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.

The COVID-19 epidemic curve and vaccine acceptance among patients with rheumatic diseases: an ecological study.

The attitudes toward emerging COVID-19 vaccines have been of great interest worldwide, especially among vulnerable populations such as patients with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to analyze the relationship between the nationwide number of COVID-19 cases and deaths, and vaccine acceptance or hesitancy of patients with RMDs from four patient care centers in Mexico. Furthermore, we explored differences in acceptance according to specific diagnoses: rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This ecological study was a secondary analysis of a cross-sectional study using a validated questionnaire to measure vaccine acceptance. We generated a global Likert scale to evaluate overall attitudes toward the COVID-19 vaccine. We analyzed data from 1336 patients from March to September 2021: 85.13% (1169) were women, with a mean age of 47.87 (SD 14.14) years. The most frequent diagnoses were RA (42.85%, 559) and SLE (27.08%, 393). 635(47.52%) patients were unvaccinated, 253(18.93%) had one dose and 478(35.77%) had two doses. Of all participating patients, 94% were accepting toward the COVID-19 vaccine. Vaccine acceptance remained consistently high throughout the study. However, differences in vaccine acceptance are identified when comparing diagnoses. The peak of the national epidemic curve coincided with an increase in hesitancy among patients with RA. Contrastingly, patients with SLE became more accepting as the epidemic curve peaked. Mexican patients show high acceptance of the COVID-19 vaccine, influenced in part by a patient's specific diagnosis. Furthermore, vaccine acceptance increased mirroring the curve of COVID-19 cases and deaths in the country. This should be taken into consideration when updating recommendations for clinical practice.

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.

Genetic predisposition between coronavirus disease 2019 and rheumatic diseases: A 2-sample Mendelian randomization study.

OBJECTIVE: The causalities between the coronavirus disease 2019 (COVID-19) and the risk of rheumatic diseases remain unclear. The purpose of this study was to investigate the causal effect of COVID-19 on rheumatic disease occurrence. METHODS: Single nucleotide polymorphisms (SNPs), acquired from published genome-wide association studies, were used to perform 2-sample Mendelian randomization (MR) on cases diagnosed with COVID-19 (n = 13 464), rheumatic diseases (n = 444 199), juvenile idiopathic arthritis (JIA, n = 15 872), gout (n = 69  374), systemic lupus erythematosus (SLE, n = 3094), ankylosing spondylitis (n = 75 130), primary biliary cholangitis (PBC, n = 11 375) and primary Sjögren's syndrome (n = 95 046). Three MR methods were used in the analysis based on different heterogeneity and pleiotropy using the Bonferroni correction. RESULTS: The results revealed a causality between COVID-19 and rheumatic diseases with an odds ratio (OR) of 1.010 (95% confidence interval [CI], 1.006-1.013; P = .014). In addition, we observed that COVID-19 was causally associated with an increased risk of JIA (OR 1.517; 95%CI, 1.144-2.011; P = .004), PBC (OR 1.370; 95%CI, 1.149-1.635; P = .005), but a decreased risk of SLE (OR 0.732; 95%CI, 0.590-0.908; P = .004). Using MR, 8 SNPs were identified to associate with COVID-19 and recognized as significant variables. None of them were previously reported in any other diseases. CONCLUSIONS: This is the first study to use MR to explore the impact of COVID-19 on rheumatic diseases. From a genetic perspective, we found that COVID-19 could increase the risk of rheumatic diseases, such as PBC and JIA, but decrease that of SLE, thereby suggesting a potential surge in the disease burden of PBC and JIA following the COVID-19 pandemic.

Systemic Lupus Erythematosus Risk: The Role of Environmental Factors.

Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease. The etiology of SLE is multifactorial and includes potential environmental triggers, which may occur sequentially (the "multi-hit" hypothesis). This review focuses on SLE risk potentially associated with environmental factors including infections, the microbiome, diet, respirable exposures (eg, crystalline silica, smoking, air pollution), organic pollutants, heavy metals, and ultraviolet radiation.

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.

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic.

OBJECTIVE: We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. METHODS: Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. RESULTS: Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. CONCLUSIONS: Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Update on antimalarials and systemic lupus erythematosus.

PURPOSE OF REVIEW: The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). RECENT FINDINGS: New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. SUMMARY: Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.

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.

Study of common hypertriglyceridaemia genetic variants and subclinical atherosclerosis in a group of women with SLE and a control group.

OBJECTIVE: SLE is associated with increased cardiovascular risk (CVR). High serum concentrations of triglyceride-rich lipoproteins and apolipoprotein B-rich particles constitute the characteristic dyslipidaemia of SLE. METHODS: A cross-sectional study was conducted to study the relationship between genetic variants involved in polygenic hypertriglyceridaemia, subclinical atherosclerosis and lipoprotein abnormalities. 73 women with SLE and 73 control women age-matched with the case group were recruited (age range 30-75 years). Serum analysis, subclinical atherosclerosis screening studies for the detection of plaque, and genetic analysis of the APOE, ZPR1, APOA5 and GCKR genes were performed. RESULTS: Triglyceride concentrations and the prevalence of hypertension, dyslipidaemia and carotid atherosclerosis were higher in women with SLE than in the control group. Multivariate logistic regression showed that CC homozygosity for the GCKR rs1260326 gene (OR=0.111, 95% CI 0.015 to 0.804, p=0.030) and an increase of 1 mmol/L in triglyceride concentrations were associated with a greater risk of carotid plaque in women with SLE (OR=7.576, 95% CI 2.415 to 23.767, p=0.001). CONCLUSIONS: GCKR CC homozygosity (rs1260326) and serum triglyceride concentrations are independently associated with subclinical carotid atherosclerosis in women with SLE. Subclinical carotid atherosclerosis is also more prevalent in these women compared with the control group. The study of GCKR rs1260326 gene variants may contribute to more precise assessment of CVR and modulation of the intensity of lipid-lowering treatment in patients with SLE.

Cytokine autoantibodies in SARS-CoV-2 prepandemic and intrapandemic samples from an SLE cohort.

Cytokine autoantibodies, particularly those directed to type I interferon (T1IFN), have been reported to portend an increased risk of severe COVID-19. Since SLE is one of the conditions historically associated with T1IFN autoantibodies, we sought to determine the prevalence of cytokine autoantibodies in our local cohort of 173 patients with SLE prepandemic and intrapandemic, of which nine had confirmed exposure to SARS-CoV-2. Autoantibodies to 16 different cytokines, including T1IFN, were measured by an addressable laser bead immunoassay. None of the 9 patients with confirmed exposure to SARS-CoV-2 had autoantibodies to T1IFN and none had severe COVID-19 symptoms, necessitating hospitalisation. Hence, we could not confirm that TIIFN autoantibodies increase the risk for severe COVID-19. In addition, the cytokine autoantibody pattern did not differ between those with and without evidence of SARS-CoV-2 exposure.

Effect of chronic hydroxychloroquine use on COVID-19 risk in patients with rheumatoid arthritis and systemic lupus erythematosus: a multicenter retrospective cohort.

OBJECTIVE: Hydroxychloroquine (HCQ) has been used during the coronavirus disease 2019 (COVID-19) pandemic because of its reported anti-viral activity. This study examined the association of chronic HCQ use with the incidence and complications of COVID-19. METHODS: This retrospective cohort study included adults with rheumatoid arthritis and/or systemic lupus erythematosus who visited rheumatology clinics in three tertiary hospitals in Riyadh, Saudi Arabia between January 2019 and December 2020. Patients were categorized into two groups based on HCQ use. Data were obtained from the electronic health record and by interviews with patients. The primary study objective was the incidence of COVID-19 and its complications from March 2020 to February 2021. RESULTS: Almost 11% of the study cohort was positive for COVID-19, and the incidence of COVID-19 was similar between HCQ users (11.11%) and nonusers (10.86%). Disease complication rates were similar in the study arms, and they mainly included fever, dry cough, fatigue, and breathing difficulty. CONCLUSIONS: This study revealed no significant association between chronic HCQ use and the incidence of COVID-19, and disease complications were similar in the study arms.

COVID-19 in patients with systemic lupus erythematosus: A systematic review.

The objectives of the study were to review the articles to identify (a) the epidemiology of systemic lupus erythematosus (SLE) and coronavirus disease 2019 (COVID-19); (b) the clinical characteristics of SLE patients with COVID-19; (c) the treatment of COVID-19 in SLE patients; and (d) the impact of COVID-19 pandemic on SLE patients. PubMed was systematically reviewed for literature published from December 2019 to June 2021. Our search was limited to human studies, with language restriction of English. Studies were included if they reported COVID-19 in SLE patients. Our systematic review included 52 studies. The prevalence of COVID-19 infection ranged from 0.0% to 18.1% in SLE patients, and the hospitalisation rates ranged from 0.24% to 10.6%. COVID-19 infection is likely to mimic SLE flare. Hydroxychloroquine (HCQ) was ineffective in prevention of COVID-19, and SLE patients with COVID-19 faced difficulty in healthcare access, had financial constraints and suffered from psychological distress during the pandemic. The pandemic had a significant effect on mental and physical health. Adequate healthcare access, along with containment policies, social distancing measures and psychological nursing was required.

Use of telemedicine for follow-up of lupus nephritis in the COVID-19 outbreak: The 6-month results of a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the short-term patient satisfaction, compliance, disease control, and infection risk of telemedicine (TM) compared with standard in-person follow-up (FU) for patients with lupus nephritis (LN) during the COVID-19 pandemic. METHOD: This was a single-center open-label randomized controlled study. Consecutive patients followed at the LN clinic were randomized to either TM or standard FU (SF) group in a 1:1 ratio. Patients in the TM group received FU via videoconferencing. SF group patients continued conventional in-person outpatient care. The 6-month data were compared and presented. RESULTS: From June to December 2020, 122 patients were randomized (TM: 60, SF: 62) and had at least 2 FUs. There were no baseline differences, including SLEDAI-2k and proportion of patients in lupus low disease activity state (LLDAS), between the two groups except a higher physician global assessment score (PGA) in the TM group. After a mean FU of 19.8 ± 4.5 weeks, the overall patient satisfaction score was higher in the TM group. More patients in the TM group had hospitalization (15/60, 25.0% vs 7/62, 11.3%; p = .049) with higher baseline PGA (OR = 1.17; 95% CI, 1.08-1.26) being the independent predictor. The proportions of patients remained in LLDAS were similar in the two groups (TM: 75.0% vs SF: 74.2%, p = .919). None of the patients had COVID-19. CONCLUSIONS: TM FU resulted in better patient satisfaction and similar short-term disease control in patients with LN compared to standard care. However, it was associated with more hospitalizations and might need to be complemented by in-person visits especially in patients with higher PGA.

Association of COVID-19 pandemic-related concern and health routine changes with functioning among individuals with systemic lupus erythematosus.

OBJECTIVE: To examine whether pandemic-related issues were associated with physical functioning, community mobility and cognition among individuals with SLE. METHODS: Participants were recruited (6 October 2020-11 November 2021) for this cross-sectional study from a population-based cohort of individuals with validated SLE in metropolitan Atlanta, as part of an ongoing ancillary study. Pandemic-related issues (concern about the pandemic (very vs somewhat/not at all concerned); changes in physical activity and sleep (less vs more/same); difficulty obtaining food and medications and accessing routine care (any vs none)) were self-reported. Self-reported physical functioning and episodic and working memory performance were reported as t-scores (such that a score of 50=population mean and a 10-point difference=1 SD) and community mobility scores ranged from 0 to 120, with higher scores representing better functioning for all domains. Differences in scores were assessed via t-tests and age-adjusted, sex-adjusted and race-adjusted linear regression. RESULTS: Among 245 participants (mean age, 46 years; 95% female, 77% black), physical functioning t-scores (mean=44) were consistently lower (by 3-5 points) for those who reported concern about the pandemic, less physical activity and sleep, difficulty obtaining food and medications, and accessing routine care. Similarly, community mobility scores (mean=48) were lower (by 10-20 points) for these individuals. There were no substantial differences in episodic memory and working memory t-scores (mean=50 and 47, respectively) by pandemic-related issues. CONCLUSION: We found that physical functioning and community mobility, but not cognition, were lower among those who reported more concern about the pandemic or greater disruptions to health routines. Future studies should explore interventions among these vulnerable individuals with SLE, who already disproportionately suffer from functional impairment, to maintain functioning and prevent adverse outcomes during times of crisis.