Global Perspective on the Impact of the COVID-19 Pandemic on Rheumatology and Health Equity.

Although the public health emergency associated with the COVID-19 pandemic has ended, challenges remain, especially for individuals with rheumatic diseases. We aimed to assess the historical and ongoing effects of COVID-19 on people with rheumatic diseases and rheumatology practices globally, with specific attention to vulnerable communities and lessons learned. We reviewed literature from several countries and regions, including Africa, Australia and New Zealand, China, Europe, Latin America, and the United States. We summarize literature that not only examines the impact of the pandemic on people with rheumatic diseases, but also research that reports the lasting changes to rheumatology patient care and practice, and on health service use. Across countries, challenges faced by people with rheumatic diseases during the pandemic included disruptions in healthcare and medication supply shortages. These challenges were associated with worse disease and mental health outcomes in some studies, particularly among those who had social vulnerabilities defined by socioeconomic, race, or rurality. Moreover, rheumatology practice was impacted in all regions, with the uptake of telemedicine and changes in healthcare utilization. While many regions developed rapid guidelines to disseminate scientific information, misinformation and disinformation remained widespread. Finally, vaccine uptake among people with rheumatic diseases has been uneven across the world. As the acute phase of the pandemic wanes, ongoing efforts are needed to improve healthcare access, stabilize rheumatology drug supplies, improve public health communication, and implement evidence-based vaccination practices to reduce COVID-19 morbidity and mortality among people with rheumatic diseases.

Does the Use of Immunosuppressive Drugs Impact on SARS-CoV-2 Infection Outcome? Data From A National Cohort of Patients With Immune-Mediated Inflammatory Diseases (SAR-COVID Registry).

BACKGROUND/OBJECTIVE: This study describes the impact of immunomodulatory and/or immunosuppressive (IM/IS) drugs in the outcomes of COVID-19 infection in a cohort of patients with immune-mediated inflammatory diseases (IMIDs). METHODS: Adult patients with IMIDs with a confirmed SARS-CoV-2 infection were included. Data were reported by the treating physician between August 13, 2020 and July 31, 2021. Sociodemographic data, comorbidities, and DMARDs, as well as clinical characteristics, complications, and treatment of the SARS-CoV-2 infection, were recorded. Descriptive analysis and multivariable logistic regression models were carried out. RESULTS: A total of 1672 patients with IMIDs were included, of whom 1402 were treated with IM/IS drugs. The most frequent diseases were rheumatoid arthritis (47.7%) and systemic lupus erythematosus (18.4%). COVID-19 symptoms were present in 95.2% of the patients. A total of 461 (27.6%) patients were hospitalized, 8.2% were admitted to the intensive care unit, and 4.4% died due to COVID-19.Patients without IM/IS treatment used glucocorticoids less frequently but at higher doses, had higher levels of disease activity, were significantly older, were more frequently hospitalized, admitted to the intensive care unit, and died due to COVID-19. After adjusting for these factors, treatment with IM/IS drugs was not associated with a worse COVID-19 outcome (World Health Organization-Ordinal Scale ≥5) (odds ratio, 1.24; 95% confidence interval, 0.73-2.06). CONCLUSIONS: SAR-COVID is the first multicenter Argentine registry collecting data from patients with rheumatic diseases and SARS-CoV-2 infection. After adjusting for relevant covariates, treatment with IM/IS drugs was not associated with severe COVID-19 in patients with IMIDs. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number NCT04568421.

Risks of mortality and severe coronavirus disease 19 (COVID-19) outcomes in patients with or without systemic lupus erythematosus.

OBJECTIVES: We compared the outcomes of patients with or without systemic lupus erythematosus (SLE) who were diagnosed with coronavirus disease 19 (COVID-19) and evaluated factors within patients with SLE associated with severe outcomes. METHODS: This retrospective cohort study used the deidentified Optum COVID-19 electronic health record dataset to identify patients with COVID-19 from 1/1/2020 to 31/12/2020. Cases with SLE were matched with general controls at a ratio of 1:10 by age, sex, race and ethnicity and COVID-19 diagnosis date. Outcomes included 30-day mortality, mechanical ventilation, hospitalisation and intensive care unit admission. We evaluated the relationship between COVID-19-related outcomes and SLE using multivariable logistic regression. In addition, within SLE cases, we examined factors associated with COVID-19 related outcomes, including disease activity and SLE therapy. RESULTS: We included 687 patients matched with 6870 controls. Unadjusted rates of outcomes for patients with SLE were significantly worse than for matched controls including mortality (3.6% vs 1.8%), mechanical ventilation (6% vs 2.5%) and hospitalisation (31% vs 17.7%) (all p<0.001). After multivariable adjustment, patients with SLE had increased risks of mechanical ventilation (OR 1.81, 95% CI 1.16 to 2.82) and hospitalisation (OR 1.32, 95% CI 1.05 to 1.65). Among patients with SLE, severe disease activity was associated with increased risks of mechanical ventilation (OR 5.83, 95% CI 2.60 to 13.07) and hospitalisation (OR 3.97, 95% CI 2.37 to 6.65). Use of glucocorticoids, mycophenolate and tacrolimus before COVID-19 was associated with worse outcomes. CONCLUSION: Patients with SLE had increased risk of severe COVID-19-related outcomes compared with matched controls. Patients with severe SLE disease activity or prior use of corticosteroids experienced worse outcomes.

Association Between Race/Ethnicity and COVID-19 Outcomes in Systemic Lupus Erythematosus Patients From the United States: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population.

Cell-specific human endogenous retrovirus expression, host gene expression and SLE phenotypes

606 Figure 2Pathways of differentially expressed genes associated with high HERVs/LINEs expression per cell type in 120 SLE patients.[Figure omitted. See PDF] 606 Table 1HERVs/LINEs expression associated with clinical outcomes, adjusted for sex, race and immunosuppressive medication use in 120 SLE participants. (FDR p<0.05) HERVs/LINEs counts CD4 CD14 CD19 NK Up Down Up Down Up Down Up Down Anti Sm antibody production 5 8 5 7 21 27 2 7 Disease severity(severe 2 cluster vs mild cluster) 2 15 4 10 1087 44 461 0 History of renal disease 1 4 2 1 5 12 0 0 Anti-RNP antibody production 6 7 4 8 17 9 1 0 Anti-dsDNA antibody production 35 2 5 2 21 11 0 0 Disease activity (SLEDAI score) 1 15 2 13 2 227 0 1 Con ress, date, location Lupus 21st Century, September 20, 2022 – September 23, 2022, Loews Ventana Canyon Resort Congress website https://web.cvent.com/event/a6cd0d72-4b4e-40a4-939b- c133c05df3af/summary guidelines https://web.cvent.com/event/a6cd0d72-4b4e-40a4-939b- c133c05df3af/websitePage:795426fe-0fc9-44d7-9156-b30723c39052 Submission category • Genetics• Nucleic Acids in SLE• The Macrophage in SLE• Lupus Nephritis• Brain Injury in SLE• Pharmacoepidemiology• Clinical Research in SLE• Covid-19• Cutaneous SLE• SLE Diagnosis• Lupus-Targeted Therapeutics• Cardiovascular Disease and Lupus• PROs• Biomarkers in Clinical Trials• B Cells• Transcriptomics• T Cells• Innate Immunity• Autoantibodies• Microbiome Presentation preference N/A Character/word limit No limit stated, will ask congress to confirm Figures/tables Allowed- No limit stated, will ask congressEmbed in word doc References N/A Style Other points A lay summary is required – see separate Lay summary file Disclosures Not needed at submission Other Submission deadline August 1, 2022 at 11:59 PM ET

Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs.

Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death. RESULTS: Of 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65-1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51-0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively). CONCLUSIONS: This is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with IIM.

Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19: Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry.

OBJECTIVE: To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes. METHODS: Data on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death. RESULTS: One hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. CONCLUSION: This cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.

The impact of COVID-19 on rheumatology training-results from the COVID-19 Global Rheumatology Alliance trainee survey.

Objective: The aim was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the clinical experiences, research opportunities and well-being of rheumatology trainees. Methods: A voluntary, anonymous, Web-based survey was administered in English, Spanish or French from 19 August 2020 to 5 October 2020. Adult and paediatric rheumatology trainees were invited to participate via social media and email. Using multiple-choice questions and Likert scales, the perceptions of trainees regarding the impact of the COVID-19 pandemic on patient care and redeployment, learning and supervision, research and well-being were assessed. Results: There were 302 respondents from 33 countries, with 83% in adult rheumatology training. An increase in non-rheumatology clinical work was reported by 45%, with 68% of these having been redeployed to COVID-19. Overall, trainees reported a negative impact on their learning opportunities during rheumatology training, including outpatient clinics (79%), inpatient consultations (59%), didactic teaching (55%), procedures (53%), teaching opportunities (52%) and ultrasonography (36%). Impacts on research experiences were reported by 46% of respondents, with 39% of these reporting that COVID-19 negatively affected their ability to continue their pre-pandemic research. Burnout and increases in stress were reported by 50% and 68%, respectively. Physical health was negatively impacted by training programme changes in 25% of respondents. Conclusion: The COVID-19 pandemic has had a substantial impact on rheumatology training and trainee well-being. Our study highlights the extent of this impact on research opportunities and clinical care, which are highly relevant to future curriculum planning and the clinical learning environment.

SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry.

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2. METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

Early impacts of the COVID-19 pandemic on children with pediatric rheumatic diseases.

OBJECTIVES: The experiences of children with pediatric rheumatic diseases (PRD) during the initial phase of the COVID-19 pandemic have not been well-documented. We sought to determine the effects of the COVID-19 pandemic on protective behaviors, healthcare access, medication management, and education among an international cross-sectional parental survey of children with PRDs. METHODS: The COVID-19 Global Rheumatology Alliance Patient Experience Survey was distributed online, and parents of children with parental-reported PRD, with or without COVID-19 infection, were eligible to enroll. Respondents described their child's demographics, adoptions of protective behaviors, healthcare access, changes to immunosuppression, and disruptions in schooling. RESULTS: A total of 427 children were included in the analyses. The most common rheumatic disease was juvenile idiopathic arthritis (40.7%), and most children were taking conventional synthetic diseasemodifying antirheumatic drugs (DMARDs) (54.6%) and/or biologic DMARDs (51.8%). A diagnosis of COVID-19 was reported in five children (1.2%), none of whom required hospitalization. Seventeen children (4.0%) had stopped or delayed their drugs due to concern for immunosuppression, most commonly glucocorticoids. Almost all families adopted behaviors to protect their children from COVID-19, including quarantining, reported by 96.0% of participants. In addition, 98.3% of full-time students experienced disruptions in their education, including cancelations of classes and transitions to virtual classrooms. CONCLUSION: Despite the low numbers of children with PRDs who developed COVID-19 in this cohort, most experienced significant disruptions in their daily lives, including quarantining and interruptions in their education. The drastic changes to these children's environments on their future mental and physical health and development remain unknown.