ObjectiveTo investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.
IntroductionSarcopenia is a chronic condition that is associated with aging and characterized by a reduction of muscle mass, strength, and function. Sarcopenia is prevalent in patients with chronic kidney disease (CKD) and associated with increased morbidity and mortality, as well as cardiovascular complications.ObjectivesTo investigate the prevalence of sarcopenia in patients with CKD not yet on dialysis and its correlation with clinical and laboratory variables and inflammatory markers.MethodsA total of 100 patients of both sexes aged over 18 were evaluated. Sarcopenia was defined using the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP) and of the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project. Sociodemographic and clinical data, activities of daily living, functional capacity, and physical activity were also evaluated. Inflammation was assessed by the serum levels of high-sensitivity C-reactive protein (hsCRP) and interleukin (IL) 4 and 6.ResultsThe prevalence of sarcopenia was 11.9% and 28.7% using the EWGSOP and FNIH criteria, respectively. Sarcopenia was more prevalent in the more advanced stages of CKD (34.5% in stages 2 and 3A; and 65.5% in stages 3B, 4, and 5) and associated with worse performance in activities of daily living (p = 0.049), lower walking speeds (p < 0.001), and higher body mass indexes (BMIs) (p = 0.001) in the non-adjusted model. In addition, patients with sarcopenia had lower functional capacity (p = 0.012) and higher prevalence of physical inactivity (p = 0.041) compared with patients without sarcopenia. After adjustment for confounding variables, sarcopenia was still significantly correlated with walking speed (p = 0.004) and BMI (p = 0.002). HsCRP levels were inversely correlated with appendicular lean mass adjusted for BMI (p = 0.007) and were also positively associated with BMI (p = 0.001). IL4 levels were positively correlated with walking speed (p = 0.007) and lean mass in the lower limbs (p = 0.022).ConclusionsSarcopenia is common in patients with CKD, particularly in the most advanced stages of the disease. We observed an association between the levels of inflammatory markers and peripheral lean body mass, physical performance, and BMI. This association between sarcopenia and modifiable factors highlights the importance of early diagnosis and the implementation of therapeutic measures to minimize adverse outcomes in patients with CKD not yet on dialysis.
Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters—including serum interleukin-6 levels—from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.
ObjectivesTo evaluate risk factors associated with unfavourable outcomes: emergency care, hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death in patients with immune-mediated rheumatic disease (IMRD) and COVID-19.MethodsAnalysis of the first 8 weeks of observational multicentre prospective cohort study (ReumaCoV Brasil register). Patients with IMRD and COVID-19 according to the Ministry of Health criteria were classified as eligible for the study.Results334 participants were enrolled, a majority of them women, with a median age of 45 years; systemic lupus erythematosus (32.9%) was the most frequent IMRD. Emergency care was required in 160 patients, 33.0% were hospitalised, 15.0% were admitted to the ICU and 10.5% underwent mechanical ventilation; 28 patients (8.4%) died. In the multivariate adjustment model for emergency care, diabetes (prevalence ratio, PR 1.38; 95% CI 1.11 to 1.73; p=0.004), kidney disease (PR 1.36; 95% CI 1.05 to 1.77; p=0.020), oral glucocorticoids (GC) (PR 1.49; 95% CI 1.21 to 1.85; p<0.001) and pulse therapy with methylprednisolone (PR 1.38; 95% CI 1.14 to 1.67; p=0.001) remained significant; for hospitalisation, age >50 years (PR 1.89; 95% CI 1.26 to 2.85; p=0.002), no use of tumour necrosis factor inhibitor (TNFi) (PR 2.51;95% CI 1.16 to 5.45; p=0.004) and methylprednisolone pulse therapy (PR 2.50; 95% CI 1.59 to 3.92; p<0.001); for ICU admission, oral GC (PR 2.24; 95% CI 1.36 to 3.71; p<0.001) and pulse therapy with methylprednisolone (PR 1.65; 95% CI 1.00 to 2.68; p<0.043); the two variables associated with death were pulse therapy with methylprednisolone or cyclophosphamide (PR 2.86; 95% CI 1.59 to 5.14; p<0.018).ConclusionsAge >50 years and immunosuppression with GC and cyclophosphamide were associated with unfavourable outcomes of COVID-19. Treatment with TNFi may have been protective, perhaps leading to the COVID-19 inflammatory process.
Sarcopenia is a chronic condition associated with physiological aging process and is defined by the reduction of the mass, muscle strength and function. In Chronic Kidney Disease (CKD), sarcopenia is prevalent and is associated with increased morbidity and mortality and the occurrence of cardiovascular complications. By analyzing sarcopenia in patients with renal insufficiency, complex mechanisms that contribute to loss of muscle mass are highlighted, such as activation of mediators that stimulate the ubiquitin-proteasome system (SUP) ATP-dependent, inflammation, metabolic acidosis, angiotensin II and some hormonal factors. The therapeutic approach to sarcopenia in CKD includes exercises, correction of metabolic acidosis, hormone replacement therapy and insulin resistance. Thus, it is of paramount importance early recognition of sarcopenia in this population, in order to establish effective therapeutic interventions, thus avoiding the full range of complications associated with muscle wasting in CKD.
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