No genetic causal association between systemic lupus erythematosus and COVID-19.

Objective: Emerging evidence suggests an increased prevalence of coronavirus disease 2019 (COVID-19) in patients with systemic lupus erythematosus (SLE), the prototype of autoimmune disease, compared to the general population. However, the conclusions were inconsistent, and the causal relationship between COVID-19 and SLE remains unknown. Methods: In this study, we aimed to evaluate the bidirectional causal relationship between COVID-19 and SLE using bidirectional Mendelian randomization (MR) analysis, including MR-Egger, weighted median, weighted mode, and the inverse variance weighting (IVW) method. Results: The results of IVW showed a negative effect of SLE on severe COVID-19 (OR = 0.962, p = 0.040) and COVID-19 infection (OR = 0.988, p = 0.025), which disappeared after Bonferroni correction. No causal effect of SLE on hospitalized COVID-19 was observed (OR = 0.983, p = 0.148). In the reverse analysis, no causal effects of severe COVID-19 infection (OR = 1.045, p = 0.664), hospitalized COVID-19 (OR = 0.872, p = 0.109), and COVID-19 infection (OR = 0.943, p = 0.811) on SLE were found. Conclusion: The findings of our bidirectional causal inference analysis did not support a genetically predicted causal relationship between SLE and COVID-19; thus, their association observed in previous observational studies may have been caused by confounding factors.

Post-COVID-19 depression and anxiety in patients with systemic lupus erythematosus.

OBJECTIVES: This study aimed to evaluate depression and anxiety in patients with systemic lupus erythematosus (SLE) in the post-coronavirus disease-2019 (COVID-19) period and their potential association with the disease activity and related organ damage. PATIENTS AND METHODS: This is a case-control study including 120 adult Egyptian patients with SLE: sixty patients with SLE who were proven previously to be positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR) and recovered during the 3 months prior to the study were included in the case group and an equal number of age- and sex-matched patients with SLE and no evidence of SARS-CoV-2 infection were included in the control group. Patients' clinical history was collected, and they underwent clinical evaluation, including SLE disease activity, damage assessment, and psychological assessment. RESULTS: The mean depression and anxiety scores were significantly higher in cases than in the control group. Both scores showed a significant positive correlation with age, disease duration, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index for SLE (SDI), and SLE disease activity index (SLEDAI) and a significant negative correlation with education years. Hierarchical multivariate regression analyses revealed that COVID-19 infection was a predictor for severe depression and moderate-to-severe anxiety. CONCLUSIONS: Patients with SLE, who are already vulnerable to physiological stressors, are especially predisposed to more risk of anxiety and depression when they are contracted with COVID-19 disease. Furthermore, anxiety and depression are associated with SLE activity and damage scores, and COVID-19 infection is a significant predictor for their severity. These results suggest that healthcare providers should give special attention to the mental health of SLE patients, especially during the COVID-19 pandemic.

Recalcitrant Cutaneous Lupus Erythematosus during COVID-19 Pandemic: A Case Report.

A 30-year-old woman visited the dermatology and venereology clinic with red rashes on her cheeks with spreading wounds to the ears present for 6 months. Similar ailments were also found on the chest and upper arms accompanying black spots on both palms. Initially, red rashes appeared intermittently, observed around the eyes and cheeks, especially at sun exposure. Tenderness or pruritus was not present; however, the patient had joints ache, sore fingers, hair loss as well as frequent fever.

In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature.

BACKGROUND: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. CASE PRESENTATION: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. CONCLUSIONS: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Risk of COVID-19 among unvaccinated and vaccinated patients with systemic lupus erythematosus: a general population study.

OBJECTIVE: To compare the risk of SARS-CoV-2 infection and its related severe sequelae between patients with systemic lupus erythematosus (SLE) and the general population according to COVID-19 vaccination status. METHODS: We performed cohort studies using data from The Health Improvement Network to compare the risks of SARS-CoV-2 infection and severe sequelae between patients with SLE and the general population. Individuals aged 18-90 years with no previously documented SARS-CoV-2 infection were included. We estimated the incidence rates and HRs of SARS-CoV-2 infection and severe sequelae between patients with SLE and the general population according to COVID-19 vaccination status using exposure score overlap weighted Cox proportional hazards model. RESULTS: We identified 3245 patients with SLE and 1 755 034 non-SLE individuals from the unvaccinated cohort. The rates of SARS-CoV-2 infection, COVID-19 hospitalisation, COVID-19 death and combined severe outcomes per 1000 person-months were 10.95, 3.21, 1.16 and 3.86 among patients with SLE, and 8.50, 1.77, 0.53 and 2.18 among general population, respectively. The corresponding adjusted HRs were 1.28 (95% CI: 1.03 to 1.59), 1.82 (95% CI: 1.21 to 2.74), 2.16 (95% CI: 1.00 to 4.79) and 1.78 (95% CI: 1.21 to 2.61). However, no statistically significant differences were observed between vaccinated patients with SLE and vaccinated general population over 9 months of follow-up. CONCLUSION: While unvaccinated patients with SLE were at higher risk of SARS-CoV-2 infection and its severe sequelae than the general population, no such difference was observed among vaccinated population. The findings indicate that COVID-19 vaccination provides an adequate protection to most patients with SLE from COVID-19 breakthrough infection and its severe sequelae.

Pediatric Systemic Lupus Erythematous in COVID-19 Era.

Pediatric systemic lupus erythematosus is a chronic autoimmune disorder with a highly variable course and prognosis. It results in functional abnormalities in the immune system due to intrinsic factors and the use of immunosuppressive therapies associated with underlying comorbidities seem to increase the risk of severe COVID-19 and poor outcomes of the disease in pediatric systemic lupus erythematosus (SLE) patients. The aim of this review is to obtain a better understanding of the existing link between this new viral infection and pediatric lupus. We have analyzed the characteristics of newly diagnosed cases of pediatric SLE following COVID-19 which have been reported in the literature and which describe the impact that COVID-19 has on patients already suffering with pediatric SLE.

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.

Incidence of rheumatic diseases during the COVID-19 pandemic in South Korea.

BACKGROUND/AIMS: The recent coronavirus disease 2019 (COVID-19) pandemic has been associated with changes in the epidemiology of not only infectious diseases but also several non-infectious conditions. This study investigated changes in the recorded incidence of various rheumatic diseases during the COVID-19 pandemic. METHODS: The number of patients for each disease from January 2016 to December 2020 was obtained from the Korean Health Insurance Review and Assessment Service database. We compared the incidence of nine rheumatic diseases (seropositive rheumatoid arthritis, systemic lupus erythematosus [SLE], idiopathic inflammatory myositis [IIM], ankylosing spondylitis [AS], systemic sclerosis, Sjögren's syndrome, Behçet's disease [BD], polymyalgia rheumatica, and gout) and hypertensive diseases to control for changes in healthcare utilisation before and after the COVID-19 outbreak. The disease incidence before and after the COVID-19 outbreak was compared using the autoregressive integrated moving average (ARIMA) and quasi- Poisson analyses. RESULTS: Compared with the predicted incidence in 2020 using the ARIMA model, the monthly incidence of SLE, BD, AS, and gout temporarily significantly decreased, whereas other rheumatic diseases and hypertensive diseases were within the 95% confidence interval (CI) of the predicted values in the first half of 2020. In age- and sex-adjusted quasi-Poisson regression analysis, the annual incidences of IIM (rate ratio [RR], 0.473; 95% CI, 0.307 to 0.697), SLE (RR, 0.845; 95% CI, 0.798 to 0.895), and BD (RR, 0.850; 95% CI, 0.796 to 0.906) were significantly decreased compared with those in the previous 4 years. CONCLUSION: The recorded annual incidence of some rheumatic diseases, including IIM, SLE, and BD, decreased during the COVID-19 pandemic.

Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Two cases of systemic lupus erythematosus after administration of severe acute respiratory syndrome coronavirus 2 vaccine.

Although there is a great demand for increased coronavirus disease 2019vaccination worldwide, rare side effects of the vaccines in susceptible individuals are attracting attention. We recently treated two patients who developed systemic lupus erythematosus after administration of a severe acute respiratory syndrome coronavirus 2 vaccine from Pfizer-BioNTech or Moderna. While causal relationships between vaccination and adverse events are difficult to discern due to both confounding and masking factors, our findings suggest that attention to possible adjuvant-related autoimmune diseases in certain individuals receiving severe acute respiratory syndrome coronavirus 2 vaccines is appropriate.

The Profile of COVID-19 in Patients with Autoimmune Disease: A Case Series.

Autoimmune diseases are known to be a risk factor for severe COVID-19 infection. This is the first case series of patients with autoimmune disease suffering from COVID-19 infection in Jakarta, Indonesia. There were 12 confirmed cases of COVID-19 infection in autoimmune patients from March 2020 until February 2021. We select 5 patients in this case series. Three of them had systemic lupus erythematous (SLE), one of them had rheumatoid arthritis, and one of them had ankylosing spondylitis. Three of them had high BSR Risk Stratification. Most of them had used daily steroid therapy. Fatigue, abdominal pain, diarrhea, and cough were the common symptoms found.  None of the patients were admitted to ICU, used mechanical ventilators, and all of them survived. Most of the patients were prescribed anti-coagulant therapy. This first comprehensive case series can provide valuable information regarding the clinical characteristics of COVID-19 infection in the Indonesian autoimmune disorder patient population.

Outcomes of Filipinos with inflammatory rheumatic diseases developing COVID-19 prior to vaccinations and new variants: a historical perspective.

We described the profile and outcome of Filipino patients with inflammatory rheumatic diseases (IRDs) who developed COVID-19 (IRD-C19) during the onset of the pandemic, prior to vaccinations and variants. We obtained de-identified data of Filipino patients with IRD-C19 from the Global Rheumatology Alliance registry from March 2020 to August 2021. Descriptive statistics and multivariate analyses were applied. Registered were 164 patients (mean age 44 years; 70% female). The most common IRDs were systemic lupus erythematosus (SLE, 41.4%), rheumatoid arthritis (RA, 15.2%), and gout (14.6%). Majority were receiving conventional DMARDs (59.1%) and/or glucocorticoid therapy (GC, 51.2%). Half (58.5%) were hospitalized, with risk higher in active IRD (OR 3.7), heart disease (8.52), and hypertension (8.73); and lower in SLE patients (0.15). Among hospitalized patients, 76% needed supplemental oxygen. Heart disease (6.28), hypertension (7.6), and moderate-to-high IRD activity (3.37) were associated with higher odds of requiring oxygen supplementation. Hypertension was associated with mechanical ventilation (8.23). Twenty-four (15%) patients died, with odds lower if on prednisone ≥ 10 mg/day (0.17) and with other autoimmune IRDs aside from SLE and RA (0.05). Among patients with IRD-C19 prior to vaccinations and variants, higher disease activity, hypertension, and heart disease were associated with poorer outcomes. Prednisone ≥ 10 mg/day was associated with lower odds of death. This study provides valuable historical information, emphasizing the need for continued data collection to clarify COVID-19's impact.

Short- and mid-term outcomes in systemic lupus erythematosus patients presenting with disease exacerbation after SARS-CoV-2 mRNA vaccination: A cohort study from Puerto Rico.

OBJECTIVE: To determine if SARS-CoV-2 mRNA vaccination has an impact on the clinical course of systemic lupus erythematosus (SLE). METHODS: Puerto Ricans with SLE who received mRNA COVID-19 vaccines were studied. Demographic parameters, clinical manifestations, disease activity (per Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), disease damage (per Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), emergency room visits, hospitalizations, and pharmacologic therapy were determined. Baseline variables (prior to vaccination) were compared between patients with and without exacerbation after SARS-CoV-2 vaccination. Among those with exacerbation, clinical outcomes were determined up to 1 year after vaccination. RESULTS: Of the entire cohort (n = 247), 14 (5.7%) had post-vaccination exacerbations. Photosensitivity, oral ulcers, anti-Ro antibodies, higher SLEDAI score, and corticosteroids exposure were associated with post-vaccination flares. Among those with post-vaccination flares, 10 (71.4%) had major organ involvement. No significant differences were observed for mean SLEDAI scores, emergency room visits, hospitalizations, disease damage, and exposure to immunosuppressive drugs before and after SARS-CoV-2 mRNA vaccination. At 12 months of follow-up, all patients were fully controlled without evidence of active disease. CONCLUSION: In our group of SLE patients, 5.7% had a disease flare after SARS-CoV-2 mRNA vaccination. Most had exacerbations involving major organs/systems. Mucocutaneous manifestations, anti-Ro antibodies, disease activity, and corticosteroids were associated with flares. Awareness of these factors and the possibility of a major lupus flare after vaccination with COVD-19 vaccines is critical to provide timely and effective therapy.

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.

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.