines aswell, then?

  • Would be nice to see if patients with Hypogammaglobulinemia and X-linked agammaglobulinemia

    Have the same outcome

  • Amazing news!! Thanks for sharing it, Prof. G.! Fingers crossed for the confirmation of these results with regard to Covid19-vaccines!

  • “Almost all of these patients also had antibody responses to the virus. The ocrelizumab-treated cases that fail to seroconvert may therefore represent a publication bias.” These two sentences kind of scare though, or are not clear to me… Do they mean that those who don’t seroconvert would also not develop the T-cell response? I mean: what about those Ocrelizumabers who have been infected by Covid-19 but did not sieroconvert? And what about Covid19 vaccines, which, according to the preliminary data from Israel that this blog reported a few weeks ago, don’t trigger a detectable antibody response in 80% of the Ocrelizumabers? Should we still be worried or it is legitimate to assume that T-cell response is also triggered in patients – either covid-19 infected or vaccinated – that don’t seroconvert? Thanks

  • I had my first Pfizer jab 10 weeks after OCR infusion and the second a month later. I took the vaccine when it was offered to me since I have young kids that recently resumed in person school. I just received a positive spike antibody test (after a negative nucleocapsid test because the lab ran the wrong antibody test). In the past, I’ve had no CD20 repopulation at 6 months, so should I be surprised by this? Much of the conversation has focused on timing the vaccines correctly.

    • Well done glad you realised that nucelocapsid is useless assay for most vaccines and all currently available in UK, rest of Europe and US. Looking at data there are some people that have produced antibodies when vaccinated less than 5 months from infusion. At 3 months this not unheard of. Just because you cant see B cells in the blood does not mean that they are not in lymph glanads and bone marrow.

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