Applying Lessons Learned From COVID-19 Therapeutic Trials to Improve Future ALI/ARDS Trials.

Host-directed therapeutics targeting immune dysregulation are considered the most promising approach to address the unmet clinical need for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). To better understand the current clinical study landscape and gaps in treating hospitalized patients with severe or critical COVID-19, we identified COVID-19 trials developing host-directed therapies registered at ClinicalTrials.gov and discussed the factors contributing to the success vs failure of these studies. We have learned, instead of the one-size-fits-all approach, future clinical trials evaluating a targeted immunomodulatory agent in heterogeneous patients with ALI/ARDS due to COVID-19 or other infectious diseases can use immune-based biomarkers in addition to clinical and demographic characteristics to improve patient stratification and inform clinical decision-making. Identifying distinct patient subgroups based on immune profiles across the disease trajectory, regardless of the causative pathogen, may accelerate evaluating host-directed therapeutics in trials of ALI/ARDS and related conditions (eg, sepsis).

Vulnerability and fraud: evidence from the COVID-19 pandemic.

This study examines consumer fraud at the onset of the COVID-19 pandemic and provides novel evidence for the opportunity model of predatory victimization. Scammers have taken advantage of the COVID-19 pandemic shock to exploit victims who are already vulnerable and suffering. The number of fraud cases has greatly increased as COVID-19 spread across the U.S., consistent with the vulnerable-to-become-victimization hypothesis based on the opportunity model of predatory victimization. A Google Trends analysis shows that the increase in fraud and scams is attributable to victims' increased vulnerability rather than to their awareness of fraud and increased motivation to report scams. An improvement in financial literacy is associated with the reduction of finance-related fraud and scams. Finally, we provide important policy implications to protect people from fraud victimization.

Applying Lessons Learned From COVID-19 Therapeutic Trials to Improve Future ALI/ARDS Trials

Host-directed therapeutics targeting immune dysregulation are considered the most promising approach to address the unmet clinical need for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). To better understand the current clinical study landscape and gaps in treating hospitalized patients with severe or critical COVID-19, we identified COVID-19 trials developing host-directed therapies registered at ClinicalTrials.gov and discussed the factors contributing to the success vs failure of these studies. We have learned, instead of the one-size-fits-all approach, future clinical trials evaluating a targeted immunomodulatory agent in heterogeneous patients with ALI/ARDS due to COVID-19 or other infectious diseases can use immune-based biomarkers in addition to clinical and demographic characteristics to improve patient stratification and inform clinical decision-making. Identifying distinct patient subgroups based on immune profiles across the disease trajectory, regardless of the causative pathogen, may accelerate evaluating host-directed therapeutics in trials of ALI/ARDS and related conditions (eg, sepsis).

Does flattening the curve make a difference? An investigation of the COVID-19 pandemic based on an SIR model

We use a susceptible-infective-removed (SIR) model to examine the impacts of different isolation measures to combat the COVID-19 pandemic. The model predicts that strong isolation measures in the early stage of the pandemic can not only delay the time for the number of infections and deaths to reach the peak but also greatly reduce the cumulative number of infections and deaths. We verify the model predictions by using the simulation and the data of the COVID-19 cases. The results are independent of the joint distribution of the fatality rate and the initial number of active cases.

Identification of cGAS as an innate immune sensor of extracellular bacterium Pseudomonas aeruginosa.

Cyclic GMP-AMP synthase (cGAS) is reported essential for detecting intracellular bacteria. However, it remains to be determined whether and how cGAS is involved in extracellular bacterial infection. Here, we report that cGAS is essential for mediating type I interferon (IFN) production in infection by multiple extracellular pathogens, including Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. In addition, the canonical cGAS-stimulator of interferon gene (STING)-IFN axis is required for protecting mice from P. aeruginosa-induced mouse acute pulmonary infection, confirmed in cGAS pathway-specific gene deficiency mouse models. cGAS -/- and STING -/- mice exhibited reduced type I IFNs production, excessive inflammatory response accompanied with decreased resistance to P. aeruginosa challenge. Unfolded protein response was also modulated by cGAS through IRF3 and type I IFNs under P. aeruginosa infection. Collectively, these findings uncover the importance of cGAS in initiating immune responses against extracellular bacterial infection.