As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)–dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients.
Vibrio vulnificus remains one of the deadliest waterborne pathogens, yet little is known of the ecology that drive outbreaks. As a nationally notifiable disease, all cases of Vibrio vulnificus diagnosed in the United States are reported to the state in which they occurred, as well as the Centers for Disease Control (CDC) in Atlanta, Georgia. Given that the state of Florida is a 'hotspot' for Vibrio vulnificus in the United States, we examined the prevalence and incidence of cases reported to the Florida Department of Health (2008-2020). Using a dataset comprised of 448 cases of disease caused by Vibrio vulnificus infection, we identified environmental variables that were associated with clinical cases and deaths. Combined with data from the National Oceanic and Atmospheric Administration (NOAA), we developed statistical models to examine the relationship between meteorological measurements such as wind speed, air temperature, water temperature, and sea-level pressure. We then examined the association of those meteorological variables with coastal cases of Vibrio vulnificus, including the outcome, survival, or death. Between 2008 and 2020, Vibrio vulnificus cases generally increased over time, peaking in 2017. Not surprisingly, there appears to be a strong correlation between water temperature and air temperature in Florida. However, as water temperature and air temperature increased, so too did the likelihood that an infection with Vibrio vulnificus would lead to patient death. Interestingly, we also found that as mean wind speed and sea-level pressure decreased, the probability that a Vibrio vulnificus case would be reported increased. Given these results, we discuss the potential factors that may contribute to the observed correlations. We further speculate that the meteorological variables we measured may increase in importance as they relate to the incidence of Vibrio vulnificus in light of rising global temperatures.
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