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1.
Clin Exp Rheumatol ; 40(1): 4-14, 2022 01.
Article in English | MEDLINE | ID: covidwho-1856815

ABSTRACT

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.


Subject(s)
Lupus Erythematosus, Systemic , Biomarkers , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy
2.
Clin Exp Rheumatol ; 40(5): 890-896, 2022 May.
Article in English | MEDLINE | ID: covidwho-1780517

ABSTRACT

OBJECTIVES: Antimalarials have been associated with QT prolongation in COVID-19 patients but are generally safe in systemic lupus erythematosus (SLE).We compared the prevalence of QTc prolongation between COVID-19 and SLE patients treated with hydroxychloroquine (HCQ). METHODS: We included patients with SARS-CoV-2 infection confirmed by nasopharyngeal swab and patients taking HCQ for SLE. A prolonged QTc was defined as an increase in QTc intervals >60 ms (compared with baseline) or as a QTc of ≥500 ms. We performed the univariate and multivariate logistic regression to investigate the risk factors for QTc prolongation in COVID-19 patients. RESULTS: We enrolled 58 COVID-19 patients (median age 70.5 years, IQR 25), grouped into group A (patients with HCQ) group B (patients with HCQ + azithromycin) and group C (not received either drug). Fifty (26%) COVID-19 patients presented a QTc prolongation (12 QTc≥500 ms, 3 patients ΔQTc>60 ms). We did not find any differences in QTc prolongation among the three treatment groups. Baseline QTc (OR 111.5) and D-dimer (OR 78.3) were independently associated to QTc prolongation. Compared to the 50 SLE patients (median age 38.5 years, IQR 22), chronically treated with HCQ, COVID-19 patients showed significantly longer QTc (p<0.001). CONCLUSIONS: This is the first study demonstrating that, unlike COVID-19 patients, patients with SLE are not susceptible to HCQ-induced long QT syndrome and arrhythmia. The combined arrhythmogenic effect of SARS-CoV-2 infection and HCQ could account for the excess of QTc prolongation and fatal arrhythmias described in patients with COVID-19.


Subject(s)
COVID-19 , Long QT Syndrome , Lupus Erythematosus, Systemic , Adult , Aged , COVID-19/drug therapy , Case-Control Studies , Electrocardiography , Humans , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Lupus Erythematosus, Systemic/chemically induced , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , SARS-CoV-2
3.
J Int Med Res ; 50(4): 3000605221090363, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1779533

ABSTRACT

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.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Lupus Erythematosus, Systemic , Adult , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , COVID-19/drug therapy , COVID-19/epidemiology , Humans , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Retrospective Studies
4.
Lupus ; 31(6): 684-696, 2022 May.
Article in English | MEDLINE | ID: covidwho-1775183

ABSTRACT

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.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Humans , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Pandemics
5.
Lupus ; 31(2): 221-227, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1649860

ABSTRACT

BACKGROUND: Patients with chronic diseases are potential candidates for inadequate follow-up of drug therapy, tending to incur damage to the intended results. This deserves greater attention in the pandemic period, as they are in the considered risk group. METHODS: We aim to assess Treatment Adherence Measure and analyze associations with characteristics related to the patient, treatment, disease, health professionals and service, and sociodemographic issues in patients with Systemic Lupus Erythematosus (SLE). W conducted a cross-sectional study with a sample of 116 participants, whose data were collected through individual interviews and review of medical records, during the first months of the COVID-19 pandemic in Brazil. Adherence was measured using the Treatment Adherence Measure, and associations were evidenced through described and inferential statistics. RESULTS: The percentage of adherent patients was 55.2%. An association was found between MTA (Medication Treatment Adherence) and physical exercise practice (p = 0.032), and difficulties with treatment (p = 0.002). Conclusion: Participants who did not practice physical exercise were 3.71 times more likely to not adhere to the treatment. Individuals who identified difficulties in the treatment were 3.43 times more likely to not adhere to the treatment; we believe that the pandemic may have influenced this result. More targeted studies are needed to measure the impact on MTA in these patients.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Medication Adherence , Brazil , Cross-Sectional Studies , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Medication Adherence/statistics & numerical data , Pandemics , Pemetrexed
6.
Arthritis Rheumatol ; 74(2): 284-294, 2022 02.
Article in English | MEDLINE | ID: covidwho-1594369

ABSTRACT

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunocompromised Host , Immunogenicity, Vaccine , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , /therapeutic use , Adult , Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Case-Control Studies , Cohort Studies , Enzyme-Linked Immunospot Assay , Female , Glucocorticoids/therapeutic use , Humans , Immunoglobulin G/immunology , Interferon-gamma/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged , Neutralization Tests , Prednisone/therapeutic use , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Symptom Flare Up
7.
Semin Arthritis Rheum ; 52: 151946, 2022 02.
Article in English | MEDLINE | ID: covidwho-1586522

ABSTRACT

BACKGROUND/OBJECTIVES: Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. METHODS: Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. RESULTS: The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p < 0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p < 0.0001), pulmonary hypertension (3.71 [1.84-7.25], p < 0.0002), valvulopathy (6.33 [3.41-11.62], p < 0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p < 0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p = 0.0015). Female sex (0.46 [0.25-0.88], p = 0.0147) and antimalarials (0.28 [0.17-0.45], p < 0.000) proved to be protective factors. CONCLUSIONS: Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.


Subject(s)
Antimalarials , COVID-19 , Heart Failure , Lupus Erythematosus, Systemic , Rheumatology , Antimalarials/therapeutic use , Cross-Sectional Studies , Female , Heart Failure/drug therapy , Heart Failure/epidemiology , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Registries , SARS-CoV-2
8.
RMD Open ; 7(3)2021 12.
Article in English | MEDLINE | ID: covidwho-1551052

ABSTRACT

Since the COVID-19 pandemic, CoronaVac, an inactivated SARS-CoV-2 vaccine, has been widely deployed in several countries for emergency use. However, the immunogenicity of the inactivated vaccine was relatively lower when compared to other vaccine types and was even more attenuated in autoimmune patients with rheumatic disease. A third-dose SARS-CoV-2 vaccination in immunosuppressed population is recommended in order to improve immune response. However, the data were limited to those initially received mRNA or viral vector SARS-CoV-2 vaccine. Thus, we aimed to describe the safety, reactogenicity and immunogenicity of patients with systemic lupus erythematosus (SLE) who received a heterogenous booster SARS-CoV-2 vaccine following the initial CoronaVac inactivated vaccine series. Our findings support that the third booster dose of mRNA or viral vector vaccine following the inactivated vaccine is well tolerated and elicited a substantial humoral and cellular immune response in inactive patients with SLE having maintenance immunosuppressive therapy without interruption of immunosuppressive medications.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Lupus Erythematosus, Systemic/drug therapy , Pandemics , SARS-CoV-2
9.
Int Immunopharmacol ; 101(Pt B): 108254, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1549846

ABSTRACT

With the outbreak and rapid spread of COVID-19, the world health situation is unprecedentedly severe. Systemic lupus erythematosus (SLE) is a common autoimmune disease, which can cause multiple organ damage. Numerous studies have shown that immune factors have important roles in the pathogenesis of both COVID-19 and SLE. In the early stages of COVID-19 and SLE pathogenesis, IFN-α expression is frequently increased, which aggravates the virus infection and promotes SLE development. In addition, increased IL-6 levels, caused by different mechanisms, are observed in the peripheral blood of patients with severe COVID-19 and SLE, stimulating a series of immune cascades that lead to a cytokine storm, as well as causing B cell hyperfunction and production of numerous of antibodies, aggravating both COVID-19 and SLE. In this review, we explore the background immunopathological mechanisms in COVID-19 and SLE and analyze the advantages and disadvantages of commonly used SLE drugs for patients with COVID-19, to optimize treatment plans for patients with SLE who develop COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/immunology , Interferon-alpha/immunology , Interleukin-6/immunology , Lupus Erythematosus, Systemic/immunology , SARS-CoV-2 , Animals , Humans , Lupus Erythematosus, Systemic/drug therapy
10.
Pediatr Rheumatol Online J ; 19(1): 162, 2021 Nov 27.
Article in English | MEDLINE | ID: covidwho-1538079

ABSTRACT

BACKGROUND: This study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death. METHODS: An observational longitudinal study was conducted during the first year of the SARS-CoV-2 pandemic (March 2020-March 2021). All pediatric patients attended at the rheumatology outpatient clinics of six tertiary referral hospitals in Madrid, Spain, with a diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic and clinical characteristics and treatment regimens. We ran a multivariable logistic regression model to assess associated factors for outcomes. RESULTS: The study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients (38.96%) were asymptomatic, 41 (53.25%) had a mild-moderate COVID-19 and 6 patients (7.79%) required hospital admission. The median length of hospital admission was 5 (2-20) days, one patient required intensive care and there were no deaths. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was previous use of glucocorticoids (OR 3.51; p = 0.00). No statistically significant risk factors for symptomatic COVID-19 were found in the final model. CONCLUSION: No differences in COVID-19 outcomes according to childhood-onset rheumatic disease types were found. Results suggest that associated comorbidities and treatment with glucocorticoids increase the risk of hospital admission.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19/physiopathology , Glucocorticoids/therapeutic use , Hospitalization/statistics & numerical data , Rheumatic Diseases/drug therapy , Adolescent , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/epidemiology , Asthma/epidemiology , COVID-19/epidemiology , Carrier State/epidemiology , Child , Cohort Studies , Comorbidity , Female , Heart Diseases/epidemiology , Hereditary Autoinflammatory Diseases/drug therapy , Hereditary Autoinflammatory Diseases/epidemiology , Humans , Intensive Care Units, Pediatric , Length of Stay , Logistic Models , Longitudinal Studies , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Male , Multivariate Analysis , Obesity/epidemiology , Renal Insufficiency, Chronic/epidemiology , Rheumatic Diseases/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology
11.
RMD Open ; 7(3)2021 11.
Article in English | MEDLINE | ID: covidwho-1504941

ABSTRACT

OBJECTIVES: To compare current all-cause mortality rates in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) versus general population. METHODS: In this population-based, retrospective cohort study, anonymised data on 11 186 586 citizens, including all patients with RA (42 735, 79% female), AS (9707, 43% female), PsA (13 779, 55% female), SLE (10 440, 89% female) and SSc (2277, 88% female), (median age of 64/47/54/53/59 years at study entry, respectively), under prescribed treatment between 2015 and 2019, were extracted from the electronic database covering nearly 99% of the Greek population. RESULTS: After 1:5 (patients:general population) matching for gender/age, we found that survival was worse in SSc, followed by SLE and inflammatory arthritis. Compared with the general population HRs for death increased from the first 3 years to 5 years of observation possibly due to increases in disease duration: RA (from 0.63 to 1.13 (95% CI: 1.05 to 1.22), AS (from 0.62 to 1.01, (95% CI: 0.76 to 1.33)), PsA (from 0.68 to 1.06, (95% CI: 0.88 to 1.28)), SLE (from 1.52 to 1.98, (95% CI: 1.67 to 2.33)) and SSc (from 2.27 to 4.24, (95% CI: 3.19 to 5.63)). In both SLE and SSc mortality was increased in men than women and in patients younger than 50 years. CONCLUSIONS: Survival rates over 5 years in inflammatory arthritis under treatment are currently becoming comparable (AS/PsA) or slightly higher (RA) than those of the general population. However, all-cause mortality is almost twofold and fourfold higher in SLE and SSc, respectively, being even higher for male and younger patients.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Lupus Erythematosus, Systemic , Rheumatic Diseases , Arthritis, Psoriatic/drug therapy , Female , Humans , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , Retrospective Studies , Rheumatic Diseases/drug therapy
12.
Biomolecules ; 11(11)2021 11 03.
Article in English | MEDLINE | ID: covidwho-1502359

ABSTRACT

Immune cells, including dendritic cells, macrophages, and T and B cells, express the vitamin D receptor and 1α-hydroxylase. In vitro studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, has an anti-inflammatory effect. Recent epidemiological evidence has indicated a significant association between vitamin D deficiency and an increased incidence, or aggravation, of infectious diseases and inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. However, the impact of vitamin D on treatment and prevention, particularly in infectious diseases such as the 2019 coronavirus disease (COVID-19), remains controversial. Here, we review recent evidence associated with the relationship between vitamin D and inflammatory diseases and describe the underlying immunomodulatory effect of vitamin D.


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , Immune System/drug effects , Inflammation/drug therapy , Vitamin D/therapeutic use , Animals , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/prevention & control , Autoimmune Diseases/drug therapy , B-Lymphocytes/immunology , Dendritic Cells/immunology , Disease Models, Animal , Humans , Influenza, Human/drug therapy , Influenza, Human/prevention & control , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/prevention & control , Macrophages/immunology , Mice , Monocytes/immunology , Multiple Sclerosis/drug therapy , Multiple Sclerosis/prevention & control , Receptors, Calcitriol/genetics , Receptors, Calcitriol/physiology , T-Lymphocytes/immunology , Vitamin D Deficiency/complications
13.
Autoimmun Rev ; 20(12): 102984, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1491721

ABSTRACT

The mechanistic target of rapamycin (mTOR) pathway integrates metabolic cues into cell fate decisions. A particularly fateful event during the adaptive immune response is the engagement of a T cell receptor by its cognate antigen presented by an antigen-presenting cell (APC). Here, the induction of adequate T cell activation and lineage specification is critical to mount protective immunity; at the same time, inadequate activation, which could lead to autoimmunity, must be avoided. mTOR forms highly conserved protein complexes 1 and 2 that shape lineage specification by integrating signals originating from TCR engagement, co-stimulatory or co-inhibitory receptors and cytokines and availability of nutrients. If one considers autoimmunity as the result of aberrant lineage specification in response to such signals, the importance of this pathway becomes evident; this provides the conceptual basis for mTOR inhibition in the treatment of systemic autoimmunity, such as systemic lupus erythematosus (SLE). Clinical trials in SLE patients have provided preliminary evidence that mTOR blockade by sirolimus (rapamycin) can reverse pro-inflammatory lineage skewing, including the expansion of Th17 and double-negative T cells and plasma cells and the contraction of regulatory T cells. Moreover, sirolimus has shown promising efficacy in the treatment of refractory idiopathic multicentric Castleman disease, newly characterized by systemic autoimmunity due to mTOR overactivation. Alternatively, mTOR blockade enhances responsiveness to vaccination and reduces infections by influenza virus in healthy elderly subjects. Such seemingly contradictory findings highlight the importance to further evaluate the clinical effects of mTOR manipulation, including its potential role in treatment of COVID-19 infection. mTOR blockade may extend healthy lifespan by abrogating inflammation induced by viral infections and autoimmunity. This review provides a mechanistic assessment of mTOR pathway activation in lineage specification within the adaptive and innate immune systems and its role in health and autoimmunity. We then discuss some of the recent experimental and clinical discoveries implicating mTOR in viral pathogensis and aging.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Aged , Antiviral Agents/therapeutic use , Autoimmunity , Humans , Longevity , Lupus Erythematosus, Systemic/drug therapy , SARS-CoV-2 , TOR Serine-Threonine Kinases/therapeutic use
14.
Int J Hematol ; 115(3): 424-427, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1482297

ABSTRACT

Evans syndrome presents as concurrent autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Systemic lupus erythematosus (SLE) is the most frequent autoimmune disorder associated with Evans syndrome. We herein report a case of new-onset Evans syndrome associated with SLE after BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccination in a 53-year-old woman. Blood examination at diagnosis showed hemolytic anemia with a positive Coombs test and thrombocytopenia. Hypocomplementemia and the presence of lupus anticoagulant indicated a strong association with SLE. Prednisolone administration rapidly restored hemoglobin level and platelet count. This case suggests that mRNA COVID-19 vaccination may cause an autoimmune disorder. Physicians should be aware of this adverse reaction by mRNA COVID-19 vaccination and should consider the benefits and risks of vaccination for each recipient.


Subject(s)
Anemia, Hemolytic, Autoimmune/etiology , Lupus Erythematosus, Systemic/etiology , Thrombocytopenia/etiology , Vaccination/adverse effects , Anemia, Hemolytic, Autoimmune/diagnosis , Anemia, Hemolytic, Autoimmune/drug therapy , Female , Hematologic Tests/methods , Hemoglobins , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Middle Aged , Platelet Count , Prednisolone/administration & dosage , Purpura, Thrombocytopenic, Idiopathic , Risk Assessment , Thrombocytopenia/diagnosis , Thrombocytopenia/drug therapy
15.
Ann Rheum Dis ; 81(4): 575-583, 2022 04.
Article in English | MEDLINE | ID: covidwho-1450597

ABSTRACT

OBJECTIVES: Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination. METHODS: In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine until day 15 after the second dose in 126 patients with SLE. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T cell responses were quantified by interferon-γ release assay after the second dose. RESULTS: BNT162b2 was well tolerated and no statistically significant variations of BILAG (British Isles Lupus Assessment Group) and SLEDAI (SLE Disease Activity Index) scores were observed throughout the study in patients with SLE with active and inactive disease at baseline. Mycophenolate mofetil (MMF) and methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody response (ß=-78, p=0.007; ß=-122, p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total immunoglobulin G serum levels, naïve B cell frequencies (ß=2, p=0.018; ß=2.5, p=0.003) and SARS-CoV-2-specific T cell response (r=0.462, p=0.003). In responders, serum neutralisation activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients. CONCLUSION: MMF, MTX and poor baseline humoral immune status, particularly low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating patients with SLE who might need adapted vaccine regimens and follow-up.


Subject(s)
Antirheumatic Agents/adverse effects , Immunity, Humoral/drug effects , Lupus Erythematosus, Systemic/immunology , SARS-CoV-2/immunology , Adult , Antibodies, Viral/immunology , Antirheumatic Agents/immunology , COVID-19/prevention & control , Female , Humans , Immunogenicity, Vaccine/drug effects , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/virology , Male , Methotrexate/adverse effects , Methotrexate/immunology , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/immunology , Prospective Studies , Severity of Illness Index
16.
Front Immunol ; 12: 724047, 2021.
Article in English | MEDLINE | ID: covidwho-1405412

ABSTRACT

Objectives: Impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on individuals with arthritis has been highlighted whereas data on other rheumatic diseases, e.g., systemic lupus erythematosus (SLE), are scarce. Similarly to SLE, severe SARS-CoV-2 infection includes risks for thromboembolism, an unbalanced type I interferon response, and complement activation. Herein, SARS-CoV-2 antibodies in longitudinal samples collected prior to vaccination were analyzed and compared with SLE progression and antinuclear antibody (ANA) levels. Methods: One hundred patients (83 women) with established SLE and a regular visit to the rheumatologist (March 2020 to January 2021) were included. All subjects donated blood and had done likewise prior to the pandemic. SARS-CoV-2 antibody isotypes (IgG, IgA, IgM) to the cell receptor-binding S1-spike outer envelope protein were detected by ELISA, and their neutralizing capacity was investigated. IgG-ANA were measured by multiplex technology. Results: During the pandemic, 4% had PCR-confirmed infection but 36% showed SARS-CoV-2 antibodies of ≥1 isotype; IgA was the most common (30%), followed by IgM (9%) and IgG (8%). The antibodies had low neutralizing capacity and were detected also in prepandemic samples. Plasma albumin (p = 0.04) and anti-dsDNA (p = 0.003) levels were lower in patients with SARS-CoV-2 antibodies. Blood group, BMI, smoking habits, complement proteins, daily glucocorticoid dose, use of hydroxychloroquine, or self-reported coronavirus disease 2019 (COVID-19) symptoms (except fever, >38.5°C) did not associate with SARS-CoV-2 antibodies. Conclusion: Our data from early 2021 indicate that a large proportion of Swedish SLE patients had serological signs of exposure to SARS-CoV-2 but apparently with a minor impact on the SLE course. Use of steroids and hydroxychloroquine showed no distinct effects, and self-reported COVID-19-related symptoms correlated poorly with all antibody isotypes.


Subject(s)
Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/immunology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Antibodies, Viral/blood , Female , Humans , Immunoglobulin Isotypes/blood , Immunoglobulin Isotypes/immunology , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , SARS-CoV-2
17.
J Med Virol ; 93(2): 755-759, 2021 02.
Article in English | MEDLINE | ID: covidwho-1384219

ABSTRACT

Hydroxychloroquine sulfate (HCQ) is being scrutinized for repositioning in the treatment and prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This antimalarial drug is also chronically used to treat patients with autoimmune diseases. By analyzing the Portuguese anonymized data on private and public based medical prescriptions we have identified all cases chronically receiving HCQ for the management of diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and other autoimmune diseases. Additionally, we have detected all laboratory confirmed cases of SARS-CoV-2 infection and all laboratory confirmed negative cases in the Portuguese population (mandatorily registered in a centrally managed database). Cross linking the two sets of data has allowed us to compare the proportion of HCQ chronic treatment (at least 2 grams per month) in laboratory confirmed cases of SARS-CoV-2 infection with laboratory confirmed negative cases. Out of 26 815 SARS-CoV-2 positive patients, 77 (0.29%) were chronically treated with HCQ, while 1215 (0.36%) out of 333 489 negative patients were receiving it chronically (P = .04). After adjustment for age, sex, and chronic treatment with corticosteroids and/or immunosuppressants, the odds ratio of SARS-CoV-2 infection for chronic treatment with HCQ has been 0.51 (0.37-0.70). Our data suggest that chronic treatment with HCQ confer protection against SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Pre-Exposure Prophylaxis , Adult , Aged , Antimalarials/therapeutic use , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , COVID-19/immunology , COVID-19/virology , Drug Administration Schedule , Drug Repositioning , Female , Humans , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Odds Ratio , Portugal , Registries , Retrospective Studies , SARS-CoV-2/drug effects , SARS-CoV-2/immunology
18.
Clin Immunol ; 231: 108845, 2021 10.
Article in English | MEDLINE | ID: covidwho-1377685

ABSTRACT

Little is known about the impact of coronavirus disease 2019 (COVID-19) pandemic to the care of patients with systemic lupus erythematosus (SLE) in the long-term. By crossing population data with the results of a web-based survey focused on the timeframes January-April and May-December 2020, we found that among 334/518 responders, 28 had COVID-19 in 2020. Seventeen cases occurred in May-December, in parallel with trends in the general population and loosening of containment policy strength. Age > 40 years (p = 0.026), prednisone escalation (p = 0.008) and infected relatives (p < 0.001) were most significantly associated with COVID-19. Weaker associations were found with asthma, lymphadenopathy and azathioprine or cyclosporine treatment. Only 31% of patients with infected relatives developed COVID-19. Healthcare service disruptions were not associated with rising hospitalisations. Vaccination prospects were generally welcomed. Our data suggest that COVID-19 has a moderate impact on patients with SLE, which might be significantly modulated by public health policies, including vaccination.


Subject(s)
COVID-19/complications , Lupus Erythematosus, Systemic/complications , SARS-CoV-2 , Adolescent , Adult , Aging , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Vaccines/immunology , Data Collection , Female , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Lupus Erythematosus, Systemic/drug therapy , Male , Middle Aged , Surveys and Questionnaires , Vaccination Refusal , Young Adult
19.
BMJ Case Rep ; 14(8)2021 Aug 25.
Article in English | MEDLINE | ID: covidwho-1373953

ABSTRACT

A 39-year-old woman with systemic lupus erythematosus treated with anti-CD20 monoclonal antibody rituximab was admitted to our hospital with COVID-19 pneumonia. Despite receiving dexamethasone, she developed hypoxaemia and persistent lung opacities. As bronchoalveolar lavage was suggestive of cryptogenic organising pneumonia, high-dose corticosteroid was administered, and she received antimicrobial therapy for opportunistic infections without improvement. Reverse transcription PCR was repeatedly positive for SARS-CoV-2, and virus replication was confirmed in cell cultures. As no anti-SARS-CoV-2 antibodies were detected more than 100 days after symptom onset, she was treated with convalescent plasma with fast clinical improvement, returning home days later. Our case shows that persistent SARS-CoV-2 infection in an immunocompromised patient may be overturned with the appropriate treatment.


Subject(s)
COVID-19 , Lupus Erythematosus, Systemic , Adult , COVID-19/therapy , Female , Humans , Immunization, Passive , Immunocompromised Host , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , SARS-CoV-2
20.
Pharmacol Res Perspect ; 9(5): e00842, 2021 10.
Article in English | MEDLINE | ID: covidwho-1366267

ABSTRACT

This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll-like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double-blind, placebo-controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single-dose cohorts received one dose of enpatoran (1, 3, 9, 25, 50, 100, or 200 mg) or placebo using a sentinel dosing strategy. Multiple-dose cohorts received enpatoran (9, 25, or 200 mg once daily, or 25 or 50 mg twice daily) or placebo for 14 days. Safety, tolerability, PK, and PD (ex vivo-stimulated cytokine secretion) were assessed in both parts. The effect of food was assessed in an open-label, one-way crossover study in the 25 mg single-dose cohort. Single- and multiple-oral doses of enpatoran up to 200 mg were well tolerated and no significant dose-limiting adverse events or safety signals were observed under fasting or fed conditions. PK parameters were linear and dose-proportional across the dose range evaluated, with a slightly delayed absorption and lower peak concentration observed at 25 mg with food. Exposure-dependent inhibition of ex vivo-stimulated interleukin-6 secretion was observed, with maximum inhibition at 200 mg. Enpatoran was well tolerated at doses up to 200 mg. Further investigation of enpatoran is warranted as a potential treatment for diseases driven by TLR7/8 overactivation, such as systemic lupus erythematosus and COVID-19 pneumonia.


Subject(s)
Immunologic Factors/pharmacology , Toll-Like Receptor 7/antagonists & inhibitors , Toll-Like Receptor 8/antagonists & inhibitors , Administration, Oral , Adult , COVID-19/drug therapy , COVID-19/immunology , Double-Blind Method , Female , Humans , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/immunology , Male , SARS-CoV-2
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