POS-906 TREATMENT WITH RECOMBINANT MUTATED HUMAN ANGIOPOIETIN-LIKE 4 AMELIORATES GLOMERULAR INJURY IN A MODEL OF THE COVID-19 CYTOKINE STORM

Introduction: Some patients with COVID-19 infection develop proteinuria or Acute Kidney Injury, and cases of COVID-19 related Collapsing Glomerulopathy have also been reported. Three published human kidney biopsy studies did not find viral particles in the glomeruli or tubules. This raises the possibility of glomerular and kidney injury induced by the extensive cytokine storm documented early on in the pandemic in hospitalized COVID-19 patients. Mutated forms of Human Angiopoietin-like 4 (protein 8520) were previously shown to reduce proteinuria in rat models of FSGS and diabetic nephropathy (Clement LC, Mace C et al. Nature Medicine 2014). Using different components or innate and adaptive immunity triggered during infection, we developed cytokine cocktails that mimic the COVID-19 cytokine storm, and tested the ability of protein 8520 to reduce glomerular injury in this model. Methods: After baseline urine and blood collections, two groups of BALB/c mice (mean n = 5 mice per group) were injected intravenously with dose 1.8 X of COVID Cocktail D. One hour later, they received 10 μg of His-Tag purified protein 8520 or control human albumin. Overall activity status was documented at 6 and 24 hours. At 24 hours after model induction, blood and urine samples were collected, and the mice euthanized, followed by harvesting of multiple organs including kidneys. Urine albumin was measured by ELISA (Bethyl Labs), and urine and serum creatinine by Mass Spectrometry. Results: Baseline urine albumin to creatinine ratio was similar between the two groups. At 24 hours, urine albumin to creatinine ratio was significantly lower in the 8520 treated compared to control treated group (P < 0.05). Serum creatinine on Day 1 was similar between both groups, and not significantly elevated compared to baseline. Kidney sections were processed for light and electron microscopy, and analysis of these studies is in progress. Conclusions: Treatment with recombinant mutated human Angiopoietin-like 4 reduces albuminuria in a mouse model of the COVID-19 cytokine storm. Further studies will be conducted to establish a potential therapeutic role in viral cytokine storms. No conflict of interest

Changes in Care during the COVID-19 Pandemic for People with Cystic Fibrosis.

Rationale: Cystic fibrosis (CF) centers transitioned to telemedicine during the spring 2020 peak of the coronavirus disease (COVID-19) pandemic. Objectives: We hypothesized that people with CF (pwCF) with more severe disease would be more likely to be seen in-person. Methods: We used paired t tests to compare within-subject changes in body mass index (BMI) and percentage predicted forced expiratory volume in one second (FEV1) and calculated relative risk (RR) to compare pulmonary exacerbations (PEx) between pwCF enrolled in the CF Foundation Patient Registry with at least one in-person clinic visit after March 15 in both 2019 and 2020. Results: Overall, the proportion of clinical encounters that were in-person clinic visits decreased from 91% in 2019 to a low of 9% in April 2020. Among pwCF seen after March 15 in both 2019 and 2020, the mean (95% confidence interval [CI]) FEV1 percentage predicted was 1.3% (0.1-2.4) predicted higher in 2020 for children 6 to <12 years of age, and 7.5% (7.1-7.9) predicted higher in 2020 among pwCF ⩾12 years of age eligible for the highly effective CF transmembrane conductance regulator modulator, elexacaftor-tezacaftor-ivacaftor (ETI). There was no difference in FEV1 percentage predicted for pwCF ⩾12 years of age who were not eligible for ETI. Similarly, the mean (95% CI) BMI was 2.4 (2.0-2.8) percentile higher in 2020 for children 6 to <12 years of age and 5.2 (4.8-5.7) percentile higher in 2020 among children 12 to <18 years of age eligible for ETI. Mean (95% CI) BMI was 1.2 (1.2-1.3) (kg/m2) higher for pwCF ⩾18 years of age eligible for ETI, and 0.2 (0.1-0.3) (kg/m2) higher for pwCF ⩾18 years of age not eligible for ETI. The proportion of in-person clinic visits where any PEx was present was lower in 2020 compared with 2019, 25% compared with 38%, RR 0.82 (0.79-0.86). Conclusions: The care of pwCF was substantially changed during the spring 2020 peak of the COVID-19 pandemic. Among pwCF seen in-person in both 2019 and 2020 after the spring peak of the COVID-19 pandemic, lung function and BMI were higher in 2020 for children 6 to <12 years of age and pwCF eligible for ETI.

Remote monitoring in telehealth care delivery across the U.S. cystic fibrosis care network.

BACKGROUND: Cystic fibrosis (CF) programs and people with CF (PwCF) employed various monitoring methods for virtual care during the COVID-19 pandemic. This paper characterizes experiences with remote monitoring across the U.S. CF community. METHODS: The CF Foundation (CFF) sponsored distribution of home spirometers (April 2020 to May 2021), surveys to PwCF and CF programs (July to September 2020), and a second program survey (April to May 2021). We used mixed methods to explore access, use, and perspectives regarding the use of remote monitoring in future care. RESULTS: By October 2020, 13,345 spirometers had been distributed, and 19,271 spirometers by May 2021. Programs (n=286) estimated proportions of PwCF with home devices increased over seven months: spirometers (30% to 70%), scales (50% to 70%), oximeters (5% to 10%) with higher estimates in adult programs for spirometers and oximeters. PwCF (n=378) had access to scales (89%), followed by oximeters (48%) and spirometers (47%), often using scales and oximeters weekly, and spirometers monthly. Over both surveys, some programs had no method to collect respiratory specimens for cultures associated with telehealth visits (47%, n=132; 41%, n=118). Most programs (81%) had a process for phlebotomy associated with a telehealth visit, primarily through off-site labs. Both PwCF and programs felt future care should advance remote monitoring and recommended improvements for access, training, and data collection systems. CONCLUSIONS: PwCF and programs experienced unprecedented access to remote monitoring and raised its importance for future care. Improvements to current systems may leverage these shared experiences to augment future care models.

Barriers and facilitators to implementing telehealth services during the COVID-19 pandemic: A qualitative analysis of interviews with cystic fibrosis care team members.

BACKGROUND: The COVID-19 pandemic forced cystic fibrosis (CF) care programs to rapidly shift from in-person care delivery to telehealth. Our objective was to provide a qualitative exploration of facilitators and barriers to: 1) implementing high-quality telehealth and 2) navigating reimbursement for telehealth services. METHODS: We used data from the 2020 State of Care CF Program Survey (n=286 U.S. care programs) administered in August-September to identify two cohorts of programs, with variation in telehealth quality (n=12 programs) and reimbursement (n=8 programs). We conducted focus groups and semi-structured interviews with CF program directors and coordinators in December 2020, approximately 9 months from onset of the pandemic. We used the Consolidated Framework for Implementation Research to identify facilitators and barriers of implementation, and inductive thematic analysis to identify facilitators and barriers of reimbursement. RESULTS: Factors differentiating programs with greater and lower perceived telehealth quality included telehealth characteristics (perceived advantage over in-person care, cost, platform quality); external influences (needs and resources of those served by the CF program), characteristics of the CF program (compatibility with workflows, relative priority, available resources); characteristics of team members (individual stage of change), and processes for implementation (engaging patients and teams). Reimbursement barriers included documentation to optimize billing; reimbursement of multi-disciplinary team members, remote monitoring, and telephone-only telehealth; and lower volume of patients. CONCLUSIONS: A number of factors are associated with successful implementation and reimbursement of telehealth. Future efforts should provide guidance and incentives that support telehealth delivery and infrastructure, share best practices across CF programs, and remove barriers.

Reduction of pulmonary exacerbations in young children with cystic fibrosis during the COVID-19 pandemic.

To assess the impact of COVID-19 restrictions on cystic fibrosis (CF) pulmonary exacerbations (PEx) we performed a retrospective review of PEx events at our CF Center and compared the rate of PEx in 2019 versus 2020. Restrictions on social interaction due to the COVID-19 pandemic were associated with a lower number of PEx events at our pediatric CF Center, suggesting that these restrictions also reduced exposure to other respiratory viral infection in children with CF.

Identification of potential inhibitors of SARS-CoV-2 main protease from Aloe vera compounds: A molecular docking study.

SARS-CoV-2 is the pathogen agent of the new corona virus disease that appeared at the end of 2019 in China. There is, currently, no effective treatment against COVID-19. We report in this study a molecular docking study of ten Aloe vera molecules with the main protease (3CLpro) responsible for the replication of coronaviruses. The outcome of their molecular simulation and ADMET properties reveal three potential inhibitors of the enzyme (ligands 6, 1 and 8) with a clear preference of ligand 6 that has the highest binding energy (-7.9 kcal/mol) and fully obeys the Lipinski's rule of five.