SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study

B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.

Author list

Adrian M Shields,  Srinivasan Venkatachalam,  Salim Shafeek,  Shankara Paneesha, Mark Ford,  Tom Sheeran,  Melanie Kelly,  Iman Qureshi,  Beena Salhan,  Farheen Karim, Neelakshi De Silva,  Jacqueline Stones,  Sophie Lee,  Jahanzeb Khawaja, Praveen Kumar Kaudlay,  Richard Whitmill,  Ghulam Nabi Kakepoto,  Helen M Parry, Paul Moss,  Sian E Faustini,  Alex G Richter,  Mark T Drayson,  Supratik Basu

Novel Coronavirus SARS-CoV-2


Clinical & Experimental Immunology