IntroductionVaccination represents a cornerstone in mastering the COVID-19 pandemic. Data on immunogenicity and safety of messenger RNA (mRNA) vaccines in patients with autoimmune inflammatory rheumatic diseases (AIIRD) are limited.MethodsA multicentre observational study evaluated the immunogenicity and safety of the two-dose regimen BNT162b2 mRNA vaccine in adult patients with AIIRD (n=686) compared with the general population (n=121). Serum IgG antibody levels against SARS-CoV-2 spike S1/S2 proteins were measured 2–6 weeks after the second vaccine dose. Seropositivity was defined as IgG ≥15 binding antibody units (BAU)/mL. Vaccination efficacy, safety, and disease activity were assessed within 6 weeks after the second vaccine dose.ResultsFollowing vaccination, the seropositivity rate and S1/S2 IgG levels were significantly lower among patients with AIIRD versus controls (86% (n=590) vs 100%, p<0.0001 and 132.9±91.7 vs 218.6±82.06 BAU/mL, p<0.0001, respectively). Risk factors for reduced immunogenicity included older age and treatment with glucocorticoids, rituximab, mycophenolate mofetil (MMF), and abatacept. Rituximab was the main cause of a seronegative response (39% seropositivity). There were no postvaccination symptomatic cases of COVID-19 among patients with AIIRD and one mild case in the control group. Major adverse events in patients with AIIRD included death (n=2) several weeks after the second vaccine dose, non-disseminated herpes zoster (n=6), uveitis (n=2), and pericarditis (n=1). Postvaccination disease activity remained stable in the majority of patients.ConclusionmRNA BNTb262 vaccine was immunogenic in the majority of patients with AIIRD, with an acceptable safety profile. Treatment with glucocorticoids, rituximab, MMF, and abatacept was associated with a significantly reduced BNT162b2-induced immunogenicity.

BackgroundKetamine has been demonstrated to improve depressive symptoms.AimsEvaluation of efficacy, safety and feasibility of repeated oral ketamine for out-patients with treatment-resistant depression (TRD).MethodIn a randomised, double-blind, placebo-controlled, proof-of-concept trial, 41 participants received either 1 mg/kg oral ketamine or placebo thrice weekly for 21 days (ClinicalTrials.gov Identifier: NCT02037503). Evaluation was performed at baseline, 40 and 240 min post administration and on days 3, 7, 14 and 21. The main outcome measure was change in Montgomery–Åsberg Depression Rating Scale (MADRS).ResultsTwenty-two participants were randomised to the ketamine group, and 19 to the control, with 82.5% (n = 33) completing the study. In the ketamine group, a decrease in depressive symptoms was evident at all time points, whereas in the control group a decrease was evident only 40 min post administration. The reduction in MADRS score on day 21 was 12.75 in the ketamine group versus 2.49 points with placebo (P < 0.001). Six participants in the ketamine group (27.3%) achieved remission compared with none of the controls (P < 0.05). The number needed to treat for remission was 3.7. Side-effects were mild and transient.ConclusionsRepeated oral ketamine produced rapid and persistent amelioration of depressive symptoms in out-patients with TRD, and was well tolerated. These results suggest that add-on oral ketamine may hold significant promise in the care of patients suffering from TRD in the community.Declaration of interestNone.

Objective Data regarding the neurodevelopmental outcome of fetal short corpus callosum (CC) diagnosed according to standard reference charts is scarce. The purpose of this study was to assess whether the finding is related to neurodevelopmental delay, and to examine reclassification to normal fetal CC length using CC length/EFW ratio. Method Historical prospective cohort study including pregnant women who were referred for fetal neurosonogram due to abnormal CC. Short CC was defined below the 5th percentile according to reference charts. Twenty cases were included in the study group and compared with a control group of 59 normal cases. The patients in the study group were divided into two groups according to CC length/EFW ratio. Children's neurodevelopment was assessed using the Vineland Adaptive Behavior Scale (VABS). Results VABS scores were within normal range in 90% of the cases. There was no significant statistical difference between the study group and the control group. In addition, there was no statistically significant difference between fetuses reclassified as normal callosal length according to CC length/EFW ratio in comparison to the control group. Conclusion The neurodevelopmental outcome of fetuses with diagnosed short CC did not differ from the neurodevelopment of normal fetuses in the control group.

Development of autoantibodies following BNT162b2 mRNA COVID-19 vaccination and their association with disease flares in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and the general population: results of 1-year prospective follow-up study. We conducted a prospective study aimed at investigating the incidence of appearance of autoantibodies (antinuclear, antiphospholipid, and rheumatoid factor) in the sera of 463 adult patients with AIIRD compared to 55 controls from the general population prior to, and following the second and third vaccine doses, and at 1-year of follow-up. Pre- and post-vaccination disease activity indices and the association of autoantibodies with rheumatic disease flares and new onset AIIRD were examined. Autoantibody development of any type in AIIRD patients vs. the controls was 4.0% (vs. 6.7%, p = 0.423) following two vaccine doses and 7.6% (vs. 0%, p = 0.152) after three doses. There was no significant difference in sex, age, or disease-type among individuals with and without autoantibody development, regardless of the immunosuppressant use. More patients developed autoantibodies following the third than the second vaccine dose (p = 0.004). Disease flares occurred in 5.8% and 7.2% of AIIRD patients following second and third vaccine doses, respectively, with autoantibody production increasing the risk of flares following the second (p = 0.002) and third (p = 0.004) vaccine doses. BNT162b2 vaccination resulted in the development of autoantibodies in a minority of AIIRD patients and controls. Autoantibody development was associated with disease flares in patients, but no new-onset autoimmunity was observed.

No abstract

Marked fatigue is common in patients with systemic lupus erythematosus (SLE). This study aimed to assess the association of sleep disorders, including obstructive sleep apnea (OSA), with SLE. Forty-two consecutive patients with SLE and 20 healthy controls were recruited and underwent a one-night ambulatory sleep examination. They completed questionnaires, including the Pittsburgh Sleep Quality Index (PSQI) and Functional Assessment of Chronic Illness Therapy (FACIT). SLE disease activity and damage were assessed by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). A significantly increased apnea/hypopnea index was noted in the SLE group compared to healthy controls (p = 0.004). SLE patients had higher rates of moderate-to-severe OSA (p = 0.04), PSQI (p = 0.001), and FACIT scores (p = 0.0008). Multivariate analysis revealed that the SDI was associated with OSA (p = 0.03). There was a positive association between SLEDAI-2K and moderate-to-severe OSA (p = 0.03). Patients with SLE had an increased prevalence of OSA and poorer quality of sleep compared to healthy controls. Our findings suggest that active disease and accumulated damage may be associated with OSA. These findings highlight the importance of identifying the presence of OSA in patients with SLE.

No abstract

No abstract