Efficacy and Safety of Anti-SARS-CoV-2 Antiviral Agents and Monoclonal Antibodies in Patients with SLE: A Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19) has spread pandemically with high rates of morbidity and mortality. COVID-19 has also posed unprecedented challenges in terms of rapid development of pharmacological countermeasures to prevent or contrast SARS-CoV-2 pathogenicity. Anti-SARS-CoV-2 antiviral agents and monoclonal antibodies have been specifically designed to attenuate COVID-19 morbidity and prevent mortality in vulnerable subjects, such as patients with immune-mediated diseases, but evidence for the safe and effective use of these drugs in this latter population group is scarce. Therefore, we designed a retrospective, multicentre, observational, case-control study to analyse the impact of these treatments in COVID-19 patients with systemic lupus erythematosus (SLE), a paradigmatic, multi-organ autoimmune disease. We identified 21 subjects treated with antivirals and/or monoclonal antibodies who were matched with 42 untreated patients by age, sex, SLE extension and duration. Treated patients had higher baseline SLE disease activity index 2000 scores [SLEDAI-2K median (interquartile range) = 4 (1-5) vs. 0 (0-2); p = 0.009], higher prednisone doses [5 (0-10) mg vs. 0 (0-3) mg; p = 0.002], and more severe COVID-19 symptoms by a five-point World Health Organisation-endorsed analogue scale [1 (0-1) vs. 0 (0-1); p < 0.010] compared to untreated patients. There was no difference between groups in terms of COVID-19 outcomes and sequelae, nor in terms of post-COVID-19 SLE exacerbations. Three subjects reported mild adverse events (two with monoclonal antibodies, one with nirmatrelvir/ritonavir). These data suggest that anti-SARS-CoV-2 antivirals and monoclonal antibodies might be safely and effectively used in patients with SLE, especially with active disease and more severe COVID-19 symptoms at presentation.

Role of systemic immunosuppression on subglottic stenosis in granulomatosis with polyangiitis: Analysis of a single-centre cohort.

PURPOSE: Subglottic stenosis (SGS) is a potentially life-threatening manifestation of granulomatosis with polyangiitis (GPA). Endoscopic dilation is effective, but relapses are frequent and the benefit of systemic immunosuppression in this setting is still controversial. We aimed to investigate the role of immunosuppressive treatment on SGS relapse risk. METHODS: This is a retrospective observational study based on review of medical charts among our cohort of patients with GPA. RESULTS: Twenty-one patients with SGS-GPA were identified, with a prevalence of 20% among our entire GPA cohort (n = 105). Compared to patients without SGS, patients with SGS-GPA had an earlier disease onset (mean age 30.2 vs. 47.3 years, p<0.001), and lower BVAS (mean 10.5 vs 13.5; p = 0.018). Five patients didn't receive systemic immunosuppression for SGS and they all (100%) relapsed after the first procedure, while among medical treatment group relapse rate was 44% (p = 0.045). When single treatment regimens are considered, rituximab (RTX) and cyclophosphamide (CYC) yielded a protective role towards the need of subsequent dilation procedure after the first if compared with absence of medical treatment. Patients with SGS and generalized disease, who initially received either a RTX- or a CYC-based induction treatment, and higher cumulative doses of glucocorticoids, showed a delayed median time to SGS relapse (36 vs. 12 months, p = 0.024). CONCLUSIONS: Subglottic stenosis is highly prevalent in patients with GPA and may define a milder systemic disease subset occurring more frequently in younger patients. Systemic immunosuppression provides benefit in preventing recurrence of SGS in GPA patients and regimens based on cyclophosphamide or rituximab might have a non-redundant role in this setting.

Post-traumatic stress disorder in patients with systemic lupus erythematosus heavily affects quality of life. A cross-sectional web survey-based study.

OBJECTIVES: Neuropsychiatric symptoms develop in up to 20% of the patients with Systemic Lupus Erythematosus (SLE). Growing evidence is accruing on the association of SLE with Post-traumatic Stress Disorder (PTSD), but little is known about its contribution on patient-reported outcomes. This study focuses on PTSD prevalence in our SLE cohort and on its impact on quality of life. METHODS: Trauma and Loss Spectrum - Self Reported (TALS-SR) and Lupus Quality of Life (Lupus QoL) questionnaires were administered via web to the patients with SLE in our cohort, along with questions on demographical and disease-related aspects. RESULTS: Among 99 patients who completed the questionnaire, fatigue prevalence was 75% and 31% scored TALS-SR test consistently with PTSD. Patients with PTSD achieved lower scores compared to those without PTSD in three Lupus QoL domains: planning (83.3 vs. 100, p = .035), body image (85.0 vs. 95.0, p = .031) and fatigue (66.7 vs. 91.7, p = .001). An inverse correlation was found between TALS-SR domains and Lupus QoL scores, particularly regarding fatigue with reaction to losses or upsetting events (ρ -0.458, p < .001). CONCLUSIONS: PTSD is possibly far more frequent in patients with SLE than in general population and exerts a detrimental influence on quality of life.

A novel evidence-based algorithm to predict thromboembolism in patients with COVID-19: preliminary data from a single-center cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-related disease (COVID-19) is an infectious disease characterized by systemic inflammation, which might enhance baseline thrombotic risk, especially in hospitalized patients. Little is, however, known about predictors of thrombotic complications in patients with COVID-19. METHODS: We prospectively followed up 180 hospitalized COVID-19 patients. Demographics, clinical and laboratory features at presentation and past medical history were tested as predictors of the first thrombotic complication through multivariate Cox regression analysis and a categorical score generated based on the results. RESULTS: Sixty-four thromboses were recorded in 54 patients, of whom seven with thrombosis on admission and 47 with thrombosis during hospitalization. Patients with thrombosis were mainly Caucasian and diabetic, had marked baseline signs of inflammation and organ damage, lower PaO2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages. The latter three variables were independently associated to thrombotic complications and concurred to a 0-5 score, which accounted for 80% of the total sample variability. Patients with three or more points of the newly generated score were at higher risk for thrombotic complications (HR=4.9, P<0.001). Patients with thrombotic complications were more likely to be admitted to intensive care and/or to die (HR=1.9, P=0.036). Five of 180 patients were diagnosed with disseminated intravascular coagulation and three of them died. Eleven minor and no major bleeding events were observed. CONCLUSIONS: Patients with COVID-19 are at increased risk for thrombosis and might be stratified on admission based on lower Pao2/FiO2 ratio, higher D-dimer levels and history of major hemorrhages.

Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19.

PURPOSE: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. METHODS: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. RESULTS: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015). CONCLUSIONS: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.