Applying principles of patient blood management during COVID-19 pandemic: a literature review

As of 15 December 2021, coronavirus disease 2019 (COVID-19) affected approximately 271 million and killed 5.3 million people globally. COVID-19 pandemic had a tremendous impact on world healthcare systems and blood supply. While principles of patient blood management (PBM) may have been previously implemented in many jurisdictions, their widespread adoption has become imperative during the pandemic. This review will discuss the impact of the COVID-19 pandemic on the Canadian blood supply and how the principles of PBM could be applied during a pandemic or other disruptions to healthcare delivery or blood supply. We described the local blood system and how it adapted during the pandemic. We also included a discussion of pandemic-associated local PBM challenges and solutions. We conducted a brief review of English language literature with a specific focus on the application of PBM to reduce unnecessary red blood cell (RBC) transfusions in elective major surgery, hematological malignancies, elective major gynecological surgery and obstetrics between January 2020 and April 2022. The common themes included anemia diagnosis and management, restrictive RBC transfusion strategies and reduction in blood loss. Anemia is common, is frequently caused by iron deficiency and can be treated with oral or intravenous iron. Erythropoiesis stimulating agents are effective in raising hemoglobin and may be indicated in certain perioperative settings. Evidence supports the use of restrictive RBC transfusion thresholds and single unit transfusions in most patient populations. Hemostatic therapy, such as tranexamic acid, is generally safe and effective in reducing bleeding. Diagnostic phlebotomy contributes to anemia and should be restricted to tests that are necessary and likely to change management. In conclusion, PBM interventions are generally effective and safe. Prioritization of PBM during the pandemic or a blood shortage may help sustain the blood supply and lead to improved patient outcomes.Copyright © Annals of Blood. All rights reserved.

Model-informed Dose Selection of Dual Toll-like Receptor 7/8 Inhibitor Enpatoran (M5049) for the Treatment of COVID-19 Pneumonia

Background. Enpatoran, formerly known as M5049, is a potential first-in-class small molecule antagonist of toll-like receptors (TLR) 7 and 8, which may prevent viral-associated hyperinflammatory response and progression to 'cytokine storm' in coronavirus disease 2019 (COVID-19) patients. The objective of this study was to leverage existing population pharmacokinetic/pharmacodynamic (popPK/PD) models for enpatoran to inform dose selection for an accelerated Phase II study in COVID-19 patients with pneumonia. Methods. The popPK/PD models were based on plasma PK and PD biomarker (ex vivo-stimulated interleukin [IL]6 and interferon α [IFNα] secretion) data from the enpatoran first-in-human Phase I study in healthy participants (Port A, et al. Lupus Sci Med 2020;7(Suppl. 1): P135). A two-compartment model describing PK used a sigmoidal Emax model with proportional decrease from baseline characterizing the PD response across the investigated single and multiple daily dose range of 1-200 mg (N=72). Concentrations that inhibited 50% and 90% (IC50/IC90) of cytokine secretion were estimated and stochastic simulations were performed to assess target coverage under different dosing regimens. Results. Simulations suggested that, to achieve maximal inhibition of IL-6 over time, enpatoran PK concentrations would be maintained above the IC90 throughout the dosing interval with doses of 100 mg and 50 mg twice daily in 90% and 30% of participants, respectively. In comparison, IFNα inhibition was predicted to be lower, with IC90 coverage in 60% and 8% of participants with twice daily doses of 100 mg and 50 mg enpatoran, respectively. Conclusion. Utilization of existing popPK/PD models allowed for the accelerated development of enpatoran in COVID-19 to address an unprecedented global pandemic. Rational model-informed dose selection was supported by data from a Phase I study in which there were no safety concerns.

Utility of hydrogen peroxide disinfection in decreasing pathogens in a critical care environment

INTRODUCTION: Environmental surfaces impact pathogen transmission and thus hospital acquired infections. This underscores the need for high-level disinfection, especially considering the vulnerability of critical care patients and the risks posed by multi-drug resistant organisms (MDRO). Enhanced cleaning practices employed by hospitals for environmental disinfection are not all equal. For this investigation, a hydrogen peroxide disinfection system was chosen due to its EPA approval against SARS-CoV-2 and its sporicidal efficacy. This study sought to evaluate the efficacy/ feasibility of a hybrid form of hydrogen peroxide (HHP fogging) compared to current disinfection practices (standard cleaning and enhanced UV-light cleaning) in a critical care setting. METHODS: From Dec '20-Jun '21 data were collected in 17 critical care patient rooms post-discharge. Samples were collected to evaluate HHP fogging versus standard and enhanced cleaning. Sampling followed each intervention: post-EVS standard cleaning, post-enhanced cleaning with UV-light, and post HHP fogging following standard/enhanced practices. Five preset high touch patient room locations were swabbed for aerobic colony counts (ACC) and enumerated for MDRO presence: toilet, phone, bed rail, touchscreen, sink countertop. Measurements included quantitative and qualitative counts (ACC, adenosine triphosphate (ATP) swabs -measured in relative light units,RLU), hydrogen peroxide chemical indicators, and bacterial spore biological indicators(BIs, Geobacillus stearothermophilus). RESULTS: No difference was seen between standard cleaning and enhanced cleaning with UV light (mean ACC 7.16 and 6.35, respectively;p=0.186). HHP fogging reduced present ACC levels by 98% beyond current EVS post-discharge cleaning practices (mean ACC 0.137, p< 0.0001). MRSA instances were observed after standard and enhanced cleaning with UV light (mean ACC 0.178), no MRSA was detected after HHP fogging. ATP results showed an average 88% reduction post HHP fogging (mean RLU: post cleaning=9012, post HHP fogging=1109;p=0.014) and BIs confirmed a 6-log bacterial spore efficacy. CONCLUSION: HHP fogging resulted in successful elimination of MDROs and reduction in aerobic colony counts versus standard and UV-light cleaning. Deployment of HHP fogging is feasible and safe in a critical care setting.

Optimal Lockdown in a Commuting Network

We study optimal dynamic lockdowns against COVID-19 within a commuting network. Our framework integrates canonical spatial epidemiology and trade models and is applied to cities with varying initial viral spread: Seoul, Daegu, and the New York City metropolitan area (NYM). Spatial lockdowns achieve substantially smaller income losses than uniform lockdowns. In the NYM and Daegu with large initial shocks-the optimal lockdown restricts inflows to central districts before gradual relaxation, while in Seoul it imposes low temporal but large spatial variation. Actual commuting reductions were too weak in central locations in Daegu and the NYM and too strong across Seoul.

Automated Contact Tracing using Person Tracking and Re-Identification

This paper presents an implementation of contact tracing (a protocol followed to curtail the spread of viruses like Covid-19) using CCTV video footage from multiple cameras. The proposed system gives immediate insights about all the possible people at risk when a person under surveillance is clinically tested positive. This system automates the process of manual contact tracing by detecting contact between people under surveillance by estimating the distance between them, identifying them, and tracking their interactions. This data is then stored, filtered, and analyzed. A confusion matrix was derived from the videos that took into account true contacts, false contacts between people in the input video and whether the contacts in the video were considered as true contacts or false contacts according to the algorithm. This gave us insights about the algorithm's accuracy, precision and recall which were found to be 91%, 94% and 71% respectively. © 2021 IEEE.