COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series.

OBJECTIVE: To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease. METHODS: We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed. RESULTS: Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2-53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection. CONCLUSION: In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.

Immunogenicity and safety of high-dose versus standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: a randomised, double-blind, active-comparator trial.

BACKGROUND: Patients with rheumatoid arthritis have increased risk of seasonal influenza and influenza-related complications but have reduced vaccine immunogenicity. It is unknown whether patients with rheumatoid arthritis would benefit from more immunogenic vaccine formulations. This study investigated the immunogenicity and safety of a high-dose trivalent inactivated influenza vaccine (HD-TIV) in patients with rheumatoid arthritis compared to a standard-dose quadrivalent influenza vaccine (SD-QIV). METHODS: This study was a treatment-stratified, randomised, double-blind trial to compare the immunogenicity and safety of SD-QIV (15 µg of haemagglutinin [HA] per strain) versus HD-TIV (60 µg of HA per strain) in adults with rheumatoid arthritis who are positive for rheumatoid factor or anti-cyclic citrullinated peptide, or both, recruited during the 2016-17 and 2017-18 influenza seasons at three hospitals affiliated with McGill University (Montreal, QC, Canada). Participants had received treatment for rheumatoid arthritis with conventional or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) or biological DMARDs, or combinations of them, were still on treatment at the time of enrolment, and their treatment had not been modified during the 3 months before enrolment. They were stratified into one of three groups according to treatment. Patients who, at enrolment, were taking conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination were stratified to group 1; those who were taking a biological DMARD (anti-tumour necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 2; and those who were taking abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine (or a combination thereof) were stratified to group 3. Participants were randomly allocated (1:1) to receive the SD-QIV or HD-TIV vaccine. Randomisation was based on a computer-generated allocation sequence, and participants, investigators, and research nurses responsible for safety assessments were masked to vaccine assignment. The primary outcome was the seroconversion rate (as measured by haemagglutination-inhibition assay) per strain at day 28. Analysis was done in the modified intention-to-treat population, which included all randomly assigned participants for whom seroconversion status was available. Safety was assessed throughout the surveillance period (day 0-186). This trial is registered at ClinicalTrials.gov, number NCT02936180. FINDINGS: Between Oct 24, 2016, and Dec 6, 2017, 696 patients with rheumatoid arthritis were invited to participate in the study and 279 were randomly assigned and vaccinated (140 [50%] received SD-QIV and 139 [50%] HD-TIV). 136 patients who received SD-QIV and 138 who received HD-TIV were included in the modified intention-to-treat anaysis. Patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2·99 (95% CI 1·46-6·11) for seroconversion to strain A/H3N2, 1·95 (1·19-3·22) for seroconversion to strain B/Bris, 3·21 (1·57-6·56) for seroconversion to strain A/H1N1 (in 2016-2017), and 2·44 (1·18-5·06) for seroconversion to strain A/H1N1 (in 2017-2018). Similar results were observed in patients from groups 1 and 2; the number of individuals in group 3 was insufficient to draw conclusions. Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported between days 0 and 28 in any group, and neither vaccine increased rheumatoid arthritis disease activity. INTERPRETATION: Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV. These results are the first evidence to support the use of the HD-TIV in these patients. FUNDING: The Arthritis Society-Canada.

Efecto de los procesos de congelación y descongelación sobre los almidones en un alimento a base de maíz / Effect of the freezing and thawing processes on starches in a corn-based food

RESUMEN Se decidió estudiar el efecto que la cocción y el congelamiento sucesivos tiene sobre contenido de almidones y el índice glicémico (IG) de un alimento a base de harina de maíz (bollo). Se elaboró el alimento y se sometió congelamiento y cocción un par de veces. El contenido de almidones se comparó con el de la harina de maíz pre-cocida y se encontraron diferencias significativas (F = 5,84; p = 0,005), con un incremento importante del contenido de almidón resistente debido a los tratamientos térmicos. Se elaboraron curvas de glicemia a una muestra de individuos sanos, a los que se dio a consumir el alimento sometido a los diferentes tratamientos y pan integral. Se encontraron diferencias significativas (F= 4,21; p= 0,034) y un IG de 67,9 para el bollo sometido a tres procesos de cocción y dos congelamientos. Indicativo de que los procesos térmicos provocaron la aparición de una proporción de almidón retrogradado equivalente a fibra dietética que puede ser beneficioso para el organismo.

ABSTRACT We studied the effect that subsequent cooking and freezing has on the starch content and the glycemic index (GI) of a corn flour-based food (bun). The food was made and exposed to cooking and freezing a couple of times. The starch content was compared with that of precooked corn flour and significant differences were found (F = 5.84; p = 0.005), with an important increase in the retrograded starch content due to thermic treatments. Glycemic response curves were conducted for a sample of healthy individuals, who consumed the food submitted to the treatments and wholegrain bread. Significant differences were found (F = 4.21; p= 0.034) and a GI of 67.9 for the bun submitted to three cooking and two freezing processes. Results suggest that the thermic treatments induced the appearance of a retrograded starch proportion equivalent to dietary fiber which could be beneficial for the body.