OBJECTIVE: Patients living with systemic autoimmune rheumatic diseases (SARDs) continue to be concerned about risks of severe COVID-19 outcomes. METHODS: Using a large multi-center electronic health record network, we conducted a comparative cohort study of patients with SARDs diagnosed with COVID-19 (identified by diagnostic code or positive molecular test) versus non-SARD comparators with COVID-19, matched by age, sex, race/ethnicity, and body mass index (primary model) and comorbidities and health care utilization (extended model). Thirty-day outcomes were assessed, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation, acute renal failure requiring renal replacement therapy (ARF), ischemic stroke, venous thromboembolism (VTE), and death. RESULTS: We initially identified 2,379 SARD patients with COVID-19 (mean age 58 years, 79% female) and 142,750 comparators (mean age 47 years, 54% female). In the primary matched model (2,379 SARD patients and 2,379 matched non-SARD comparators with COVID-19), SARD patients had significantly higher risks of hospitalization (RR 1.14, 95% CI: 1.03 to 1.26), ICU admission (RR 1.32, 95% CI: 1.03 to 1.68), ARF (RR 1.81, 95% CI: 1.07 to 3.07), and VTE (RR 1.74, 95% CI: 1.23 to 2.45) versus comparators but did not have significantly higher risks of mechanical ventilation or death. In the extended model, all risks were largely attenuated except risk of VTE (RR 1.60, 95% CI: 1.14 to 2.25). CONCLUSIONS: SARD patients with COVID-19 may be at higher risk of hospitalization, ICU admission, ARF, and VTE versus matched comparators. These risks may be largely mediated by comorbidities, except for risk of VTE.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.41619

COVID-19 Outcomes in Patients With Systemic Autoimmune Rheumatic Diseases Compared to the General Population: A US Multicenter, Comparative Cohort Study.

Summary Background In the ongoing COVID-19 pandemic, the susceptibility of patients with rheumatic diseases to COVID-19 remains unclear. We aimed to investigate susceptibility to COVID-19 in patients with autoimmune rheumatic diseases during the ongoing COVID-19 pandemic. Methods We did a multicentre retrospective study of patients with autoimmune rheumatic diseases in Hubei province, the epicentre of the COVID-19 outbreak in China. Patients with rheumatic diseases were contacted through an automated telephone-based survey to investigate their susceptibility to COVID-19. Data about COVID-19 exposure or diagnosis were collected. Families with a documented history of COVID-19 exposure, as defined by having at least one family member diagnosed with COVID-19, were followed up by medical professionals to obtain detailed information, including sex, age, smoking history, past medical history, use of medications, and information related to COVID-19. Findings Between March 20 and March 30, 2020, 6228 patients with autoimmune rheumatic diseases were included in the study. The overall rate of COVID-19 in patients with an autoimmune rheumatic disease in our study population was 0·43% (27 of 6228 patients). We identified 42 families in which COVID-19 was diagnosed between Dec 20, 2019, and March 20, 2020, in either patients with a rheumatic disease or in a family member residing at the same physical address during the outbreak. Within these 42 families, COVID-19 was diagnosed in 27 (63%) of 43 patients with a rheumatic disease and in 28 (34%) of 83 of their family members with no rheumatic disease (adjusted odds ratio [OR] 2·68 [95% CI 1·14–6·27]; p=0·023). Patients with rheumatic disease who were taking hydroxychloroquine had a lower risk of COVID-19 infection than patients taking other disease-modifying anti-rheumatic drugs (OR 0·09 [95% CI 0·01–0·94]; p=0·044). Additionally, the risk of COVID-19 was increased with age (adjusted OR 1·04 [95%CI 1·01–1·06]; p=0·0081). Interpretation Patients with autoimmune rheumatic disease might be more susceptible to COVID-19 infection than the general population. Funding National Natural Science Foundation of China and the Tongji Hospital Clinical Research Flagship Program.

COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study.

BackgroundThe risk of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection and clinical outcomes of coronavirus disease (COVID-19) in inflammatory bowel disease are unclea...

https://onlinelibrary.wiley.com/doi/pdf/10.1177/2050640620972602

Risk and outcomes of coronavirus disease in patients with inflammatory bowel disease: A systematic review and meta-analysis.

Objectives To estimate the incidence of COVID-19 hospitalisation in patients with inflammatory rheumatic disease (IRD); in patients with rheumatoid arthritis (RA) treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalised patients with RA. Methods A nationwide cohort study from Denmark between 1 March to 12 August 2020. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals.Further, the incidence of COVID-19 hospitalisation was estimated for patients with RA treated respectively non-treated with TNF-inhibitors, hydroxychloroquine, or glucocorticoids.Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome, or death) among hospital-admitted patients was estimated for RA and non-IRD individudals. Results Patients with IRD (n = 58,052) had an increased partially adjusted incidence of hospitalisation with COVID-19 compared with the 4.5 million people in the general population (HR 1.46, 95%CI 1.15 to 1.86) with strongest associations for patients with RA (n = 29,440, HR 1.72, 95%CI 1.29 to 2.30) and vasculitides (n = 4072, HR 1.82, 95%CI 0.91 to 3.64). There was no increased incidence of COVID-19 hospitalisation associated with TNF-inhibitor, hydroxychloroquine nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI 0.80 to 2.53) for a severe outcome. Conclusion Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalisation.

Incidence and severeness of COVID-19 hospitalization in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark.

Objective In earlier studies, patients with rheumatic and musculoskeletal disease (RMD) who got infected with COVID-19 had a higher risk of mechanical ventilation than comparators. We sought to determine COVID-19 outcomes among patients with RMD 6 months into the pandemic. Methods We conducted a cohort study at Mass General Brigham in Boston, Massachusetts, of patients with RMD matched to up to five comparators by age, sex and COVID-19 diagnosis date (between 30 January 2020 and 16 July 2020) and followed until last encounter or 18 August 2020. COVID-19 outcomes were compared using Cox regression. Risk of mechanical ventilation was compared in an early versus a recent cohort of patients with RMD. Results We identified 143 patients with RMD and with COVID-19 (mean age 60 years; 76% female individuals) and 688 comparators (mean age 59 years; 76% female individuals). There were no significantly higher adjusted risks of hospitalisation (HR: 0.87, 95% CI: 0.68–1.11), intensive care unit admission (HR: 1.27, 95% CI: 0.86–1.86), or mortality (HR: 1.02, 95% CI: 0.53–1.95) in patients with RMD versus comparators. There was a trend towards a higher risk of mechanical ventilation in the RMD cohort versus comparators, although not statistically significant (adjusted HR: 1.51, 95% CI: 0.93–2.44). There was a trend towards improvement in mechanical ventilation risk in the recent versus early RMD cohort (10% vs 19%, adjusted HR: 0.44, 95% CI: 0.17–1.12). Conclusions Patients with RMD and comparators had similar risks of poor COVID-19 outcomes after adjusting for race, smoking and comorbidities. The higher risk of mechanical ventilation in the early RMD cohort was no longer detected in a recent cohort, suggesting improved management over time.

https://ard.bmj.com/content/annrheumdis/80/5/660.full.pdf

Coronavirus disease 2019 outcomes among patients with rheumatic diseases 6 months into the pandemic.

Objective The clinical features of rheumatic patients with coronavirus disease 2019 (COVID-19) have not been reported. This study aimed to describe the clinical features of COVID-19 in rheumatic patients and provide information for handling this situation in clinical practice. Methods This is a retrospective case series study. Deidentified data, including gender, age, laboratory and radiological results, symptoms, signs, and medication history, were collected from 2326 patients diagnosed with COVID-19, including 21 cases in combination with rheumatic disease, in Tongji Hospital between 13 January and 15 March 2020. Results Length of hospital stay and mortality rate were similar between rheumatic and non-rheumatic groups, while the presence of respiratory failure was more common in rheumatic cases (38% vs 10%, p Conclusions Respiratory failure was more common in rheumatic patients infected with COVID-19. Differential diagnosis between COVID-19 and a flare of rheumatic disease should be considered. Trial registration number ChiCTR2000030795.

https://ard.bmj.com/content/annrheumdis/79/8/1007.full.pdf

Clinical features of rheumatic patients infected with COVID-19 in Wuhan, China.

Background: Haploinsufficiency A20 (HA20) is a newly described monogenic disease characterized by a wide spectrum of manifestations and caused by heterozygous mutations in TNFAIP3 which encodes A20 protein. TNFAIP3 mutation leads to disruption of the A20 ovarian tumor (OTU) domain and/or the zinc finger (ZnF) domain. This study aims at exploring the association between the various manifestations of HA20 and different domains disruption of A20. Methods: We reviewed the HA20 cases in previous literature and summarized the clinical features, TNFAIP3 mutation loci and the disrupted domains caused by different sites and patterns of mutations. Patients were classified into three groups according to the A20 domains disruption. Results: A total of 89 patients from 39 families with a genetic diagnosis of HA20 were included. Overall, the age at onset of HA20 was early (median:5.92, IQR:1-10). Patients in the ZnF group showed the earliest onset (median:2.5, IQR:0.6-5), followed by patients in the OTU+ZnF group (median:6, IQR:1-10) and patients in the OTU group (median:10, IQR:8-14). The main manifestations of HA20 patients were recurrent oral ulcers (70%), recurrent fever (42%), gastrointestinal ulcers (40%), skin lesion (38%), genital ulcers (36%), and musculoskeletal disorders (34%). The percentage of patients with musculoskeletal disorders was significantly different among the three groups (p = 0.005). Patients in the OTU+ZnF group and ZnF group were more likely to develop musculoskeletal disorders than patients in the OTU group (p = 0.002 and p = 0.035, respectively). Besides, forty-three percent of HA20 patients were initially diagnosed as Behcet's disease (BD). Compared to the ZnF group, the OTU+ZnF group and OTU group had a higher percentage of patients initially diagnosed as BD (p = 0.006 and p < 0.001, respectively). Conclusion: HA20 is characterized by early-onset and the most common symptoms of HA20 are recurrent oral ulcers, fever and gastrointestinal ulcers. The onset of HA20 in patients with the ZnF domain disruption is earlier than patients with the OTU domain disruption. Compared to the OTU domain, the ZnF domain may be more closely related to musculoskeletal disorders.

/pdf/association-of-clinical-phenotypes-in-haploinsufficiency-a20-3zv9r3rhgd.pdf

Association of Clinical Phenotypes in Haploinsufficiency A20 (HA20) With Disrupted Domains of A20.

Objective This study aimed to assess the disease conditions of patients with inflammatory bowel disease (IBD) in Hubei Province during the outbreak of Coronavirus Disease 2019 (COVID-19) by questionnaire online and guide their self-management during this epidemic. Results A total of 102 eligible questionnaires were included. No patient we surveyed reported a diagnosis of COVID-19. Our result showed that 67.86% of patients with ulcerative colitis (UC) and 80.43% of patients with Crohn's disease (CD) were in remission, 85.29%of patients had a good quality of life. Part of the patients (21.57%) reported their disease conditions worsening. The reduction in physical exercise was a risk factor for worsening conditions (OR=17.593, p=0.009). Some patients reported an alteration of medication regimens during the epidemic. Conclusions The epidemic of COVID-19 might have a certain impact on many aspects of Hubei IBD patients within four weeks after the traffic control. Doctors could utilize the results from our questionnaire to guide IBD patients' self-management. Methods A questionnaire was designed containing the Harvey-Bradshaw Index (HBI), the 6-point Mayo Score, the short inflammatory bowel disease questionnaire (SIBDQ) and distributed to Hubei IBD patients online within four weeks of traffic control after the outbreak, it also included questions about patients' self-reported disease conditions and their epidemiological features of COVID-19.

Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019.

Objective: Intestinal Behcet's disease (iBD) is an autoimmune disorder diagnosed by typical intestinal ulcers and systemic Behcet's disease (BD) manifestations. Haploinsufficiency of A20 (HA20) is a recently described autoinflammatory disease with a phenotype resembling BD, caused by heterozygous loss-of-function mutations in TNFAIP3 gene (encoding A20). Methods: We described a 29-year-old female with iBD-like symptoms including relapsing ulceration of intestinal anastomosis, recurrent oral ulcers and vasculitis in extremities. Due to the atypical intestinal ulcers with long segmental involvement and intestinal obstruction, whole exome sequencing (WES) was performed to screen for the underlying genetic defect and the identified gene was confirmed by Sanger sequencing. The expression levels of A20 was evaluated by Western blot. Sanger sequencing and Western blot were also performed in the patient's family members. Results: A heterozygous mutation of TNFAIP3 (c.305A>G, p. Asn 102 Ser) was identified in the patient. The identical TNFAIP3 mutation was also found in her father and brother who had suffered from recurrent oral ulcers since childhood. Functional experiments revealed that the expression of A20 was decreased in the peripheral blood mononuclear cells of the patient and her family members who carried the TNFAIP3 mutation. Conclusion: We described a Chinese patient with a novel heterozygous mutation in TNFAIP3 who developed iBD-like symptoms. We proposed that the TNFAIP3 heterozygous mutation (c.305A>G, p. Asn 102 Ser) with an insufficient expression of A20 may be associated with the iBD phenotype in patients.

Yu Chen

Papers

Clinical features of rheumatic patients infected with COVID-19 in Wuhan, China.

Association of Clinical Phenotypes in Haploinsufficiency A20 (HA20) With Disrupted Domains of A20.

Questionnaire assessment helps the self-management of patients with inflammatory bowel disease during the outbreak of Coronavirus Disease 2019.

A20 Haploinsufficiency in a Chinese Patient With Intestinal Behcet's Disease-Like Symptoms: A Case Report.

Clinical characteristics of IgG4-RD patients infected with COVID-19 in Hubei, China.