Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Use Associated with Reduced Mortality and Other Disease Outcomes in US Veterans with COVID-19.

OBJECTIVE: To determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans. PATIENTS AND METHODS: We retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19-positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19-positive case date. RESULTS: The overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61-0.98) and death within 60 days (0.87, 0.79-0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44-0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79-0.97) and an ARB only prescription (0.78, 0.67-0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19-positive case date (1.22, 1.02-1.46). CONCLUSION: In this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.

Binder design for targeting SARS-CoV-2 spike protein: An in silico perspective.

INTRODUCTION: The COVID-19 pandemic is now affecting all people around the world and getting worse. New antiviral medications are desperately needed other than the few approved medications that have shown no promising efficacy so far. METHODS: Here we report three blocking binders for targeting SARS-CoV-2 spike protein to block the interaction between the spike protein on the SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2) receptors, responsible for viral homing into the alveolar epithelium type II cells (AECII). RESULTS: The design process is based on the collected natural scaffolds and using Rosetta interface for designing the binders. CONCLUSION: Based on the structural analysis, three binders were selected, and the results showed that they might be promising as new therapeutic targets for blocking COVID-19.

Feasibility and acceptability of a structured quality by design approach to enhancing the rigor of clinical studies at an academic health center.

INTRODUCTION: Clinical trials are a critical step in the meaningful translation of biomedical discoveries into effective diagnostic and therapeutic interventions. Quality by design (QbD) is a framework for embedding quality into the design, conduct, and monitoring of clinical trials. Here we report the feasibility and acceptability of a process for implementing QbD in clinical research at an academic health center via multidisciplinary design studios aimed at identifying and prioritizing critical to quality (CTQ) factors. METHODS: The Clinical Trial Transformation Initiative's Principles Document served as a guide to identify and categorize key CTQ factors, defined as elements of a clinical trial that are critical to patient safety and data integrity. Individual trials were reviewed in CTQ design studios (CTQ-DS) and the feasibility and acceptability of this intervention was examined through post-meeting interviews and surveys. RESULTS: Eight clinical research protocols underwent the QbD evaluation process. The protocols ranged from multicenter randomized clinical trials to nonrandomized investigator-initiated studies. A developmental evaluation informed the iterative refinement of the CTQ-DS process, and post-meeting surveys revealed that CTQ-DS were highly valued by principal investigators (PIs) and resulted in multiple protocol changes. CONCLUSIONS: The present study demonstrated that QbD principles can be implemented to inform the design and conduct of clinical research at an academic health center using multidisciplinary design studios aimed at identifying and prioritizing CTQ elements. This approach was well received by the participants including study PIs. Future research will need to evaluate the effectiveness of this approach in improving the quality of clinical research.