Understanding the Potential Impact of Different Drug Properties On SARS-CoV-2 Transmission and Disease Burden: A Modelling Analysis

Background The public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods Using a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. Results The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions Advances in the treatment of COVID-19 to date have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority

Understanding the potential impact of different drug properties on SARS-CoV-2 transmission and disease burden : a modelling analysis

Q1Q1Background The unprecedented public health impact of the COVID-19 pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. Methods and Findings develop a mathematical model of SARS-CoV-2 transmission, COVID-19 disease and clinical care to explore the potential public-health impact of a range of different potential therapeutics, under a range of different scenarios varying: i) healthcare capacity, ii) epidemic trajectories; and iii) drug efficacy in the absence of supportive care. In each case, the outcome of interest was the number of COVID-19 deaths averted in scenarios with the therapeutic compared to scenarios without. We find the impact of drugs like dexamethasone (which are delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in highincome countries but only 8% in low-income countries (assuming R=1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalisation) could have much greater benefits, particularly in resource-poor settings facing large epidemics. Conclusions There is a global asymmetry in who is likely to benefit from advances in the treatment of COVID-19 to date, which have been focussed on hospitalised-patients and predicated on an assumption of adequate access to supportive care. Therapeutics that can feasibly be delivered to those earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priorityRevista Internacional - Indexad

Implementation of global antimicrobial resistance surveillance system (GLASS) in patients with bacteremia.

The global antimicrobial resistance surveillance system (GLASS) was launched by the World Health Organization (WHO) in 2015. GLASS is a surveillance system for clinical specimens that are sent to microbiology laboratory for clinical purposes. The unique feature of GLASS is that clinical data is combined with microbiological data, and deduplication of the microbiological results is performed. The objective of the study was to determine feasibility and benefit of GLASS for surveillance of blood culture specimens. GLASS was implemented at Siriraj Hospital in Bangkok, Thailand using a locally developed web application program (app) to transfer blood culture specimen data, and to enter clinical data of patients with positive blood culture by infection control nurses and physicians via the app installed in their smart phones. The rate of positive blood culture specimens with true infection was 15.2%. Escherichia coli was the most common cause of bacteremia. Secondary bacteremia, primary bacteremia, and central line-associated blood stream infection was observed in 61.8%, 30.6%, and 12.6% of cases, respectively. Sepsis was observed in 56.9% of patients. E.coli was significantly more common in community-acquired bacteremia, whereas Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii were significantly more common in hospital-acquired bacteremia. Hospital-acquired isolates of E.coli, K.pneumoniae, A.baumannii, P.aeruginosa, S.aureus and Enterococcus faecium were more resistant to antibiotics than community-acquired isolates. In-hospital mortality was significantly higher in patients with antibiotic-resistant bacteremia than in patients with antibiotic non-resistant bacteremia (40.5% vs. 28.5%, p<0.001). The patients with antibiotic-resistant bacteremia consumed more resources than those with antibiotic non-resistant bacteremia. Blood culture results combined with patient clinical data were shown to have more benefit for surveillance of antimicrobial resistance, and to be more applicable for developing local antibiotic treatment guidelines for patients suspected of having bacteremia. However, GLASS consumed more time and more resources than the conventional laboratory-based surveillance system

A multiplexed Cas13-based assay with point-of-care attributes for simultaneous COVID-19 diagnosis and variant surveillance

Point-of-care (POC) nucleic acid detection technologies are poised to aid gold-standard technologies in controlling the COVID-19 pandemic, yet shortcomings in the capability to perform critically needed complex detection—such as multiplexed detection for viral variant surveillance—may limit their widespread adoption. Herein, we developed a robust multiplexed clustered regularly interspaced short palindromic repeats (CRISPR)-based detection using LwaCas13a and PsmCas13b to simultaneously diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pinpoint the causative SARS-CoV-2 variant of concern (VOC)—including globally dominant VOCs Delta (B.1.617.2) and Omicron (B.1.1.529)—all the while maintaining high levels of accuracy upon the detection of multiple SARS-CoV-2 gene targets. The platform has several attributes suitable for POC use: premixed, freeze-dried reagents for easy use and storage; convenient direct-to-eye or smartphone-based readouts; and a one-pot variant of the multiplexed detection. To reduce reliance on proprietary reagents and enable sustainable use of such a technology in low- and middle-income countries, we locally produced and formulated our own recombinase polymerase amplification reaction and demonstrated its equivalent efficiency to commercial counterparts. Our tool—CRISPR-based detection for simultaneous COVID-19 diagnosis and variant surveillance that can be locally manufactured—may enable sustainable use of CRISPR diagnostics technologies for COVID-19 and other diseases in POC settings