BackgroundImmune responses on 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.MethodsWe searched PubMed, Embase, Medrxiv and SSRN using variations of search terms ‘anti-CD20’, ‘vaccine’ and ‘COVID’ and included original studies up to 21 August 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 COVID-19 or incomplete vaccine courses. Primary endpoints were humoral and cell-mediated immune response rates. Subgroup analyses included time since anti-CD20 therapy, B cell depletion and indication for anti-CD20 therapy. We used random-effects models of proportions.FindingsNinety studies were assessed. Inclusion criteria were met by 23 studies comprising 1342 patients. Overall rate of humoral response was 0.40 (95% CI 0.35 to 0.47). Overall rate of cell-mediated immune responses was 0.71 (95% CI 0.57 to 0.87). A time interval >6 months since last anti-CD20 therapy was associated with higher humoral response rates with 0.63 (95% CI 0.53 to 0.72) versus <6 months 0.2 (95% CI 0.03 to 0.43); p=0<01. Similarly, patients with circulating B cells more frequently showed humoral responses. Anti-CD20-treated kidney transplant recipients showed lower humoral response rates than patients with haematological malignancies or autoimmune disease.InterpretationPatients 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 therapy and depleted B cell are at high risk for non-seroconversion and should be individually assessed for personalised SARS-CoV-2 vaccination strategies. Potential limitations are small patient numbers and heterogeneity of studies included.FundingThis study was funded by Bern University Hospital.

Background Findings on the effects of vitamin D on cognitive performance have been inconsistent and no clinical trials with detailed cognitive testing in healthy older adults have been reported. Objectives We tested whether 2000 IU is superior to 800 IU vitamin D3/d for cognitive performance among relatively healthy older adults. Design We analyzed data on cognitive performance as the secondary outcome of a 2-y double-blind randomized controlled trial that originally investigated the effect of vitamin D3 on knee function and pain in seniors with osteoarthritis. Participants were randomly assigned to either 2000 or 800 IU vitamin D3/d. Capsules had identical appearances and taste. A total of 273 community-dwelling older adults aged ≥60 y were enrolled 6–8 wk after unilateral joint replacement. Inclusion required a baseline Mini Mental State Examination (MMSE) score of 24. We implemented a detailed 2-h cognitive test battery. The primary cognitive endpoint was the score achieved in the MMSE. Secondary endpoints included a composite score of 7 executive function tests, auditory verbal and visual design learning tests, and reaction times. Results At baseline, mean age was 70.3 y, 31.4% were vitamin D–deficient [25(OH)D <20 ng/mL], and mean ± SD MMSE score was 28.0 ± 1.5. Although the mean ± SD 25(OH)D concentrations achieved differed significantly between treatment groups at 24-mo follow-up (2000 IU = 45.1 ± 10.2 ng/mL; 800 IU = 37.5 ± 8.8 ng/mL; P < 0.0001), none of the primary or secondary endpoints of cognitive performance differed between treatment group. Results by treatment were similar for predefined subgroups of baseline 25(OH)D status (deficient compared with replete) and age (60–69 y compared with ≥70 y). Conclusions Our study does not support a superior cognitive benefit of 2000 IU compared with 800 IU vitamin D/d among relatively healthy older adults over a 24-mo treatment period. This trial was registered at clinicaltrials.gov as NCT00599807.

Based on the present case report and user web-reports, as well as on the chemical structure and pharmacological characteristics, naphyrone produces stimulant-like psychotropic effects and sympathomimetic toxicity.

ObjectiveTo test whether daily high-dose vitamin D improves recovery after unilateral total knee replacement.MethodsData come from a 24-month randomised, double-blind clinical trial. Adults aged 60 and older undergoing unilateral joint replacement due to severe knee osteoarthritis were 6–8 weeks after surgery randomly assigned to receive daily high-dose (2000 IU) or standard-dose (800 IU) vitamin D3. The primary endpoints were symptoms (Western Ontario and McMaster Universities Arthritis Index pain and function scores) assessed at baseline, 6, 12, 18 and 24 months in both knees, and the rate of falls over 24 months. The secondary outcomes were sit-to-stand performance, gait speed, physical activity and radiographic progression in the contralateral knee.ResultsWe recruited 273 participants, 137 were randomised to receive 2000 IU and 136 were randomised to receive 800 IU vitamin D per day. 2000 IU vitamin D increased 25-hydroxyvitamin D levels to 45.6 ng/mL and 800 IU vitamin D to 37.1 ng/mL at month 24 (p<0.0001). While symptoms improved significantly in the operated knee and remained stable in the contralateral knee over time, none of the primary or secondary endpoints differed by treatment group over time. The rate of falls over 24 months was 1.05 with 2000 IU and 1.07 with 800 IU (p=0.84). 30.5% of participants in the 2000 IU and 31.3% of participants in the 800 IU group had radiographic progression in the contralateral knee over 24 months (p=0.88).ConclusionsOur findings suggest that a 24-month treatment with daily 2000 IU vitamin D did not show greater benefits or harm than a daily standard dose of 800 IU among older adults undergoing unilateral total knee replacement.

BackgroundThe majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients.MethodsWe investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6–4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression.Results5.6 months (IQR: 5.1–6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0–7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants.ConclusionThis study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.