Project description:Aim: To investigate clinical implications of antineutrophil cytoplasmic antibody (ANCA) positivity detected in COVID-19 patients during follow up. Materials and methods: A retrospective survey in a hospital database was carried out to detect COVID-19 patients in which ANCAs had been tested. Clinical, laboratory and imaging data were collected from this hospital database and compared between ANCA-negative and -positive patients. Results: ANCAs were tested in 87 COVID-19 patients. Eight had positivity in at least one ANCA test. COVID-19 symptoms on admission and rate of pulmonary involvement were similar. Acute phase reactant levels were higher in ANCA-positive patients. Rate of mortality was higher in the ANCA-positive group without statistical significance. Conclusion: ANCA positivity detected during COVID-19 in patients without a prior diagnosis of any rheumatic condition may be related with worse outcomes.
Project description:Renalase is a secreted flavoprotein with anti-inflammatory and pro-cell survival properties. COVID-19 is associated with disordered inflammation and apoptosis. We hypothesized that blood renalase levels would correspond to severe COVID-19 and survival. In this retrospective cohort study, clinicopathologic data and blood samples were collected from hospitalized COVID-19 subjects (March-June 2020) at a single institution tertiary hospital. Plasma renalase and cytokine levels were measured and clinical data abstracted from health records. Of 3,450 COVID-19 patients, 458 patients were enrolled. Patients were excluded if <18 years, or opted out of research. The primary composite outcome was intubation or death within 180 days. Secondary outcomes included mortality alone, intensive care unit admission, use of vasopressors, and CPR. Enrolled patients had mean age 64 years (SD±17), were 53% males, and 48% non-whites. Mean renalase levels was 14,108·4 ng/ml (SD±8,137 ng/ml). Compared to patients with high renalase, those with low renalase (< 8,922 ng/ml) were more likely to present with hypoxia, increased ICU admission (54% vs. 33%, p < 0.001), and cardiopulmonary resuscitation (10% vs. 4%, p = 0·023). In Cox proportional hazard model, every 1000 ng/ml increase in renalase decreased the risk of death or intubation by 5% (HR 0·95; 95% CI 0·91-0·98) and increased survival alone by 6% (HR 0·95; CI 0·90-0·98), after adjusting for socio-demographics, initial disease severity, comorbidities and inflammation. Patients with high renalase-low IL-6 levels had the best survival compared to other groups (p = 0·04). Renalase was independently associated with reduced intubation and mortality in hospitalized COVID-19 patients. Future studies should assess the pathophysiological relevance of renalase in COVID-19 disease.
Project description:The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. For the first time, our study provides the unique advantage of obtaining samples from the Middle Eastern population, an underrepresented region in genetic studies, and explore new genotypes in this population that will yield to novel genetic association. Specifically, we studied 646 patients in the United Arab Emirates. We describe strong association signals from genes on chromosomes 2, 3, 5, 11 and 13, which carry genes that are expressed in the lung, have been associated with tumour progression, emphysema, airway obstruction, and surface tension within the lung. Identifying genetic variants associated to COVID-19 susceptibility and severity may uncover novel biological insights into disease pathogenesis and identify mechanistic targets for therapeutic and vaccine development.
Project description:ObjectiveTo assess the association of depression and anxiety with clinical outcomes and laboratory markers among hospitalized patients with coronavirus disease 2019 (COVID-19).MethodsA prospective cohort study in Wuhan, China was conducted in 205 adult hospitalized patients with a diagnosis of moderate coronavirus disease from admission through discharge or death. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). The primary outcome was the incidence of severe or critical COVID-19, and the secondary outcomes were increased length of hospital stay and altered laboratory markers during follow up.ResultsAmong the 205 hospitalized patients (mean age 58 years; 51.7% male), 25 (12.2%) developed severe or critical COVID-19. According to the HADS scores, 51 (24.9%) and 92 (44.9%) of participants presented with clinically significant anxiety and depression, respectively. Using multi-variable adjusted Cox regression analysis, the adjusted hazard ratio of developing severe or critical COVID-19 associated with anxiety and depression was 1.55 (95% CI: 0.63, 3.80) and 4.28 (95% CI: 1.20, 15.30), respectively. The risk of developing severe or critical COVID-19 with both anxiety and depression was more than four times higher than in patients without anxiety or depression (HR, 4.05; 95% CI: 1.02, 16.00). In addition, both the trends of depression and anxiety were positively associated with a prolonged duration of hospitalization, and immune response was significantly decreased in patients with depression than those without.ConclusionsIn patients having coronavirus disease, depression was associated with worse clinical outcomes. These findings highlight the importance of prevention and management of mental health problems in confronting the COVID-19 pandemic.
Project description:Purpose: To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China.Methods: This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR).Results: Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008).Conclusion: Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement.
Project description:ObjectiveTo investigate serum IL-6 (sIL-6) levels during active disease, complete remission (CR), and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with clinical outcomes.MethodssIL-6 levels were measured at baseline and longitudinally over 18 months, in 78 patients with AAV enrolled in a randomized controlled trial comparing treatment with either rituximab (RTX) or cyclophosphamide (CYC)/azathioprine (AZA). Outcome variables included baseline clinical features, ANCA specificity, disease activity (active disease versus CR), time to relapse events, B cell repopulation, and ANCA titer increases.ResultsAt baseline, sIL6 levels were detectable in 81% of patients; 73% (n = 57) of subjects were proteinase 3 (PR3)-ANCA positive, sIL-6 levels were higher in subjects with PR3-ANCAs and positively correlated with their levels (rs = 0.36,p < 0.01), but not with levels of myeloperoxidase (MPO)-ANCA (rs = -0.17,p = 0.47). Higher baseline sIL-6 levels were associated with PR3-ANCA positivity, fever, pulmonary nodules/cavities, conductive deafness, and absence of urinary red blood cell casts (p < 0.05). Baseline sIL6 levels did not predict CR at month 6 (p = 0.71), and the median sIL-6 level declined from baseline with induction therapy, regardless of CR achievement. An increase in sIL-6 during CR was a predictor for subsequent severe relapse in RTX-treated patients (hazard ratio (HR):7.24,p = 0.01), but not in CYC/AZA-treated patients (HR:0.62,p = 0.50). In contrast, a sIL-6 increase did not predict B cell repopulation or ANCA titer increase in either treatment arm (p > 0.05).ConclusionAt baseline, sIL-6 concentrations correlate with PR3-ANCA titers and are associated with specific clinical manifestations of AAV. Baseline sIL6 concentrations do not predict CR at 6 months, but the increase in sIL-6 concentrations during CR is associated with subsequent severe relapse among RTX-treated patients. Further investigation into the mechanistic role of IL6 in AAV might lead to identifying this pathway as a potential therapeutic target in this disease.
Project description:Coronavirus disease 2019 (COVID-19) can be asymptomatic or lead to a wide spectrum of symptoms, ranging from mild upper respiratory system involvement to acute respiratory distress syndrome, multi-organ damage and death. In this study, we explored the potential of microRNAs (miRNA) in delineating patient condition and in predicting clinical outcome. Analysis of the circulating miRNA profile of COVID-19 patients, sampled at different hospitalization intervals after admission, allowed to identify miR-144-3p as a dynamically regulated miRNA in response to COVID-19.