Faculty Bibliography

Background/Purpose: Patients with systemic lupus erythematosus (SLE) are at high risk for severe disease from COVID-19 and decreased vaccine efficacy, due to inherent immune perturbations and frequent immunosuppressant use. The impact of vaccine responses was "pressure" tested in New York City (NYC) from December 2021-February 2022, due to the highly infectious omicron BA.1 variant which resulted in a significant increase in COVID-19 cases and hospitalizations. This study was performed to assess clinical efficacy and seroreactivity in SLE patients with and without an additional vaccination dose after initial vaccine series, particularly during the omicron BA.1 surge in NYC.
Method(s): COVID-19 infections after vaccination were evaluated during patient encounters and chart review in subjects from the NYU Lupus Cohort who received an initial SARS-CoV-2 vaccine series with follow-up for at least 6 months or until breakthrough infection. Clinical follow-up was required after February 4, 2022 (when NYC COVID-19 cases returned to their preomicron BA.1 baseline), with last patient follow-up recorded April 24, 2022. Positive PCR or antigen-based testing was required, performed at the clinical site or self-reported. Fifty-seven patients receiving additional vaccine doses were evaluated longitudinally for recombinant SARS-CoV-2 spike receptor binding domain antibodies (#BT10500; R&D Systems). Low post-vaccine antibody response was defined as <=100 units/ml.
Result(s): Among the 163 subjects evaluated, 125 (76.7%) received an additional COVID-19 vaccination after the initial series. Demographics and medication usage were similar in patients who did and did not receive the additional vaccination dose, with 50% on at least one immunosuppressant and 16% on more than one at the time of the initial vaccine. Twentyeight (63.6%) of the 44 patients with a breakthrough infection had received an additional vaccination compared to 97 (81.5%) of the 119 without breakthrough infection (p=0.022) (Table 1). Of the 44 COVID-19 cases, only 2 occurred prior to the omicron wave, both in patients who did not receive the additional dose. There were no COVID-19 related deaths and two patients were hospitalized. Among the 57 patients with serologic evaluation, the median antibody level after initial vaccination series was 397 u/mL (IQR 57-753), and 1036 (IQR 517-1338.5) after the additional dose. After initial vaccination, 21 (37%) had low ELISA responses, but only 4 (7%) continued to have low responses after the additional dose. There was no association between the level of antibody after the additional dose and COVID-19 breakthrough.
Conclusion(s): SLE patients from a cohort of patients in NYC who received an additional SARS-CoV-2 vaccine dose were significantly less likely to have a subsequent COVID-19 infection compared to those who only completed their initial vaccine series. SLE patients demonstrated an improvement in serologic response after an additional dose of SARS-CoV-2 vaccine. The mild disease in all vaccinated patients is reassuring given the risks inherent and frequent immunosuppressant use in this patient population

OBJECTIVE:To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multi-ethnic/racial cohort of patients with systemic lupus erythematosus (SLE). METHODS:90 SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; IFN-γ production to assess T cell responses was measured by ELISpot. Disease activity was measured by the hybrid SLE disease activity index (SLEDAI) and flares were assigned by the SELENA/SLEDAI flare index. RESULTS:Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD than controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-dsDNA level prior to vaccination associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 Spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and antigen-specific IFN-γ production determined by ELISpot. In a subset of patients with poor antibody responses, IFN-γ production was likewise diminished. Pre-/post-vaccination SLEDAI scores were similar. Only 11.4% of patients had a post-vaccination flare; 1.3% were severe. CONCLUSION/CONCLUSIONS:In a multi-ethnic/racial study of SLE patients 29% had a low response to the COVID-19 vaccine which was associated with being on immunosuppression. Reassuringly, disease flares were rare. While minimal protective levels remain unknown, these data suggest protocol development is needed to assess efficacy of booster vaccination.

Introduction Fetal cardiac disease is strongly associated with maternal anti-SSA/Ro antibodies, but gaps in our knowledge include the influence of antibody specificity and titer, maternal diagnosis, overall non-cardiac adverse pregnancy outcomes (APOs), optimal surveillance protocols, and efficacy of rapid treatment. Methods The multi-center Surveillance and Treatment To Prevent Fetal AV Block Likely to Occur Quickly (STOP BLOQ) study recruited pregnant women with commercially positive anti-Ro antibodies and stratified them into high and low titers of anti-Ro60 and Ro52 based on a research ELISA, using a cutoff defined by that obtained for 50 mothers with previous AVB offspring. Mothers with anti-Ro60 and/or 52 antibodies at or above 1,000 I.U. were trained to perform FHRM. From 17-25 weeks of gestation, FHRM was completed 3x/day in addition to weekly or biweekly fetal echocardiograms (echo). Mothers texted all audio sounds to the coordinating center. Texts deemed abnormal by mothers were immediately sent to an on call pediatric cardiologist who either reassured if FHRM was normal or referred for emergency fetal echo in < 6 hours if abnormal. Results 250 anti-Ro pregnant women (22% Hispanic, 50% white, 12% Black, 12% Asian, 4% other) have been consented, including 28 whose previous child had AVB. Of mothers tested to date, 153 were provided home monitors given high titer anti-Ro60 and/or 52 antibodies (26 high titer anti-Ro60 alone, 21 high titer anti-Ro52 alone,105 high titer antibodies to both antigens). The 83 patients with low titers were surveilled with echos per local standard of care. Regarding maternal diagnosis, of 161 assessed to date, 39% were asym/UAS, 11% RA, 31% SS, 19% SLE. Antibody titers did not significantly differ by ethnicity, race or diagnosis (table 1). Non-AVB APOs occurred in 18% and were not predicted by Ro60 or 52 titers but rather SLE diagnosis (table 2). In total, 24,759 FHRM audiotexts were received from 131 patients (90 of whom have delivered) during the monitoring period. Of these, 22 were evaluated by the on-call pediatric cardiologist, who prompted an emergency echo (all completed in < 6 hrs). In 11 cases, the emergency echo was normal. In 9, there were premature atrial contractions, confirming the mother's perception. In 2 with 2degree block on urgent echo (both treated per protocol with IVIG and dexamethasone), 1 reverted to normal sinus rhythm and the other progressed to 3degree block. In 2 others, the mother did not perceive abnormal FHRM for > 24 hrs, echo identified 3degree block, and retrospective cardiology review of FHRM audio captures identified an abnormality prior to obtaining the echo. All 4 AVB developed in fetuses of mothers with high titer antibodies to both Ro60 and 52 (mean 32,451 and 34,991 respectively). Of the 18 mothers with a previous AVB child who followed the 400mg hydroxychloroquine PATCH protocol, 1 developed AVB in accord with the results of Step 1 in that study. Conclusion These data support that APOs in this clinically diverse group of mothers are not influenced by anti-Ro titer or specificity, but rather SLE diagnosis. All conduction defects were initially identified by FHRM and in mothers with high titer anti-Ro60 and 52. Hydroxychloroquine continues to show efficacy in reducing the AVB recurrence rate with rapid intervention of emergent block being promising

Introduction: Inflammatory bowel disease (IBD), psoriasis (PsO), and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases characterized by dysregulation of the immune system. Evidence suggests that they share a common genetic and pathophysiologic pathway and that the presence of one increases the risk of developing others. While rates of PsO and PsA are increased in patients with IBD, data is lacking regarding whether phenotypic differences exist in patients with concurrent disease. In this study, we describe the disease characteristics of patients with IBD and PsO/PsA overlap.
Method(s): We performed a single-center case-control observational study. Eighty-five patients with IBD and PsO and/or PsA were identified and matched with a control group of patients with IBD alone in a 1:2 fashion based on age, sex and IBD type (n=190). Patient demographics, IBD phenotype and history, treatment patterns, and family history were collected.
Result(s): We identified 85 patients with IBD and PsO +/-PsA, matched with 190 controls. IBD 1 PsO/PsA patients were less frequently White (85% vs. 94%) and more frequently Asian (7% vs. 3%), compared with IBD only patients (P, 0.01, Table 1). There were no differences in extent of ulcerative colitis (UC) or distribution of Crohn's disease (CD), but patients with IBD alone were more likely to have penetrating Crohn's disease (48% vs. 7%; P, 0.01), prior hospitalizations (48% vs. 28%; P, 0.01), and prior surgeries (35% vs. 17%; P=0.02), compared to patients with overlap PsO +/-PsA. Rates of exposure to various biologic therapies were similar between the two groups, with the exception of decreased vedolizumab use in the IBD 1 PsO/PsA group (12% vs. 31% respectively; P, 0.01, Table 2). IBD only patients were more likely to have first-degree relatives (FDR) with IBD (35% vs. 23%; P=0.02) and numerically less likely to have a FDR with PsO or PsA (14% vs. 20%; P=0.21) than patients with PsO/PsA overlap (Table 1).
Conclusion(s): In this study, we report for the first time disease characteristics of patients with IBD and overlap PsO or PsA. Our results suggests that patients with IBD and PsO/PsA may have a less severe disease phenotype than patients with IBD alone, and that genetic risks may differ between these two groups. Further prospective studies are needed to confirm these findings

Background/Purpose: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment Methods: Patients with immune mediated inflammatory disorders (IMIDs) have an inherently heightened susceptibility to infection and may be considered high risk for developing COVID-19. While data regarding the COVID-19 vaccine's immunogenicity in an immunocompetent adult population is rapidly emerging, the ability of IMID patients to adequately respond to these vaccines is not known. Here, we investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with IMIDs on immunomodulatory treatment.
Result(s): The NY cohort baseline characteristics are found in Table 1. The Erlangen cohort consisted of 182 healthy subjects, 11 subjects with IMID receiving TNFi monotherapy, and 20 subjects with IMID on MTX monotherapy. In both cohorts, healthy individuals and those with IMID not on MTX were similar in age, while those IMID patients receiving MTX were generally older. In the NY cohort, of the healthy participants, 96.3% demonstrated adequate humoral immune response. Patients with IMID not on MTX achieved a similar rate of high antibody response rate (91.8%), while those on MTX had a lower rate of adequate humoral response (75.0%) (Figure 1A). This remains true even after the exclusion of patients who had evidence of prior COVID-19 infection (P= 0.014). Of note, 3 out of the 4 IMID patients receiving rituximab did not produce an adequate response. Similarly, in the Erlangen validation cohort, 98.3% of healthy controls, 90.9% of patients with IMID receiving TNFi monotherapy, and 50.0% receiving MTX monotherapy achieved adequate immunogenicity (Figure 1B). These differences remain significant when combining the cohorts, using a stricter definition of adequate response, and in a subgroup analysis by age. Cellular response was also analyzed in a subgroup of the NY cohort before and after second vaccination. Activated CD8+ T cells (CD8+ T cells expressing Ki67 and CD38) and the granzyme B-producing subset of these activated CD8+ T cells, were induced in immunocompetent adults and those with IMID not on MTX, but not induced in patients receiving MTX (Figure 2).
Conclusion(s): In two independent cohorts of IMID patients, MTX, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking MTX to increase the chances of immunization efficacy against SARS-CoV-2, as has been demonstrated for other viral vaccines

Background/UNASSIGNED:Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods/UNASSIGNED:For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings/UNASSIGNED:67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. Interpretation/UNASSIGNED:Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. Funding/UNASSIGNED:National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.