Project description:The pathophysiologic significance of redox imbalance is unquestionable as numerous reports and topic reviews indicate alterations in redox parameters during corona virus disease 2019 (COVID-19). However, a more comprehensive understanding of redox-related parameters in the context of COVID-19-mediated inflammation and pathophysiology is required. COVID-19 subjects (n=64) and control subjects (n=19) were enrolled, and blood was drawn within 72 hours of diagnosis. Serum multiplex assay and buffy coat cell mRNA sequencing was performed. Oxidant/free radical (electron paramagnetic resonance (EPR) spectroscopy, nitrite-nitrate assay) and antioxidant (ferrous reducing ability of serum assay and high-performance liquid chromatography) were performed. Multivariate analyses were performed to evaluate potential of indicated parameters to predict clinical outcome. Significantly greater levels of multiple inflammatory and vascular markers were quantified in the subjects admitted to the ICU compared to non-ICU subjects. Gene set enrichment analyses indicated significant enhancement of oxidant related pathways and biochemical assays confirmed a significant increase in free radical production and uric acid reduction in COVID-19 subjects. Multivariate analyses confirmed a positive association between serum levels of VCAM-1, ICAM-1 and a negative association between the abundance of one electron oxidants (detected by ascorbate radical formation) and mortality in COVID subjects while IL-17c and TSLP levels predicted need for intensive care in COVID-19 subjects.
Project description:Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established.Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population.Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non-idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death.Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17-2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39-3.71).Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
Project description:IntroductionThe COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD).Methods and analysisThe UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment.Ethics and disseminationAll contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals.ConclusionThis study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
Project description:ImportanceHealth care systems have implemented remote patient monitoring (RPM) programs to manage patients with COVID-19 at home, but the associations between participation and outcomes or resource utilization are unclear.ObjectiveTo assess whether an RPM program for COVID-19 is associated with lower or higher likelihood of hospitalization and whether patients who are admitted present earlier or later for hospital care.Design, setting, and participantsThis retrospective, observational, cohort study of RPM was performed at Froedtert & Medical College of Wisconsin Health Network, an academic health system in southeastern Wisconsin. Participants included patients with internal primary care physicians and a positive SARS-CoV-2 test in the ambulatory setting between March 30, 2020, and December 15, 2020. Data analysis was performed from February 15, 2021, to February 2, 2022.ExposuresActivation of RPM program.Main outcomes and measuresHospitalizations within 2 to 14 days of a positive test. Inverse propensity score weighting was used to account for differences between groups. Sensitivity analyses were performed looking at usage of the RPM among patients who activated the program.ResultsA total of 10 660 COVID-19-positive ambulatory patients were eligible, and 9378 (88.0%) had email or mobile numbers on file and were invited into the RPM program; the mean (SD) age was 46.9 (16.3) years and 5448 patients (58.1%) were women. Patients who activated monitoring (5364 patients [57.2%]) had a mean (SD) of 35.3 (33.0) check-ins and a mean (SD) of 1.27 (2.79) (median [IQR], 0 [0-1]) free-text comments. A total of 878 patients (16.4%) experienced at least 1 alert; 128 of 5364 activated patients (2.4%) and 158 of 4014 inactivated patients (3.9%) were hospitalized (χ21 = 18.65; P < .001). In weighted regression analysis, activation of RPM was associated with a lower odds of hospitalization (odds ratio, 0.68; 95% CI, 0.54-0.86; P = .001) adjusted for demographics, comorbidities, and time period. Monitored patients had a longer mean (SD) time between test and hospitalization (6.67 [3.21] days vs 5.24 [3.03] days), a shorter length of stay (4.44 [4.43] days vs 7.14 [8.63] days), and less intensive care use (15 patients [0.3%] vs 44 patients [1.1%]).Conclusions and relevanceThese findings suggest that activation of an RPM program is associated with lower hospitalization, intensive care use, and length of stay among patients with COVID-19.
Project description:BackgroundPatients hospitalized with COVID-19 have an increased incidence of thromboembolism. The role of extended thromboprophylaxis after hospital discharge is unclear.ObjectiveTo determine whether anticoagulation is superior to placebo in reducing death and thromboembolic complications among patients discharged after COVID-19 hospitalization.DesignProspective, randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT04650087).SettingDone during 2021 to 2022 among 127 U.S. hospitals.ParticipantsAdults aged 18 years or older hospitalized with COVID-19 for 48 hours or more and ready for discharge, excluding those with a requirement for, or contraindication to, anticoagulation.Intervention2.5 mg of apixaban versus placebo twice daily for 30 days.MeasurementsThe primary efficacy end point was a 30-day composite of death, arterial thromboembolism, and venous thromboembolism. The primary safety end points were 30-day major bleeding and clinically relevant nonmajor bleeding.ResultsEnrollment was terminated early, after 1217 participants were randomly assigned, because of a lower than anticipated event rate and a declining rate of COVID-19 hospitalizations. Median age was 54 years, 50.4% were women, 26.5% were Black, and 16.7% were Hispanic; 30.7% had a World Health Organization severity score of 5 or greater, and 11.0% had an International Medical Prevention Registry on Venous Thromboembolism risk prediction score of greater than 4. Incidence of the primary end point was 2.13% (95% CI, 1.14 to 3.62) in the apixaban group and 2.31% (CI, 1.27 to 3.84) in the placebo group. Major bleeding occurred in 2 (0.4%) and 1 (0.2%) and clinically relevant nonmajor bleeding occurred in 3 (0.6%) and 6 (1.1%) apixaban-treated and placebo-treated participants, respectively. By day 30, thirty-six (3.0%) participants were lost to follow-up, and 8.5% of apixaban and 11.9% of placebo participants permanently discontinued the study drug treatment.LimitationsThe introduction of SARS-CoV-2 vaccines decreased the risk for hospitalization and death. Study enrollment spanned the peaks of the Delta and Omicron variants in the United States, which influenced illness severity.ConclusionThe incidence of death or thromboembolism was low in this cohort of patients discharged after hospitalization with COVID-19. Because of early enrollment termination, the results were imprecise and the study was inconclusive.Primary funding sourceNational Institutes of Health.