This is a pre-copyedited, author-produced version of an article accepted for publication in Rheumaology following peer review. The version of record [insert complete citation information here] is available online at: xxxxxxx [insert URL and DOI of the article on the OUP website].

B cell depleting agents are amongst 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 (<1m) 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 (>36m 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.

Consecutive general practitioner referrals to three general medical clinics were examined prospectively to assess whether the reason for referral was being correctly interpreted by consultants. The resultant data revealed that although this was not always the case, such misunderstandings did not appear to affect subsequent management. Explicit reasons for referral in the referral letter however could improve both the quality and value of out-patient consultations.

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DesCripTionAn 83-year-old man presented with an acute history of weight loss and jaundice. He had a history of type 2 diabetes mellitus and hypertension. He consumed 30 units of alcohol per week.The patient was cachectic and jaundiced with non-tender hepatomegaly and no evidence of chronic liver disease. There was evidence of hypoalbuminaemia (albumin 25 g/L, reference 34-51 g/L), hyperbilirubinaemia (bilirubin 188 μmol/L, reference <22 μmol/L) and a raised alkaline phosphatase (629 IU/L, reference 35-105 IU/L). Full blood count, coagulation tests and the remaining liver function tests were normal. An estimated Glomerular filtration rate (eGFR) was 71 mL/ min/1.73 m 2 . Autoantibodies and immunoglobulins were normal. Hepatitis viral serology was negative. Serum light chain measurements revealed kappa chain concentration of 13.3 (reference 3.3-19.4 mg/L) and lambda chain concentration of 28.5 (reference 5.7-26.6 mg/L) with a ratio of 0.47 (reference 0.26-1.75). A CT abdomen revealed hepatomegaly and ascites.

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