Predictors of a weak antibody response to COVID-19 mRNA vaccine in systemic lupus erythematosus.

OBJECTIVES: To characterize the antibody response to COVID-19 mRNA vaccination in patients with Systemic Lupus Erythematosus (SLE) and identify predictors of poor response. METHODS: SLE patients who are followed at the Beth Israel Deaconess Medical Center Lupus Cohort (BID-LC) were enrolled. SARS-CoV-2 IgG Spike antibody was measured in patients who received two doses of either the BNT162b2 (Pfizer-BioNTech) or the mRNA-1273 (Moderna) COVID-19 vaccine (n = 62). We defined non-responders as patients with an IgG Spike antibody titer less than two-fold (< 2) the index value of the test and responders as patients with antibody levels greater or equal to two-fold (≥ 2). A web-based survey was used to collect information regarding immunosuppressive medication use and SLE flares after vaccination. RESULTS: In our cohort of lupus patients, 76% were vaccine responders. The use of two or more immunosuppressive drugs was associated with being a non-responder (Odds Ratio 5.26; 95% CI 1.23-22.34, p = 0.02). Both Belimumab use and higher Prednisone dose were associated with vaccine non-response (p = 0.04 and p = 0.04). The non-responder group had higher mean levels of serum IL-18 than the responder group (p = 0.04) as well as lower C3 levels (p = 0.01). Lupus flares and breakthrough infections were uncommon post-vaccination. CONCLUSIONS: Immunosuppressive medications have a negative impact on vaccine humoral response in SLE individuals. We observed a trend towards vaccine no-response in BNT162b2 recipients and a relationship between IL-18 and impaired antibody response that merits further investigation.

Implementing a Virtual Flipped Classroom in a Rheumatology Fellowship Program.

OBJECTIVE: Active learning opportunities within graduate medical education may be underused. We aimed to assess whether active learning strategies increase after implementing a faculty development workshop and transitioning rheumatology fellowship didactics to a virtual flipped classroom. METHODS: We measured baseline faculty use of active learning strategies during lectures within the Introductory Rheumatology Curriculum by calculating an "active learning score" from a cognitive learning theory assessment tool. We held a faculty development workshop demonstrating active teaching strategies and encouraged using a flipped classroom for fellowship didactics. Because of the COVID-19 pandemic, the strategies were discussed in a virtual classroom setting where the intervention phase would occur. We compared active learning scores before and after the intervention for lectures within the Introductory Rheumatology Curriculum. The primary outcome was the change in active teaching scores preintervention versus postintervention. RESULTS: Active learning scores increased in 14 of the 16 lectures, with a mean score increase of 4.7 of 24 points (95% confidence interval 2.3-7.2). Paired t-test analyses comparing active learning scores preintervention and postintervention for each lecture confirmed that results were highly statistically significant (P < 0.001). Despite faculty hesitancy to teach within a virtual environment, faculty satisfaction remained high postintervention. CONCLUSION: A virtual flipped classroom increased the use of active learning strategies within the Introductory Rheumatology Curriculum. Faculty satisfaction remained high despite modest increases in time spent updating their presentations. Fellows and faculty reported a largely positive experience within the virtual classroom.

Seroconversion among rituximab-treated patients following SARS-CoV-2 vaccine supplemental dose.

Rituximab (RTX) is a very effective treatment for autoimmune rheumatic diseases (AIRD), but it increases infection risk and impairs vaccine responses. Herein we evaluated the antibody response of RTX-treated patients to the supplemental COVID-19 vaccine. After the supplemental dose, 53.1% of patients had detectable antibody titers. Only 36% of patients who did not mount an antibody response after the original vaccine series did have detectable antibodies after the supplemental dose (seroconversion). Patients with undetectable CD20+ cell levels did not seroconvert while hypogammaglobulinemia was associated with a 15-times decrease in the likelihood of seroconversion. Although we noted 11 COVID-19 infections after the supplemental dose, no patients who received monoclonal antibodies pre-exposure prophylaxis had COVID-19 afterwards. We propose that patients receiving RTX should continue to be prioritized for prophylaxis measures and that vaccination should be timed after B cell recovery wherever possible.

Immunogenicity of SARS-CoV-2 vaccination in rituximab-treated patients: Effect of timing and immunologic parameters.

Rituximab (RTX), an important therapeutic option for patients with rheumatic diseases, has been shown to reduce immune responses to various vaccines. We asked whether following SARS-CoV-2 vaccination, response rates in RTX treated patients are reduced and whether specific patient characteristics influence the responses. We recruited patients on chronic RTX therapy undergoing anti-SARS-CoV2 vaccination and measured the post-vaccination anti-spike IgG antibody levels. The median time from pre-vaccination RTX infusion to vaccination and from vaccination to the post-vaccination RTX infusion was 20.5 weeks and 7.2 weeks respectively. Only 36.5% of patients developed measurable titers of IgG anti-SARS-CoV-2 spike antibody after vaccination. Hypogammaglobulinemia (IgG and/or IgM) but not timing of vaccination, B cell numbers, or concomitant immune suppressive medications, correlated with sero-negativity (p = 0.004). Our results underscore the fact that even after B cell reconstitution, RTX induced chronic hypogammaglobulinemia significantly impairs the ability of the immune system to respond to SARS-CoV-2 vaccination.