SAFETY OF BIVALENT SARS-COV-2 VACCINES AS A SECOND BOOSTER DOSE IN ARTHRITIS PATIENTS ON IMMUNOSUPPRESSIVE THERAPIES

BackgroundSafety and efficacy of updated bivalent vaccines, containing both the original vaccine variant of SARS-CoV-2 Spike and either Omicron variants BA.1 or BA.4/5, are of particular interest in arthritis patients on immunosuppressive therapies. With the continuous emergence of new viral variants, it is important to evaluate whether updated vaccines induce more adverse events in this patient group.ObjectivesTo examine if a second booster dose with updated bivalent vaccine increases the risk of adverse events, compared to the first booster dose with monovalent vaccines.MethodsThe prospective Nor-vaC study investigates vaccine responses in patients with immune mediated inflammatory diseases using immunosuppressive therapies (1). The present analyses included arthritis patients who received two booster doses. Patients received available vaccines according to the Norwegian vaccination program. The current recommendation in the Norwegian arthritis population is a three-dose primary vaccination series followed by two booster doses. Adverse events following vaccines doses were self-reported through questionnaires. Adverse events following the first (monovalent) and second (bivalent) booster were compared with McNemar's test.ResultsBetween 7th of July 2021 and 6th of December 2022 a total of 243 arthritis patients (127 rheumatoid arthritis, 65 psoriatic arthritis, 51 spondyloarthritis) on immunosuppressive therapies (Table 1) received a first, monovalent (BNT162b2, mRNA-1273) and a second, bivalent booster dose (BNT162b2 (WT/OMI BA.1), mRNA-1273.214, BNT162b2 (WT/OMI BA.4/BA.5)). Adverse events were recorded within 2 weeks in all patients (Figure 1). In total, 45 vs 49 (19% vs 20 %) patients reported any adverse event after a second, bivalent booster dose, compared to the first, monovalent booster, respectively. There was no significant difference in adverse events overall (p= 0.57). The most common adverse events after the second booster were pain at injection site (12 %), flu-like symptoms (9 %) and headache (6 %). No new safety signals emerged. A total of 15 (6 %) patients reported a disease flare after receiving the second, bivalent booster, compared to 21 (8 %) after the first, monovalent booster.ConclusionThere was no difference in adverse events between the monovalent, first booster, and the bivalent, second booster, indicating that bivalent vaccines are safe in this patient group.Reference[1]Syversen S.W. et al Arthritis Rheumatol 2022Table 1.Demographic characteristics and immunosuppressive medication in patients receiving a 1st monovalent and a 2nd bivalent booster dose.CharacteristicsPatients, n (%)Total243Age (years), median (IQR)61 (52-67)Female152 (63)Immunosuppressive medicationTNFi monoa75 (31)TNFi comboa+b72 (30)Methotrexate62 (26)Rituximab9 (4)IL-inhibitorsc6 (2)JAK-inhibitorsd11 (5)Othere8 (3)1st boosterBNT162b2106 (44)mRNA-1273137 (56)2nd boosterBNT162b2 (WT/OMI BA.1)65 (25)BNT162b2 (WT/OMI BA.4/BA.5)120 (47)mRNA-1273.214 (WT/OMI BA.1)58 (23)Results in n (%) unless otherwise specified.aTumor necrosis factor inhibitors: infliximab, etanercept, adalimumab, golimumab, certolizumab pegol.bCombination therapy: methotrexate, sulfasalazine, leflunomide, azathioprine.cInterleukin inhibitors: tocilizumab, secukinumab.dJanus kinase inhibitors: filgotinib, baricitinib, upadacitinib, tofacitinib.eOther: abatacept, sulfasalazine, leflunomide, azathioprine.Figure 1.Adverse events after bivalent vaccine as a 2nd booster dose compared to a monovalent vaccine as a 1st booster dose.[Figure omitted. See PDF]AcknowledgementsWe thank the patients and health-care workers who have participated in the Norwegian study of vaccine response to COVID-19. We thank the patient representatives in the study group, Kristin Isabella Kirkengen Espe and Roger Thoresen. We thank all study personnel, laboratory personnel, and other staff involved at the clinical departments involved, particularly Synnøve Aure, Margareth Sveinsson, May Britt Solem, Elisabeth Røssum-Haaland, and Kjetil Bergsmark.Disclosure of InterestsHilde Ørbo: None declared, Ingrid Jyssum: None declared, Anne Therese Tveter: None declared, Ingrid E. Christensen: None declared, Joseph Sexton: None declared, Kristin Hammersbøen Bjørlykke Speakers bureau: Janssen-Cilag, Grete B. Kro: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: AbbVie, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: AbbVie, Amgen, BMS MSD, Novartis, Pfizer, UCB, Ludvig A. Munthe Speakers bureau: Novartis, Cellgene, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi, ThermoFisher, Consultant of: AstraZeneca, Siri Mjaaland: None declared, John Torgils Vaage: None declared, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead, Kristin Kaasen Jørgensen Speakers bureau: Bristol-Myers Squibb, Roche, Sella Aarrestad Provan: None declared, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie/Abbott, Galapagos, Pfizer, UCB, Consultant of: AbbVie/Abbott, Galapagos, Pfizer, UCB.

Teamwork Before and During COVID-19: The Good, the Same, and the Ugly .

OBJECTIVES: The COVID 19 pandemic placed unprecedented strain on healthcare systems and workers, likely also impacting patient safety and outcomes. This study aimed to understand how teamwork climate changed during that pandemic and how these changes affected safety culture and workforce well-being. METHODS: This cross-sectional observational study of 50,000 healthcare workers (HCWs) in 3 large U.S. health systems used scheduled culture survey results at 2 distinct time points: before and during the first year of the COVID 19 pandemic. The SCORE survey measured 9 culture domains: teamwork climate, safety climate, leadership engagement, improvement readiness, emotional exhaustion, emotional exhaustion climate, thriving, recovery, and work-life balance. RESULTS: Response rate before and during the pandemic was 75.45% and 74.79%, respectively. Overall, HCWs reporting favorable teamwork climate declined (45.6%-43.7%, P < 0.0001). At a facility level, 35% of facilities saw teamwork climate decline, while only 4% saw an increase in teamwork climate. Facilities with decreased teamwork climate had associated decreases in every culture domain, while facilities with improved teamwork climate maintained well-being domains and saw improvements in every other culture domain. CONCLUSIONS: Healthcare worker teamwork norms worsened during the COVID-19 pandemic. Teamwork climate trend was closely associated with other safety culture metrics. Speaking up, resolving conflicts, and interdisciplinary coordination of care were especially predictive. Facilities sustaining these behaviors were able to maintain other workplace norms and workforce well-being metrics despite a global health crisis. Proactive team training may provide substantial benefit to team performance and HCW well-being during stressful times.

Increasing Bioburden of Candida auris Body Site Colonization is Associated with Environmental Contamination

Background: Environmental contamination is suspected to play a key role in transmission of Candida auris in healthcare facilities. We recently showed that environmental surfaces near C. auris-colonized patients are commonly recontaminated within hours after disinfection. Clinical factors contributing to environmental contamination are not well characterized. Methods: We conducted a multi-regional (Chicago, IL;Irvine, CA) prospective study of environmental contamination associated with C. auris colonization at six long-term care facilities (LTCF) and 1 acute-care hospital (ACH). On day of sampling, 5 participant body sites were cultured once, followed by routine daily room cleaning by facility staff, then targeted disinfection of high-touch surfaces with hydrogen peroxide wipes by research staff. Surfaces were cultured for C. auris using pre-moistened sponge-sticks and neutralizer immediately pre- and post-disinfection, and 4, 8, and 12 hours post-disinfection. We calculated the odds of surface recontamination after disinfection as a function of body site colonization with C. auris using generalized estimating equations to account for clustering among multiple surfaces within timepoints, patients, and facilities. Models included an interaction between facility type and colonization. Results: C. auris was cultured from ≥1 body site in 41 participants (12 ACH and 29 LTCF patients, 205 body sites) on day of sampling. Proportion of body sites colonized did not vary by facility type (Table). Although environmental contamination rates were similar prior to disinfection [ACH 38% (n=60 samples) vs LTCF 29%, (n=145 samples), p=0.209)], the proportion of surfaces recontaminated between 4–12 hours after disinfection was higher in ACH vs LTCF (n=574 samples) (Figure). Number of body sites colonized with C. auris was associated with higher odds of environmental recontamination [ACH: OR 2.16 (95% CI 1.63–2.88), p< 0.001;LTCF: OR 1.40 (95% CI 1.07–1.84), p=0.015;Interaction ACH vs LTCF p< 0.001].Figure.Percent of Environmental Surfaces Recontaminated with C. auris within 12 hours of Cleaning by Facility Type Conclusion: The number of body sites colonized was associated with odds of C. auris environmental contamination. Differences in environmental recontamination by facility type may be related to greater provider-patient interactions in ACH as a driving factor. Disclosures: Gabrielle M. Gussin, MS, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products;Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products;Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Raveena D. Singh, MA, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products;Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products;Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Raheeb Saavedra, AS, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products;Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products;Xttrium Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products Nicholas M. Moore, PhD, D(ABMM), Abbott Molecular: Grant/Research Support;Cepheid: Grant/Research Support Susan S. Huang, MD, MPH, Medline: Conducted studies in which hospitals and nursing homes received contributed antiseptic and/or environmental cleaning products;Molnlyke: Conducted clinical studies in which hospitals received contributed antiseptic product;Stryker: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic products;Xttri m Laboratories: Conducted clinical studies in which hospitals and nursing homes received contributed antiseptic product Mary K. Hayden, MD, Sanofi: Member, clinical adjudication panel for an investigational SARS-CoV-2 vaccine.

The Persistence of Anti-Spike Antibodies Following Two Sars-Cov-2 Vaccines in Patients with Inflammatory Bowel- and Joint Diseases on Immunosuppressive Therapy Compared to Healthy Controls - a Prospective Cohort Study

Introduction: Limited data is available regarding long-term effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy. Whether the persistence of vaccine-induced humoral immunity differs between IMID patients and the general public is currently unknown. Aims & Methods: IMID patients on immunosuppressive medication and healthy controls were enrolled in the prospective, observational Nor-vaC study. Serum samples were collected at two time points following two dose SARS-CoV-2 vaccination (first assessment within 6-48 days and second within 49-123 days). Sera were analysed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Anti-RBD <200 BAU /ml were defined as low levels. The estimated percent reduction in anti-RBD standardised to 30 days was calculated and factors associated with reduction were identified in multivariable regression models. The aims of the study were to compare the persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses between IMID patients and healthy controls, and to identify predictors of antibody decline. Result(s): A total of 1097 patients (190 Crohn's disease, 129 ulcerative colitis, 400 rheumatoid arthritis, 189 psoriatic arthritis, 189 spondyloarthritis) (median age 54 years [IQR 43-64];56% women) and 133 controls (age 45 years [35-56];83% women) provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [86-105] after second vaccine dose). Of the patients, 464 used tumor necrosis factor inhibitor (TNFi) monotherapy, 259 TNFi + metabolite inhibitor(s), 212 methotrexate monotherapy, 42 interleukin inhibitors, 34 vedolizumab, 29 rituximab, and 23 janus kinase inhibitors. Antibody levels were significantly lower in patients compared to controls at both assessments, with median anti-RBD 1468 BAU/ml [IQR 500-5062] in patients and 5514 BAU/ml [2528-9580] in controls (p<0.0001) and 298 BAU/ml [IQR 79-500] in patients and 715 BAU/ ml [28-2870] in controls (p<0.0001), at first and second assessment respectively. At the second assessment, anti-RBD antibody levels decreased below 200 BAU/ml in 452 (41%) patients and in 1 (0.8%) control (p<0.0001) (Table). The percentage change in anti-RBD levels were -86 % in patients and -77 % in controls (p<0.0001). In the multivariable regression analyses, patients had a greater decline in anti-RBD levels compared to controls beta -3.7 (95% CI -6.0, -1.4) (p<0.001). Use of TNFi in mono- or combination therapy was associated with the greatest decline compared to controls, beta -6.1 (95% CI -8.1, -4.1) and beta -6.4 (-8.4, -4.2) respectively (p<0.001). Conclusion(s): Within four months after the second vaccine dose, anti-Spike antibody levels declined considerably in both IMID patients and controls. Patients had lower antibody levels at the first assessment and a more pronounced decline compared to controls, and were consequently more likely to have low antibody levels four months after the second vaccine dose. Our results support that IMID patients lose humoral protection and need additional vaccine doses sooner than healthy individuals. (Table Presented).

Immunogenicity and Safety of a Three-Dose Sars-Cov-2 Vaccination Strategy in Patients with Immune-Mediated Inflammatory Diseases on Immunosuppressive Therapy

Introduction: Humoral vaccine responses to SARS-Cov-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID). Concerns have been raised regarding their protection against severe COVID-19 disease. Knowledge regarding efficacy and safety of repeated vaccination in this large patient group is currently lacking. Aims & Methods: The prospective observational Nor-vaC study (NCT04798625) enrolled adult patients on immunosuppressive therapy for inflammatory bowel-and joint diseases. Healthy controls were health care workers from participating hospitals. All participants received standard vaccines according to the national vaccination program with three doses in patients and two doses in controls. The third dose was offered to IMID patients >4 weeks after the second dose. Anti-Spike antibodies were assessed 2-4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2-4 weeks following three-and two-dose vaccination in patients and controls, respectively. Levels were compared across groups by Mann-Whitney U test. Factors associated with anti-Spike antibody level following the third dose were assessed by uni-and multivariable linear regression adjusted for time between vaccine and sampling. The aim of the study was to evaluate humoral immune responses and safety of repeated vaccination in IMID patients. Result(s): Overall, 1100 patients (156 ulcerative colitis, 217 Crohn's disease, 366 rheumatoid arthritis, 177 spondyloarthritis, and 184 psoriatic arthritis;median age 54 [IQR 42-64];602 women [55%]) and 303 controls (median age 43 [IQR 33-55];226 women [75 %]) were included. Immunosuppressants were tumor necrosis factor inhibitor (TNFi) monotherapy (n=461), TNFi with concomitant immunomodulator (n=254), methotrexate (n=220), vedolizumab (n=46), janus kinase inhibitors (n=33), and other (n=86). Vaccine series were Pfizer BNT162b2 (54% patients, 54% controls), Moderna mRNA-1273 (17% patients, 23% controls), or combination of vaccines (29% patients, 23% controls)). Patients received the third vaccine dose a median of 126 (IQR 105-154) days after the second dose. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/ml (2138-8732) compared to 4495 (1591-6639) in controls receiving two doses, p=0.27. In patients, anti-Spike antibody levels increased by a median of 1932 BAU/ ml (IQR 150-4978) from the second to the third dose, p<0.001. Factors associated with response were a greater interval between the second and third vaccine dose (>5 months) (p=0.03), vaccination with mRNA-1273 (p<0.001), and a combination of vaccines (p<0.001). Antibody levels had a slower decline-rate following the third vaccine dose, as compared to after the second dose, with a significant difference (p<0.001). Adverse events were reported by 488 (53%) and 464 (47%) patients after second and third dose, respectively, and by 196 (68%) controls. Disease flares were reported by 50 (5%) and 70 (7%) patients following the second and third dose. Conclusion(s): This large observational study shows that additional vaccine doses to IMID patients contributes to strong and sustained immune-responses comparable to healthy persons vaccinated twice. This study highlights the importance of repeated vaccination of IMID patients to ensure a stronger and more durable protection from severe COVID-19.

Emotional Exhaustion Among US Health Care Workers Before and During the COVID-19 Pandemic, 2019-2021.

Importance: Extraordinary strain from COVID-19 has negatively impacted health care worker (HCW) well-being. Objective: To determine whether HCW emotional exhaustion has increased during the pandemic, for which roles, and at what point. Design, Setting, and Participants: This survey study was conducted in 3 waves, with an electronic survey administered in September 2019, September 2020, and September 2021 through January 2022. Participants included hospital-based HCWs in clinical and nonclinical (eg, administrative support) roles at 76 community hospitals within 2 large health care systems in the US. Exposures: Safety, Communication, Organizational Reliability, Physician, and Employee Burnout and Engagement (SCORE) survey domains of emotional exhaustion and emotional exhaustion climate. Main Outcomes and Measures: The percentage of respondents reporting emotional exhaustion (%EE) in themselves and a climate of emotional exhaustion (%EEclim) in their colleagues. Survey items were answered on a 5-point scale from 1 (strongly disagree) to 5 (strongly agree); neutral or higher scores were counted as "percent concerning" for exhaustion. Results: Electronic surveys were returned by 37 187 (of 49 936) HCWs in 2019, 38 460 (of 45 268) in 2020, and 31 475 (of 41 224) in 2021 to 2022 for overall response rates of 74.5%, 85.0%, and 76.4%, respectively. The overall sample comprised 107 122 completed surveys. Nursing was the most frequently reported role (n = 43 918 [40.9%]). A total of 17 786 respondents (16.9%) reported less than 1 year at their facility, 59 226 (56.2%) reported 1 to 10 years, and 28 337 (26.9%) reported 11 years or more. From September 2019 to September 2021 through January 2022, overall %EE increased from 31.8% (95% CI, 30.0%-33.7%) to 40.4% (95% CI, 38.1%-42.8%), with a proportional increase in %EE of 26.9% (95% CI, 22.2%-31.8%). Physicians had a decrease in %EE from 31.8% (95% CI, 29.3%-34.5%) in 2019 to 28.3% (95% CI, 25.9%-31.0%) in 2020 but an increase during the second year of the pandemic to 37.8% (95% CI, 34.7%-41.3%). Nurses had an increase in %EE during the pandemic's first year, from 40.6% (95% CI, 38.4%-42.9%) in 2019 to 46.5% (95% CI, 44.0%-49.1%) in 2020 and increasing again during the second year of the pandemic to 49.2% (95% CI, 46.5%-51.9%). All other roles showed a similar pattern to nurses but at lower levels. Intraclass correlation coefficients revealed clustering of exhaustion within work settings across the 3 years, with coefficients of 0.15 to 0.17 for emotional exhaustion and 0.22 to 0.24 for emotional exhaustion climate, higher than the .10 coefficient typical of organizational climate (a medium effect for shared variance), suggestive of a social contagion effect of HCW exhaustion. Conclusions and Relevance: This large-scale survey study of HCWs spanning 3 years offers substantial evidence that emotional exhaustion trajectories varied by role but have increased overall and among most HCW roles since the onset of the pandemic. These results suggest that current HCW well-being resources and programs may be inadequate and even more difficult to use owing to lower workforce capacity and motivation to initiate and complete well-being interventions.

THE PERSISTENCE of ANTI-SPIKE ANTIBODIES FOLLOWING TWO SARS-COV-2 VACCINES in PATIENTS with IMMUNE-MEDIATED INFLAMMATORY DISEASES USING IMMUNOSUPPRESSIVE THERAPY, COMPARED to HEALTHY CONTROLS

Background: Limited data is available regarding long-term effectiveness of SARS-CoV-2 vaccines in patients with immune-mediated infammatory diseases (IMIDs) on immunosuppressive therapy. Whether the persistence of vaccine-induced humoral immunity against SARS-CoV-2 differs between this patient population and the general public is currently unknown. Objectives: To compare the persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses between IMID patients using immunosuppressive medication and healthy controls and identify predictors of antibody decline. Methods: We included patients with infammatory joint-and bowel diseases on immunosuppressive medication and healthy controls enrolled in the prospective observational Nor-vaC study. Serum samples were collected at two time points following two dose SARS-CoV-2 vaccination (frst assessment within 6-48 days and second within 49-123 days). Sera were analysed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Anti-RBD <200 BAU/ml were defned as low levels. The estimated percent reduction in anti-RBD standardised to 30 days was calculated and factors associated with reduction were identifed in multivariable regression models. Results: A total of 1097 patients (400 rheumatoid arthritis, 189 psoriatic arthritis, 189 spondyloarthritis, 129 ulcerative colitis, 190 Crohńs disease) (median age 54 years [IQR 43-64];56% women) and 133 controls (median age 45 years [IQR 35-56];83% women) provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [86-105] after second vaccine dose). Antibody levels were significantly lower in patients compared to controls at both assessments, with median anti-RBD 1468 BAU/ml [IQR 500-5062] in patients and 5514 BAU/ml [2528-9580] in controls (p<0.0001) and 298 BAU/ml [IQR 79-500] in patients and 715 BAU/ml [28-2870] in controls (p<0.0001), at first and second assessment respectively. Figure 1 show antibody levels at both assessments after medication group. At the second assessment, anti-RBD antibody levels decreased below 200 BAU/ml in 452 (41%) patients and in 1 (0.8%) control (p<0.0001) (Table 1). The percentage change in anti-RBD levels were-86 % in patients and-77 % in controls (p<0.0001). The majority of patients using rituximab had low antibody levels at both assessments, Figure 1. In the multivariable regression analyses, patients had a greater decline in anti-RBD levels compared to controls β-3.7 (95% CI-6.0,-1.4) (p<0.001). Use of tumor necrosis factor inhibitors in mono-or combination therapy was associated with the greatest decline compared to controls, β-6.1 (95% CI-8.1,-4.1) and β-6.4 (-8.4,-4.2) respectively (p<0.001). Conclusion: Within four months after the second vaccine dose, anti-Spike antibody levels declined considerably in both IMID patients and controls. Patients had lower antibody levels at the frst assessment and a more pronounced decline compared to controls, and were consequently more likely to have low antibody levels four months after the second vaccine dose. Our results support that IMID patients lose humoral protection and need additional vaccine doses sooner than healthy individuals.

SEROLOGICAL RESPONSE and SAFETY of A THREE-DOSE SARS-COV-2 VACCINATION STRATEGY in PATIENTS with IMMUNEMEDIATED INFLAMMATORY DISEASES on IMMUNOSUPPRESSIVE THERAPY

Background: Patients with immune-mediated infammatory diseases (IMIDs) on immunosuppressive therapy have an inadequate serologic response following two-dose SARS-CoV-2 vaccination, and a standard vaccination strategy of three doses for this patient group is currently under implementation in several countries. However, the serological response and safety of this strategy has not been evaluated. Objectives: To assess serological response and safety of a three-dose vaccination strategy in IMID patients on immunosuppressive therapy as compared to standard two-dose vaccination of healthy controls. Methods: The prospective observational Nor-vaC study (NCT04798625) enrolled adult patients on immunosuppressive therapy for infammatory joint-and bowel diseases. Healthy controls were health care workers from participating hospitals. All participants received standard vaccines according to the national vaccination program with three doses in patients and two doses in controls. The third dose was offered to IMID patients >4 weeks after the second dose. Analyses of antibodies binding the receptor-binding domain of the SARS-CoV-2 Spike protein were performed prior to, and 2-4 weeks after the second and third vaccine doses. Levels were compared across groups by Mann-Whitney U tests and multi-variate linear regression was used to identify predictors of response. Results: Overall, 961 patients (315 rheumatoid arthritis, 156 spondyloarthritis, 171 psoriatic arthritis, 132 ulcerative colitis and182 Crohn's disease) (median age 54 years [IQR 43-64];56 % women) and 227 controls (median age 44 years [IQR 32-55];83 % women) were included in the present analyses. TNFi mon-otherapy was used by 399 patients, 229 used TNFi in combination with other immunomodulators, 189 methotrexate monotherapy, 39 vedolizumab, 32 JAKi and 73 patients used other drugs. Patients on rituximab were not included. Patients were vaccinated with Pfzer BNT162b2 (54% patients, 14% controls), Moderna mRNA-1273 (16% patients, 40% controls) or a combination of vaccines (30% patients, 46% controls). Patients received the third vaccine dose a median of 120 (IQR 102-143) days after the second dose. After two doses, median antiSpike antibody levels were signifcantly lower in patients (861 BAU/ml (IQR 418-4275) than controls (6318 BAU/ml (IQR 2468-9857)), p<0.001 (Figure 1). Following the third dose, patients achieved antibody levels comparable to the two-dose vaccinated controls (median 5480 BAU/ml (IQR 1081-12069), p=0.28) (Figure 1). In the patients anti-Spike antibody levels increased by a median of 2685 BAU/ml (IQR 265-9129) from the second to the third dose. Main factors associated with increased antibody level after the third dose were younger age (β-87.7 (p=0.002)), and vaccine status (mRNA-1273 vaccine (β 5549 (p<0.001)) or a combination of vaccines (β 4367.3 (p<0.001)). Adverse events were reported by 438 (48%) of patients after the third dose as compared to 471 (54%) after the second dose and 193 (78 %) of controls. Disease fares were reported by 42 (5%) and 69 (8%) patients after the second and third dose, respectively. Conclusion: This study suggests that a third vaccine dose for immunosup-pressed patients closes the gap in serological response between patients and the healthy population. Antibody levels following the three-dose regimen in IMID patients were comparable to healthy controls vaccinated twice, and no new safety issues emerged. This fnding was consistent across all diagnoses and treatment groups, supporting the implementation of a three-dose vaccine regimen as standard in the IMID population.

IMMUNOGENICITY AND SAFETY OF STANDARD AND THIRD DOSE SARS-COV-2 VACCINATION IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES;A PROSPECTIVE COHORT STUDY

Introduction: The immunogenicity and safety following standard two-dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking. Methods & Aims: This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (<100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARSCoV- 2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies. Results: a total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40-63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32-55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls were responders, p<0,001. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192-4191]) than controls (median 3355 AU/ml [IQR 896–7849]), p<0,001. Response was shown in ≤90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80–90% of patients receiving TNFi combination therapy and secukinumab and in £ 80% for JAK inhibitors (78%), and abatacept (53%) (fig.1). Lower age (OR 0.96 [95% CI 0.95–0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4–11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported. Conclusion: Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weak-responding IMID-patients. (Figure Presented) Fig.1 Anti-SARS-CoV-2 IgG antibodies following standard two dose SARS-CoV-2 vaccination according to medication group, compared to healthy controls. Violin plot showing the probability density of the data at different values, smoothed by a kernel density estimator. Each data point is a participant, and the solid orange line show the group median. The last row (CTRL vs) shows p-values for a comparison (Mann-Whitney U test) of anti-SARS-COV 2 antibodies between medication groups and healthy controls. ACE=Angiotensin converting enzyme, FL=full length, CTRL=Controls, TNF=Tumor necrosis factor inhibitor, TNF+= Tumor necrosis factor inhibitor combination therapy, MTX=methotrexate, VDZ=vedolizumab, JAK=Janus kinase inhibitor, TCZ=tocilizumab, UST=ustekinumab, ABA=abatacept, SCK=secukinumab.

Immunogenicity and safety of standard and third dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases;a prospective cohort study

Background: The immunogenicity and safety following standard twodose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking. Methods: This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (<100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies. Results: A total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40-63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32-55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls (p<0,001) were responders. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192-4191]) than controls (median 3355 AU/ml [IQR 896-7849]), p<0,001. Response was shown in ≥90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80-90% of patients receiving TNFi combination therapy and secukinumab and in ≤ 80% for JAK inhibitors (78%), and abatacept (53%) (Fig 1). Lower age (OR 0.96 [95% CI 0.95-0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4-11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported. Conclusion: Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weakresponding IMID-patients.

"Listen to the Feedback of Students": First-Generation College Students Voice Inequalities in Schooling Brought on by the COVID-19 Pandemic

In March 2020, the higher-education community faced one of its largest disruptions to date with the COVID-19 pandemic forcing campuses to close their doors to thousands of students. The university-wide closures prompted a collaboration between researchers and college administrators to assess the impact of COVID-19 on First-Generation College Students (FGCS). The team surveyed 659 FGCS across five U.S. universities to assess the ways in which the pandemic exacerbated already existing inequalities students faced in their persistence to graduate from college. The team used the social cognitive career theory as a conceptual framework for analysis. Our findings revealed that when respondents compared their life before COVID-19 with their present state, FGCS were less likely to perceive they had enough money to return to college, felt overwhelmed and lonely by added stress, and were more likely to see an increase in family responsibilities.

A Norwegian study of immune responses to coronavirus disease 2019 (COVID-19) vaccines in patients using immunosuppressive medication within rheumatology: The Nor-vaC study

Objectives: To assess the strength and duration of the immunological response to coronavirus disease 2019 (COVID-19) vaccines in patients treated with immunosuppressive medication for inflammatory arthritis. Methods: Adult patients with a clinical diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA) or psoriatic arthritis (PsA) on treatment with any biological, conventional synthetic, or targeted synthetic disease-modifying anti-rheumatic drug (bDMARD, csDMARD, or tsDMARD) or prednisolone in doses above 7.5 mg/day are eligible for inclusion in the Nor-vaC observational study. Exclusion criteria are allergy and/or intolerance to elements of the COVID-19 vaccines. Cohorts of healthy controls have also been established, recruiting healthcare workers at Diakonhjemmet Hospital, Akershus University Hospital, and Oslo University Hospital. Serum samples are obtained from all participants before the first vaccine dose and 1-4 weeks after full vaccination. Samples are analysed for antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) using Microsphere Affinity Proteomics (MAP) (1). Demographic data and data regarding immunosuppressive medication and adverse events related to vaccination are recorded. Information regarding vaccination status, and potential COVID-19 testing and disease are obtained from relevant registers. To further elucidate the immune response to COVID-19 vaccines, we also plan to evaluate the T-cell response in a subgroup of vaccinated patients. Serum samples are planned to be collected for assessment every 3-6 months during the study period of 5 years. Results: From 15 February to 6 April 2021, 1735 patients were enrolled in the study, with at least one serum sample obtained from 892;and 130 participants have also provided samples for T-cell analyses. The distribution of diagnoses and medication is shown in Table PP25. Study recruitment, and serological and cellular analyses are currently ongoing, with the first results expected in early autumn 2021. Conclusions: Arthritis patients on long-term immunosuppressive medication may be at risk for a reduced vaccine response. Determining how robust is their immune response, and how long-lasting, will be crucial in decision making with regard to adjustments in medication and to assess a possible need for revaccination. This question is of urgent importance to Norwegian patients as well as for the global population.

The Science of Health Care Worker Burnout: Assessing and Improving Health Care Worker Well-Being.

CONTEXT.­: Problems with health care worker (HCW) well-being have become a leading concern in medicine given their severity and robust links to outcomes like medical error, mortality, and turnover. OBJECTIVE.­: To describe the state of the science regarding HCW well-being, including how it is measured, what outcomes it predicts, and what institutional and individual interventions appear to reduce it. DATA SOURCES.­: Peer review articles as well as multiple large data sets collected within our own research team are used to describe the nature of burnout, associations with institutional resources, and individual tools to improve well-being. CONCLUSIONS.­: Rates of HCW burnout are alarmingly high, placing the health and safety of patients and HCWs at risk. To help address the urgent need to help HCWs, we summarize some of the most promising early interventions, and point toward future research that uses standardized metrics to evaluate interventions (with a focus on low-cost institutional and personal interventions).