Some Patients on Rituximab Fail to Mount Robust T-cell Response to COVID-19 Vaccine

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by Vanda Pinto PhD |

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Note: This story was updated Feb. 22, 2022, to update the headline and clarify that some patients on rituximab do not mount an effective T-cell response to the COVID-19 vaccine.

A significant proportion of patients on rituximab, including those with ANCA-associated vasculitis, fail to mount effective antibody and T-cell responses to the Pfizer-BioNTech vaccine, putting them at greater risk of severe COVID-19 outcomes, a study has found.

While it was known that most people taking rituximab do not mount a robust antibody response when they get vaccinated for COVID-19, the study shows that over 40% also fail to develop T-cell responses after three vaccine doses.

Moreover, being 65 or older and having a low number of total T-cells are significant predictors of a poor T-cell response after three doses of the vaccine.

The study, “T-cell response to 3 doses of Sars-Cov2 BNT162b2 Pfizer vaccine in long term rituximab treated patients,” was published as a letter to the editor in the European Journal of Internal Medicine.

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Rituximab for AAV Linked to Poor Responses to COVID-19 Vaccines

Rituximab, commercially available as Rituxan, among other brand names, is an antibody treatment used for a number of autoimmune diseases and some forms of cancer. The therapy targets and eliminates immune B-cells, which are involved in antibody production and responsible for the self-reacting antibodies that cause autoimmune diseases such as AAV and other autoimmune conditions.

However, treatments that lower B-cell numbers are associated with an increased risk of severe COVID-19 disease and often preclude patients from mounting adequate immune responses to the vaccines.

In these patients, other parts of the immune system such as T-cells might still respond to the vaccines — and, therefore, confer protection against COVID-19. Yet, very few studies have evaluated T-cell responses to SARS-CoV-2, the virus that causes COVID-19, after vaccination.

A team of scientists at Dijon University Hospital in France set out to determine whether people treated with rituximab had preserved T-cell responses against SARS-CoV-2 after receiving three doses of the Pfizer vaccine.

These responses were assessed by measuring the levels of interferon gamma — a chemical messenger widely produced by activated T-cells — in cells exposed to SARS-CoV-2 proteins. Essentially, if patients had T-cells that could specifically recognize these viral proteins, these cells would become activated, and produce large amounts of interferon gamma.

The researchers also determined antibody responses by quantifying the levels of SARS-CoV-2 antibodies.

The study included 28 patients who received rituximab at the university hospital and three doses of the Pfizer vaccine, after which a blood sample was collected (the time from vaccination to sample collection was not disclosed in the study).

The majority of patients (13) had AAV; other diseases included IgG4-related disease, immune thrombocytopenia (shortage of blood cells called platelets needed for clotting), anti-MAG neuropathy, systemic sclerosis, rheumatoid arthritis, chronic polyradiculoneuropathy, and Waldenström macroglobulinemia (type of non-Hodgkin’s lymphoma).

At the time of the analysis, patients had a median disease duration of six years, and had received a median of six rituximab infusions (range of 4–13). The last dose of rituximab had been taken less than six months prior to the analysis.

Results showed that 57% of patients had a preserved T-cell response to the vaccines, while the remaining did not. Responders were significantly younger (median age 56.5 years vs. 71 years), had a higher number of lymphocytes (immune cells that include B-cells and T-cells), and more often had recovered to normal B-cell numbers.

Ten out of the 28 patients developed antibodies against SARS-CoV-2. Consistent with more responders having normal B-cell numbers, the levels of SARS-CoV-2 antibodies tended to be higher in patients with a T-cell response.

“It is of concern that some rituximab-treated patients do not develop a humoral [antibody] or T cell response after vaccination and should therefore be prioritized to receive prophylactic cocktails of neutralizing antibodies, especially during epidemic periods,” the researchers wrote.

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3rd COVID-19 Vaccine Seen to ‘Strongly’ Raise Patients’ Immunity

No differences were observed between responders and non-responders in other factors, including disease duration, number of infusions, time elapsed since the last rituximab infusion, and previous or current treatments.

Statistical analysis then showed being 65 or older and having a low level of T-cells (less than 1 million cells per mL) were both associated with a significantly greater likelihood of having a poor T-cell response.

“Our data show that most rituximab-treated patients have a poor humoral response to [SARS-CoV-2] after complete vaccination with 3 doses of [the] Pfizer vaccine and surprisingly, some have an additional T-cell immune response defect, suggesting that the risk of a severe form is further increased in these patients,” the investigators wrote.

“Consideration of age and circulating T cell count may predict a poor T-cell immune response after [SARS-CoV-2] vaccination,” they concluded.