Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis: data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data.

OBJECTIVES: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). METHODS: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. RESULTS: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor. CONCLUSIONS: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Telemedicine in the Management of Patients with Rheumatic Disease during COVID-19 Pandemic: Incidence of Psychiatric Disorders and Fibromyalgia in Patients with Rheumatoid Arthritis and Psoriatic Arthritis.

The management of patients with immuno-rheumatological diseases has profoundly changed during the COVID-19 pandemic and telemedicine has played an important role in the disease follow-up. In addition to monitoring disease activity and any adverse events, especially infectious events, assessing the psychological situation of the patient can be fundamental. Furthermore, COVID-19 has a serious impact on mental health and, since the beginning of the pandemic, a significantly higher incidence of anxiety disorders and depressive symptoms especially in younger people was observed. In this study, we evaluated the incidence of depressive disorders, anxiety, and fibromyalgia (FM) in our patients with rheumatoid arthritis and psoriatic arthritis during the lockdown period due to the COVID-19 pandemic and we validate the use of telemedicine in the clinical management of these patients. Mental and physical stress during the COVID-19 pandemic can greatly worsen FM symptoms and intensify patients' suffering without a clinical flare of the inflammatory disease for patients affected by rheumatoid arthritis. Telemedicine has allowed us to identify patients who needed a face-to-face approach for therapeutic reevaluation even if not related to a flare of the inflammatory disease. Even if our data does not allow us to draw definitive conclusions regarding the effectiveness of telemedicine as greater than or equal to the standard face-to-face approach, we continue to work by modifying our approach to try to ensure the necessary care in compliance with safety and, optimistically, this tool will become an important part of rheumatic disease management.

Assessing the Risk and Outcome of COVID-19 in Patients with Psoriasis or Psoriatic Arthritis on Biologic Treatment: A Critical Appraisal of the Quality of the Published Evidence.

The need to rapidly spread information about the risk of COVID-19 in patients with psoriasis and psoriatic arthritis on biologics may have hampered the methodological rigor in published literature. We analyzed the quality of papers dealing with the risk and outcomes of COVID-19 in patients with psoriasis and psoriatic arthritis receiving biologic therapies. The Newcastle-Ottawa Scale was used to estimate the quality of the published studies. Moreover, to better contextualize results, specific internal and external validity items were further considered, that is, case definition, modality of COVID-19 assessment, evidence for self-selection of participants, percentage of dropout/nonparticipants, and sample size calculation. A total of 25 of 141 papers were selected. The median Newcastle-Ottawa Scale score was 47% for psoriasis and 44% for psoriatic arthritis, indicating an overall high risk of bias. A total of 37% of psoriasis and 44% of psoriatic arthritis studies included patients with suspected COVID-19 without a positive swab. No studies provided a formal sample size calculation. A significant risk of bias in all the published papers was found. Major issues to be considered in future studies are reduction of ascertainment bias, better consideration of nonresponse or participation bias, and provision of formal statistical power calculation.

SARS-CoV-2 Infection Induces Psoriatic Arthritis Flares and Enthesis Resident Plasmacytoid Dendritic Cell Type-1 Interferon Inhibition by JAK Antagonism Offer Novel Spondyloarthritis Pathogenesis Insights.

Objective: Bacterial and viral infectious triggers are linked to spondyloarthritis (SpA) including psoriatic arthritis (PsA) development, likely via dendritic cell activation. We investigated spinal entheseal plasmacytoid dendritic cells (pDCs) toll-like receptor (TLR)-7 and 9 activation and therapeutic modulation, including JAK inhibition. We also investigated if COVID-19 infection, a potent TLR-7 stimulator triggered PsA flares. Methods: Normal entheseal pDCs were characterized and stimulated with imiquimod and CpG oligodeoxynucleotides (ODN) to evaluate TNF and IFNα production. NanoString gene expression assay of total pDCs RNA was performed pre- and post- ODN stimulation. Pharmacological inhibition of induced IFNα protein was performed with Tofacitinib and PDE4 inhibition. The impact of SARS-CoV2 viral infection on PsA flares was evaluated. Results: CD45+HLA-DR+CD123+CD303+CD11c- entheseal pDCs were more numerous than blood pDCs (1.9 ± 0.8% vs 0.2 ± 0.07% of CD45+ cells, p=0.008) and showed inducible IFNα and TNF protein following ODN/imiquimod stimulation and were the sole entheseal IFNα producers. NanoString data identified 11 significantly upregulated differentially expressed genes (DEGs) including TNF in stimulated pDCs. Canonical pathway analysis revealed activation of dendritic cell maturation, NF-κB signaling, toll-like receptor signaling and JAK/STAT signaling pathways following ODN stimulation. Both tofacitinib and PDE4i strongly attenuated ODN induced IFNα. DAPSA scores elevations occurred in 18 PsA cases with SARS-CoV2 infection (9.7 ± 4 pre-infection and 35.3 ± 7.5 during infection). Conclusion: Entheseal pDCs link microbes to TNF/IFNα production. SARS-CoV-2 infection is associated with PsA Flares and JAK inhibition suppressed activated entheseal plasmacytoid dendritic Type-1 interferon responses as pointers towards a novel mechanism of PsA and SpA-related arthropathy.

COVID-19 in Patients With Inflammatory Arthritis: A Prospective Study on the Effects of Comorbidities and Disease-Modifying Antirheumatic Drugs on Clinical Outcomes.

OBJECTIVE: To characterize the hospitalization and death rates among patients with inflammatory arthritis (IA) affected by coronavirus disease 2019 (COVID-19) and to analyze the associations of comorbidities and immunomodulatory medications with infection outcomes. METHODS: Data on clinical and demographic features, maintenance treatment, disease course, and outcomes in individuals with IA (rheumatoid arthritis and spondyloarthritis) with symptomatic COVID-19 infection were prospectively assessed via web-based questionnaire followed by individual phone calls and electronic medical record review. Baseline characteristics and medication use were summarized for hospitalized and ambulatory patients, and outcomes with the different medication classes were compared using multivariable logistic regression. RESULTS: A total of 103 patients with IA were included in the study (80 with confirmed COVID-19 and 23 with high suspicion of COVID-19). Hospitalization was required in 26% of the participants, and 4% died. Patients who were hospitalized were significantly more likely to be older (P < 0.001) and have comorbid hypertension (P = 0.001) and chronic obstructive pulmonary disease (P = 0.02). IA patients taking oral glucocorticoids had an increased likelihood of being admitted for COVID-19 (P < 0.001), while those receiving maintenance anticytokine biologic therapies did not. CONCLUSION: Among patients with underlying IA, COVID-19 outcomes were worse in those receiving glucocorticoids but not in patients receiving maintenance anticytokine therapy. Further work is needed to understand whether immunomodulatory therapies affect COVID-19 incidence.

National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD.

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. METHODS: Using an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. RESULTS: Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. CONCLUSIONS: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.

Coronavirus disease 2019 (COVID-19) in autoimmune and inflammatory conditions: clinical characteristics of poor outcomes.

OBJECTIVE: To describe clinical characteristics of patients with rheumatic and musculoskeletal diseases (RMDs) and immunosuppressive therapies with Coronavirus disease 2019 (COVID-19) at an academic rheumatology center in Madrid and to identify baseline variables associated with a severe infection requiring hospitalization. METHODS: We identified SARS-CoV-2 positive cases by polymerase chain reaction performed at our center within an updated RMDs database in our clinic. Additional RMDs patients were identified when they contacted the clinic because of a positive infection. Data extraction included diagnosis, demographics, immunosuppressive treatment, comorbidities, and laboratory tests. Comparisons between patients with or without hospitalization were performed. Multivariate logistic regression was used to analyze associations between baseline variables and need for hospitalization. RESULTS: A total of 62 patients with COVID-19 and underlying RMDs were identified by April 24, 2020. Median age was 60.9 years, and 42% men. Forty-two patients required hospitalization; these were more frequently men, older and with comorbidities. There were no statistically significant between-group differences for rheumatologic diagnosis and for baseline use of immunosuppressive therapy except for glucocorticoids that were more frequent in hospitalized patients. Total deaths were 10 (16%) patients. In multivariate analysis, male sex (odds ratio [OR], 8.63; p = 0.018), previous lung disease (OR, 27.47; p = 0.042), and glucocorticoids use (> 5 mg/day) (OR, 9.95; p = 0.019) were significantly associated to hospitalization. CONCLUSION: Neither specific RMD diagnoses or exposures to DMARDs were associated with increased odds of hospitalization. Being male, previous lung disease and exposure to glucocorticoids were associated with higher odds of hospitalization in RMDs patients.

Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study.

OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.

Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. METHODS: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. RESULTS: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. CONCLUSIONS: We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.