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.

Systemic lupus erythematosus myocarditis after COVID-19 vaccination.

INTRODUCTION: Cases of acute myocarditis have been after administration of the BNT162b2 and Ad26.COV2.S vaccine. OBJECTIVE: Describe another possible mechanism of myocarditis after COVID-19 vaccination. CASE PRESENTATION: We describe the clinical case of a 72-year-old female with pleuritic chest pain one week after the third of the BNT162b2 mRNA vaccine. Serological tests for cardiotropic pathogens were negative, and autoimmunity screening was positive with anti-nuclear antibody (ANA) in 1:160 dilution, Anti-double-stranded DNA (anti-dsDNA), and anti-histone antibodies. 18F-fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) showed a focal myocardial and pericardial inflammatory process in the cardiac apex. RESULTS AND DISCUSSION: Systemic lupus erythematosus (SLE) diagnosis was made with myocardial affection. As far as we know, this is the first report of a case of lupus myocarditis after the COVID-19 vaccine. CONCLUSION: Given the pathogenic rationales, the association between SLE and myocarditis should be considered.

A case of systemic lupus erythematosus presenting with intestinal lymphangiectasia-associated protein-losing enteropathy accompanying hyperinflammation.

Systemic lupus erythematosus (SLE) has the potential to affect virtually every organ; however, gastrointestinal system manifestations are relatively rare compared to other autoimmune diseases such as systemic sclerosis and inflammatory bowel disease. A 29-year-old female patient attended to the emergency room with abdominal distention, acute onset abdominal pain and constipation. She had watery chronic diarrhea (4-5 times/d) and weight loss (6 kg, 12%) for 4 months. While there was increased intestinal wall thickness, air-liquid levels were shown on abdomen computed tomography scan. The patient underwent abdominal surgery due to diagnosis of ileus. Ileocecal resection was performed and pathologic evaluation revealed intestinal lymphangiectasia. Autoimmune serology was performed with the following resulats: anti-nuclear antibody 1/3200 with homogenous pattern, anti-DNA antibody and anti-Sm/ribonucleoprotein antibodies were positive in addition to low complement levels (C3: 0.28 [0.9-1.8 g/L], C4: 0.06 [0.1-0.4 g/L]) indicating diagnosis of SLE. Development of intestinal involvement in SLE (lupus enteritis) is mainly grouped into 3 headings such as mesenteric vasculitis, pseudo-obstruction, and protein-losing enteropathy. Although the pathogenesis of intestinal lymphangiectasia remains unknown, it has been reported that immune complex-mediated visceral vasculitis may result in bowel wall and mucosal edema. To our knowledge this is the first case report accompanying hyperinflammatory response in addition to intestinal lymphangiectasia in SLE. On the other hand, clinicians should be alert for other reasons for hyperinflammatory syndromes rather than COVID-19, even during the pandemic.

SARS-CoV-2 vaccine-triggered conversion from systemic lupus erythematosus (SLE) to bullous SLE and dipeptidyl peptidase 4 inhibitors-associated bullous pemphigoid.

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease in patients with SLE. BSLE is a heterogenous disease caused by autoantibodies to the basement membrane, mainly type VII collagen. The pathogenesis of the development of autoantibodies in BSLE remains unknown. We report a case of SLE taking dipeptidyl peptidase 4 inhibitors (DPP4i) who developed tense blister lesions after administration of SARS-CoV-2 vaccine. Initial erythematous lesion before administration of SARS-CoV-2 vaccine had not shown IgG deposition at basement membrane both direct and indirect immunofluorescence (IIF). However, the result of those examinations became positive after the administration of SARS-CoV-2 vaccine. Furthermore, IIF test results using NaCl split skin had shown positive against epidermal side. These observations suggest that SARS-CoV-2 vaccination triggered production of autoantibodies that cause bullous SLE. The present case fulfills the diagnostic criteria for both BSLE and DPP4i-associated bullous pemphigoid. Skin lesions were cleared after withdrawal of DPP4i. Therefore, physicians should ask patients who develop blisters after the vaccination whether they are taking DPP4i.

The Role of Immunosuppression in the Development of COVID-19 in Systemic Lupus Erythematosus Patients: A Brief Report.

Recently, due to the coronavirus disease 2019 (COVID-19) pandemic, much concern has been raised about patients with chronic diseases who may become more susceptible to the disease. The present cross-sectional study aimed to characterize the clinical course of COVID-19 in patients with systemic lupus erythematosus (SLE). In addition, a possible correlation between the immunosuppression state and the incidence of COVID-19 is investigated. In May 2020, 500 SLE patients registered in the database of Golestan Rheumatology Research Center (Golestan province, Iran) were selected for this cross-sectional study. Using a questionnaire, patients were contacted by telephone to collect data including demographic characteristics, disease status, drug use, and new clinical symptoms. Data were analyzed using SPSS software version 24.0. Of the 500 selected patients, 355 responded to the phone calls and subsequently enrolled in the study. Among the enrolled patients, 25 were classified as COVID-19 positive, including eight hospitalized patients, of which two required intensive care and subsequently died. COVID-19 incidence was significantly lower in the immunosuppressed patients (2.2% vs. 10%, P=0.01). There was no significant correlation between hydroxychloroquine consumption and the incidence of COVID-19 in SLE patients. Fever, fatigue, dyspnea, and dry cough were the most common clinical symptoms. Our results showed that COVID-19 incidence was lower in immunosuppressed than the non-immunosuppressed SLE patients. Further studies are required to substantiate the role of immunosuppression in the development of COVID-19. A preprint version of this study was published at https://www.researchsquare.com/article/rs-78704/v1 with doi: https://doi.org/10.21203/rs.3.rs-78704/v1.

Peripheral Ulcerative Keratitis in a Young Lady with Systemic Lupus Erythematosus Post Rituximab Infusion-A Case Report.

AIM: We report a new ocular finding of episcleritis (OD) and peripheral ulcerative keratitis (OS) in a 40-year-old lady with a 13-year history of systemic lupus erythematosus (SLE), 3 weeks post-rituximab infusion. MATERIALS & METHODS: Retrospective case report. RESULTS: A 40-year-old lady with a history of SLE and 3 weeks post rituximab infusion developed a new onset episcleritis (OD) and peripheral ulcerative keratitis (OS). As the PUK continued to advance with a leading edge, intravenous methyl prednisolone 1 gm/day was given for 3 days followed by a slow tapering course of oral prednisolone 50 mg/day. Though her ocular inflammation resolved, she developed pneumonia 6 weeks later. At 10 months follow-up, there were no ocular recurrences. She is currently on mycophenolate mofetil 2 gm/day along with oral prednisolone of 10 mg/day. CONCLUSION: This case highlights the new occurrence of episcleritis and PUK in SLE post-rituximab infusion.

COVID-19 diversity: A case of multisystem inflammatory syndrome in children masquerading as juvenile systemic lupus erythematosus.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term 'multisystem inflammatory syndrome in children (MIS-C)'. A one and half-year-old girl, admitted to Mansoura University Children's Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy. Moreover, bicytopenia, positive antinuclear, anti-double-stranded DNA antibodies and low C3 qualified her as a case of juvenile SLE. Despite the child received the initial therapy of immunosuppressive medication, her general condition deteriorated with fever persistence and rash exacerbation. At that time, the skin of her hands and feet started to peel. Thus, an expanded study for other alternatives was obligatory; SARS-CoV-2 infection testing revealed positive IgG serology, and retesting for lupus autoantibodies turned negative. HRCT chest showed bilateral basal consolidation with ground-glass appearance. Furthermore, Echo exhibited coronary artery dilation with thrombus inside. This evolution raised the concern for COVID-related MIS-C syndrome. This report provides a model of COVID-19 heterogeneity with protean immune-related manifestations. This case has a unique presentation that necessities its description, in order to provide a nidus for future studies in this new entity.

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.

New-onset systemic lupus erythematosus following BNT162b2 mRNA COVID-19 vaccine: a case series and literature review.

Emerging data evaluated the possible link between the Coronavirus 19 (COVID-19) vaccine and acute flares of rheumatic autoimmune diseases. However, the association between the COVID-19 vaccine and the development of de-novo rheumatic autoimmune diseases remained unclear. We report the first case series of three male patients who developed new-onset systemic lupus erythematosus following receiving Pfizer BNT162b2 mRNA vaccination. The clinical characteristics share some similarities with drug-induced lupus. More patients with SLE following COVID-19 may be diagnosed in the future. Additional studies will provide more significant insights into the possible immunogenic influence of the COVID-19 vaccine.

Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis.

Introduction: Urine-soluble CD163 (usCD163) is released from alternatively activated macrophages involved in the resolution of inflammation in glomeruli and plays an important role in glomerulonephritis. This study explored the role of usCD163 in patients with systemic lupus erythematosus (SLE). Materials and Methods: usCD163 concentrations were measured cross-sectionally in 261 SLE patients in Taiwan. Clinical and laboratory data were collected, and SLE disease activity scores were calculated to assess the correlation with usCD163. Results: SLE patients with high usCD163 levels tended to be younger, with a higher hospital admission rate, higher prednisolone dose, lower estimated glomerular filtration rate, higher urine protein creatinine ratio (UPCR), more pyuria and hematuria, higher levels of inflammatory markers, higher rates of anemia, neutropenia, and lymphopenia, lower complement 3 (C3) levels, higher anti-double-stranded DNA antibody (anti-dsDNA Ab) levels, and higher disease activity scores (p < 0.05). usCD163 levels were significantly higher in patients with active lupus nephritis (LN) than in those with extrarenal or inactive SLE and correlated with UPCR, disease activity, and anti-dsDNA Ab levels. SLE patients with high usCD163 levels tended to have a higher chronic kidney disease stage. Discussion and conclusion: The usCD163 level correlates with the severity of LN and disease activity in renal SLE.

A case report of pediatric systemic lupus erythematosus with diffuse alveolar hemorrhage following COVID-19 infection: Causation, association, or chance?

RATIONALE: Diffuse alveolar hemorrhage (DAH) is a rare manifestation of childhood systemic lupus erythematosus (SLE) that can be life-threatening. Several reports have linked previous or concurrent coronavirus disease (COVID-19) infections with a high prevalence of autoimmune and autoinflammatory disorders. PATIENT CONCERNS: We report a case of a 13-year-old female who presented with DAH due to SLE 2 months after a laboratory-confirmed severe COVID-19 infection. DIAGNOSES: The patient was diagnosed with DAH due to SLE 2 months after a laboratory-confirmed severe COVID-19 infection. INTERVENTIONS AND OUTCOMES: The patient was treated with intravenous methylprednisolone pulse, broad-spectrum antibiotics, and supportive measures. In addition, she received 6 sessions of plasma exchange and maintenance methylprednisolone therapy (2 mg/kg/day). The patient then improved and was discharged on prednisolone, hydroxychloroquine, and azathioprine. LESSONS: We suggest plasmapheresis be considered a treatment for SLE-associated DAH in the context of active disease when conventional treatment has failed to induce a rapid response. In addition, further studies are needed to assess the role of COVID-19 as an autoimmune disease trigger, particularly for SLE.

Medium-term impact of the SARS-CoV-2 mRNA vaccine against disease activity in patients with systemic lupus erythematosus.

OBJECTIVES: Numerous case reports have referred to new onset or flare of SLE after SARS-CoV-2 messenger RNA (mRNA) vaccines. Several observational studies showed that the short-term flare rate of SLE after SARS-CoV-2 vaccination is low. However, well-controlled clinical surveys are unavailable and the medium-term impact of the SARS-CoV-2 mRNA vaccines against the flare of SLE is uncertain. Therefore, we aimed to analyse the association between vaccination and medium-term subjective and objective disease activities of SLE and flares using matched pair methods. METHODS: Altogether, 150 patients with SLE from the Kyoto Lupus Cohort were included. Patients who received two doses of the SARS-CoV-2 mRNA vaccines were 1:1 matched with unvaccinated patients based on the first vaccination date. The outcome measures were the SLE Disease Activity Index-2000 (SLEDAI-2K), the Japanese version of the SLE Symptom Checklist Questionnaire (SSC-J) and the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index at 30, 60 and 90 days after vaccination. RESULTS: SLEDAI-2K levels were not significantly different in vaccinated and unvaccinated patients with SLE at 30, 60 and 90 days after the second vaccination (adjusted estimate (95% CI): 30 days: -0.46 (-1.48 to 0.56), p=0.39; 60 days: 0.38 (-0.64 to 1.40), p=0.47; 90 days: 0.40 (-0.54 to 1.34), p=0.41). Similar results were observed in the SSC-J score (adjusted estimate (95% CI), 30 days: 0.05 (-1.46 to 1.56), p=0.95; 60 days: -0.63 (-2.08 to 0.82), p=0.40; 90 days: 0.27 (-1.04 to 1.58), p=0.69) and flare index (adjusted OR (95% CI), 30 days: 0.81 (0.36 to 1.85), p=0.62; 60 days: 1.13 (0.50 to 2.54), p=0.77; 90 days: 0.85 (0.32 to 2.26), p=0.74). CONCLUSION: SARS-CoV-2 vaccination did not significantly influence the medium-term subjective and objective disease activities or flares of SLE until 90 days after the second vaccination.

One year in review 2022: systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis. New insights in SLE about pathogenetic pathways, biomarkers, and data on clinical manifestations are progressively emerging, and new drugs and new therapeutic strategies have been proposed to improve the control of disease activity. Thus, this review is aimed to summarise the most relevant data about SLE emerged during 2021, following the previous annual review of this series.

Identification of Diagnostic Gene Markers and Immune Infiltration in Systemic Lupus.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs, with atypical clinical manifestations and indefinite diagnosis and treatment. So far, the etiology of the disease is not completely clear. Current studies have known the interaction of genetic system, endocrine system, infection, environment, and other factors. Due to abnormal immune function, the human body, with the participation of various immune cells such as T cells and B cells, abnormally recognizes autoantigens, so as to produce a variety of autoantibodies and combine them to form immune complexes. These complexes will stay in the skin, kidney, serosa cavity, large joints, and even the central nervous system, resulting in multisystem damage of the body. The disease is heterogeneous, and it can show different symptoms in different populations and different disease stages; patients with systemic lupus erythematosus need individualized diagnosis and treatment. Therefore, we aimed to search for SLE immune-related hub genes and determine appropriate diagnostic genes to provide help for the detection and treatment of the disease. Methods: Gene expression data of whole blood samples of SLE patients and healthy controls were downloaded from the GEO database. Firstly, we analyzed and identified the differentially expressed genes between SLE and the normal population. Meanwhile, the single-sample gene set enrichment analysis (ssGSEA) was used to identify the activation degree of immune-related pathways based on gene expression profile of different patients, and weighted gene coexpression network analysis (WGCNA) was used to search for coexpressed gene modules associated with immune cells. Then, key networks and corresponding genes were found in the protein-protein interaction (PPI) network. The above corresponding genes were hub genes. After that, this study used receiver operating characteristic (ROC) curve to evaluate hub gene in order to verify its ability to distinguish SLE from the healthy control group, and miRNA and transcription factor regulatory network analyses were performed for hub genes. Results: Through bioinformatics technology, compared with the healthy control group, 2996 common differentially expressed genes (DEGs) were found in SLE patients, of which 1639 genes were upregulated and 1357 genes were downregulated. These differential genes were analyzed by ssGSEA to obtain the enrichment fraction of immune-related pathways. Next, the samples were selected by WGCNA analysis, and a total of 18 functional modules closely related to the pathogenesis of SLE were obtained. Thirdly, the correlation between the above modules and the enrichment fraction of immune-related pathways was analyzed, and the turquoise module with the highest correlation was selected. The 290 differential genes of this module were analyzed by GO and KEGG. The results showed that these genes were mainly enriched in coronavirus disease (COVID-19), ribosome, and human T cell leukemia virus 1 infection pathway. The 290 DEGs with PPI network and 28 genes of key networks were selected. ROC curve showed that 28 hub genes are potential biomarkers of SLE. Conclusion: The 28 hub genes such as RPS7, RPL19, RPS17, and RPS19 may play key roles in the advancement of SLE. The results obtained in this study can provide a reference in a certain direction for the diagnosis and treatment of SLE in the future and can also be used as a new biomarker in clinical practice or drug research.

New-onset lupus nephritis associated with COVID-19 infection.

A dysregulated immune response plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Environmental factors such as viruses, including coronavirus 2 (COVID-19), have been described to play a role in SLE presentation and exacerbation. These viruses trigger a host's humoral and cellular immunities typically essential in elimination of the viral infection. We present a case of a Hispanic male who developed new-onset lupus nephritis class II after a COVID-19 infection.

Systemic lupus erythematosus: overview, management and COVID-19.

Systemic lupus erythematosus is a complex multi-system disease affecting various systems of the body. The aetiology remains unclear; however, it is thought that immune system dysregulation, environmental factors and viral susceptibility can trigger the disease. Mortality remains high due to cardiovascular disease, infection and lupus nephritis. Clinical assessment should comprise an extensive history, detailed physical examination and relevant laboratory tests. Management begins with an in-depth understanding of disease-specific complications and associated comorbidities. Treatments should be based on a shared decision-making process between the patient and the clinician. Review by a specialist nurse is vital for ongoing support and education. Current treatments can increase the risk of COVID-19 infection and disease severity, so caution is needed in the current climate. New treatments are emerging and offer hope to those with refractory disease.