Lancet Microbe
November 2024
Dysregulated host immune responses contribute to disease severity and worsened prognosis in COVID-19 infection and the underlying mechanisms are not fully understood. In this study, we observed that IL-33, a damage-associated molecular pattern molecule, is significantly increased in COVID-19 patients and in SARS-CoV-2-infected mice. Using IL-33 mice, we demonstrated that IL-33 deficiency resulted in significant decreases in bodyweight loss, tissue viral burdens, and lung pathology.
View Article and Find Full Text PDFRecent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of HS in several pathological processes and provided a rationale for considering the therapeutic implications of HS in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing HS donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus.
View Article and Find Full Text PDFTexas is a geographically large state with large human and livestock populations, many farms, a long coastal region, and extreme fluctuations in weather. During the last 15 years, the state of Texas has frequently suffered disasters or catastrophes causing extensive morbidity and economic loss. These disasters often have complicated consequences requiring multi-faceted responses.
View Article and Find Full Text PDFThe Delta variant of SARS-CoV-2 has caused many breakthrough infections in fully vaccinated individuals. While vaccine status did not generally impact the number of viral RNA genome copies in nasopharyngeal swabs of breakthrough patients, as measured by Ct values, it has been previously found to decrease the infectious viral load in symptomatic patients. We quantified the viral RNA, infectious virus, and anti-spike IgA in nasopharyngeal swabs collected from individuals asymptomatically infected with the Delta variant of SARS-CoV-2.
View Article and Find Full Text PDFBackground: The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT affected progression throughout hospitalization and utilization of intensive respiratory therapies.
Methods: We characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment.
Background: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19.
Methods: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site).
Background: Routine collection of patient-reported outcomes is needed to better understand recovery, benchmark between trauma centers and systems, and monitor outcomes over time. A key component of follow-up methodology is the mode of administration of outcome measures with multiple options available. We aimed to quantify patient preference and compare the response rates and data completeness for telephone and online completion in trauma patients.
View Article and Find Full Text PDFBackground: The number of trauma patients taking anticoagulants and antiplatelet agents is increasing as society ages. However, there have been limited and inconsistent reports of the association between anticoagulants and mortality and functional outcomes. This study aimed to quantify the association between anticoagulant/antiplatelet medication at the time of injury and both short-term and longer-term outcomes in older major trauma patients.
View Article and Find Full Text PDFBackground: The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death.
Methods: We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1.
Objective: Trauma is one of the most common contributors to maternal and foetal morbidity and mortality. The aim of the present study was to describe the characteristics and outcomes of major trauma in pregnant patients using a population-based registry.
Methods: Registry-based study using data from the Victorian State Trauma Registry (VSTR), a population-based database of all hospitalised major trauma (death due to injury, Injury Severity Score [ISS] ≥12, admission to an intensive care unit [ICU] for more than 24 h and requiring mechanical ventilation for at least part of their ICU stay or urgent surgery) in Victoria, Australia, from 1 July 2007 to 30 June 2019.
Background: Free Open-Access Medical education (FOAM) use among residents continues to rise. However, it often lacks quality assurance processes and residents receive little guidance on quality assessment. The Academic Life in Emergency Medicine Approved Instructional Resources tool (AAT) was created for FOAM appraisal by and for expert educators and has demonstrated validity in this context.
View Article and Find Full Text PDFThere is an urgent need for inexpensive, rapid and specific antigen-based assays to test for vaccine efficacy and detect infection with SARS-CoV-2 and its variants. We have identified a small, synthetic protein (JS7), representing a region of maximum variability within the receptor binding domain (RBD), which binds antibodies in sera from nine patients with PCR-verified COVID-19 of varying severity. Antibodies binding to either JS7 or the SARS-CoV-2 recombinant RBD, as well as those that disrupt binding between a fragment of the ACE2 receptor and the RBD, are proportional to disease severity and clinical outcome.
View Article and Find Full Text PDFAim: The purpose of this perspective is to review the options countries have to exit the draconian "lockdowns" in a carefully staged manner.
Methods: Experts from different countries experiencing Corona Virus Infectious Disease 2019 (COVID-19) reviewed evidence and country-specific approaches and the results of their interventions.
Results: Three factors are essential: 1.
Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients. To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates. This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI.
View Article and Find Full Text PDFBackground: Trauma is a leading cause of mortality. Holistic views of trauma systems consider injury as a public health problem that requires efforts in primary, secondary and tertiary prevention. However, the performance of trauma systems is commonly judged on the in-hospital mortality rate.
View Article and Find Full Text PDFThe American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society's journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.
View Article and Find Full Text PDFBackground: Reviewing prehospital trauma deaths provides an opportunity to identify system improvements that may reduce trauma mortality. The objective of this study was to identify the number and rate of potentially preventable trauma deaths through expert panel reviews of prehospital and early in-hospital trauma deaths.
Methods: We conducted a retrospective review of prehospital and early in-hospital (<24 h) trauma deaths following a traumatic out-of-hospital cardiac arrest that were attended by Ambulance Victoria (AV) in the state of Victoria, Australia, between 2008 and 2014.
The 2013-2016 epidemic of Ebola virus disease (EVD) that originated in West Africa underscored many of the challenges to conducting clinical research during an ongoing infectious disease epidemic, both in the most affected countries of Guinea, Liberia, and Sierra Leone, as well as in the United States and Europe, where a total of 27 patients with EVD received care in biocontainment units. The Special Pathogens Research Network (SPRN) was established in the United States in November 2016 to provide an organizational structure to leverage the expertise of the 10 Regional Ebola and Other Special Pathogen Treatment Centers (RESPTCs); it was intended to develop and support infrastructure to improve readiness to conduct clinical research in the United States. The network enables the rapid activation and coordination of clinical research in the event of an epidemic and facilitates opportunities for multicenter research when the RESPTCs are actively caring for patients requiring a biocontainment unit.
View Article and Find Full Text PDFEmerging and re-emerging infectious diseases pose growing global public health threats. However, research on and development of medical countermeasures (MCMs) for such pathogens is limited by the sporadic and unpredictable nature of outbreaks, lack of financial incentive for pharmaceutical companies to develop interventions for many of the diseases, lack of clinical research capacity in areas where these diseases are endemic, and the ethical dilemmas related to conducting scientific research in humanitarian emergencies. Hence, clinicians providing care for patients with emerging diseases are often faced with making clinical decisions about the safety and effectiveness of experimental MCMs, based on limited or no human safety, preclinical, or even earlier product research or historical data, for compassionate use.
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