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.

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study.

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 µg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology.

Risk of severe COVID-19 outcomes associated with rheumatoid arthritis and phenotypic subgroups: a retrospective, comparative, multicentre cohort study.

Background: Rheumatoid arthritis has been associated with severe COVID-19, but few studies have investigated how phenotypes of rheumatoid arthritis affect these associations. We aimed to investigate the associations between rheumatoid arthritis and phenotypes of interstitial lung disease, serostatus, and bone erosions with COVID-19 severity. Methods: We did a retrospective, comparative, multicentre cohort study at two large health-care systems (Mayo Clinic [19 hospitals and affiliated outpatient centres] and Mass General Brigham [14 hospitals and affiliated outpatient centres]) in the USA. Consecutive patients with rheumatoid arthritis meeting the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria and who had COVID-19 between March 1, 2020, and June 6, 2021, were matched 1:5 on age, sex, and calendar date with patients without rheumatoid arthritis (comparators). Data were received from electronic health records from Mayo Clinic and Mass General Brigham. We examined subgroups of patients with rheumatoid arthritis by phenotypic features: rheumatoid arthritis-associated interstitial lung disease, seropositivity (for anti-cyclic citrullinated peptide, rheumatoid factor, or both), and bone erosions. Severe COVID-19 was a composite of hospitalisation or death. We used Cox regression to estimate hazard ratios (HR) for severe COVID-19, comparing rheumatoid arthritis and subgroups to the comparator group. Findings: We identified 582 patients with rheumatoid arthritis and 2875 matched comparators, all of whom had COVID-19 within the study dates. The mean age of those with rheumatoid arthritis was 62 [SD 14] years, 421 (72%) of 582 were women and 161 (28%) were men, 457 (79%) were White, 65 (11%) were Hispanic or Latino, and 41 (7%) were Black. Among patients with rheumatoid arthritis, 50 (9%) of 582 had interstitial lung disease, 388 (68%) of 568 were seropositive, and 159 (27%) of 582 had bone erosions. Severe COVID-19 occurred in 126 (22%) of 582 patients with rheumatoid arthritis versus 363 (13%) 2875 in the comparator group. Patients with rheumatoid arthritis had an HR of 1·75 (95% CI 1·45-2·10) for severe COVID-19 versus the comparator group. Patients with rheumatoid arthritis-associated interstitial lung disease had an HR of 2·50 (1·66-3·77) versus the comparator group for severe COVID-19. The risk for severe COVID-19 was also higher in patients with rheumatoid arthritis who were seropositive (HR 1·97 [95% CI 1·58-2·46]) or had erosive disease (1·93 [1·41-2·63]) than for those in the comparator group. Interpretation: Patients with rheumatoid arthritis have an increased risk of severe COVID-19 across phenotypic subgroups, especially among patients with interstitial lung disease. These findings suggest that rheumatoid arthritis with interstitial lung disease, or its treatment, might be a substantial contributor to severe COVID-19 outcomes for patients with rheumatoid arthritis. Funding: None.

Utilization of preventive services in a systemic lupus erythematosus population-based cohort: a Lupus Midwest Network (LUMEN) study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population. METHODS: All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations. RESULTS: We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85-1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58-0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13-1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96-1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11-2.87; and HR 3.19, 95% CI 2.31-4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12-1.54; and HR 2.06, 95% CI 1.38-3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81-1.69). CONCLUSIONS: The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.

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.

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.

Development of a Prediction Model for COVID-19 Acute Respiratory Distress Syndrome in Patients With Rheumatic Diseases: Results From the Global Rheumatology Alliance Registry.

OBJECTIVE: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. METHODS: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. RESULTS: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. CONCLUSION: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.

COVID-19 Vaccine Uptake Among Patients With Systemic Lupus Erythematosus in the American Midwest: The Lupus Midwest Network (LUMEN).

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at higher risk of poor outcomes from coronavirus disease 2019 (COVID-19). The vaccination rate among such patients is unknown. We aimed to assess COVID-19 vaccine uptake among patients with SLE. METHODS: We included 342 patients with SLE from the Lupus Midwest Network (LUMEN) and 350 age-, sex-, race-, and county-matched comparators. Vaccination uptake for influenza, pneumococcal, and zoster vaccines before pandemic restrictions began (up to February 29, 2020) was assessed. First-dose COVID-19 vaccine uptake was electronically retrieved and manually ascertained (December 15, 2020, to July 31, 2021). Time to COVID-19 vaccination, demographics, SLE manifestations, medications, Charlson Comorbidity Index, Area Deprivation Index, and Rural-Urban Commuting Area codes were compared. RESULTS: On July 31, 2021, 83.3% of patients with SLE and 85.5% of comparators were vaccinated against COVID-19. The COVID-19 vaccination rates were similar among SLE and comparators (hazard ratio 0.93, 95% CI 0.79-1.10). Unvaccinated patients with SLE were more likely than vaccinated patients to be men (27.3% vs 14.1%), younger (mean age 54.1 vs 58.8 yrs), have a shorter SLE duration (median 7.3 vs 10.7 yrs), and be less frequently vaccinated with influenza and pneumococcal vaccines. CONCLUSION: Patients with SLE in the Lupus Midwest Network had similar COVID-19 vaccination uptake as matched comparators, most of whom were vaccinated early when the vaccine became available. One in 6 patients with SLE remain unvaccinated.

SARS-CoV-2 Infection and COVID-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients. METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models. RESULTS: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. CONCLUSION: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Antigen Specific Humoral and Cellular Immunity Following SARS-CoV-2 Vaccination in ANCA-Associated Vasculitis Patients Receiving B-Cell Depleting Therapy.

Humoral vaccine responses are known to be suboptimal in patients receiving B-cell targeted therapy, and little is known about vaccine induced T-cell immunity in these patients. In this study, we characterized humoral and cellular antigen-specific anti-SARS-CoV2 responses following COVID-19 vaccination in patients with ANCA-associated vasculitis (AAV) receiving anti-CD20 therapy, who were either B-cell depleted, or B-cell recovered at the time of vaccination and in normal control subjects. SARS-CoV-2 anti-spike (S) and anti-nucleocapsid (NC) antibodies were measured using electrochemiluminescence immunoassays, while SARS-CoV-2 specific T-cell responses to S glycoprotein subunits 1 (S1) and 2 (S2) and receptor binding domain peptide pools were measured using interferon-gamma enzyme-linked immunosorbent spot (ELISPOT) assays. In total, 26 recently vaccinated subjects were studied. Despite the lack of a measurable humoral immune response, B-cell depleted patients mounted a similar vaccine induced antigen-specific T-cell response compared to B-cell recovered patients and normal controls. Our data indicate that to assure a humoral response in patients receiving anti-CD20 therapy, SARS-CoV-2 vaccination should ideally be delayed until B-cell recovery (CD-20 positive B-cells > 10/µl). Nevertheless, SARS-CoV-2 vaccination elicits robust, potentially protective cellular immune responses in these subjects. Further research to characterize the durability and protective effect of vaccine-induced anti-SARS-CoV-2 specific T-cell immunity are needed.

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study.

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1ß, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

The protective effect of rheumatic disease agents in COVID-19.

Several immunosuppressive therapies have been investigated as potential treatments for patients with severe and critical coronavirus disease 2019 (COVID-19). Notable examples include corticosteroids, interleukin 6 (IL-6), interleukin 1 (IL-1), Janus kinase (JAK), and tumor necrosis factor alpha (TNF-α) inhibitors. The aim of this narrative review is to analyze the mechanistic rationale and available evidence for these selected anti-rheumatic drugs for the treatment of COVID-19. Currently, only corticosteroids have consistently proven to be effective in decreasing mortality and are recommended in clinical guidelines for the treatment of severe and critical COVID-19. Multiple randomized controlled trials (RCTs) are ongoing to determine the role of other immunosuppressants.