Background
While risk of outdoor transmission of respiratory viral infections is hypothesized to be low, there is limited data of SARS-CoV-2 transmission in outdoor compared to indoor settings.
Methods
We conducted a systematic review of peer-reviewed papers indexed in PubMed, EMBASE and Web of Science and pre-prints in Europe PMC through August 12 th, 2020 that described cases of human transmission of SARS-CoV-2. Reports of other respiratory virus transmission were included for reference.
Results
Five identified studies found that a low proportion of reported global SARS-CoV-2 infections have occurred outdoors (<10%) and the odds of indoor transmission was very high compared to outdoors (18.7 times; 95% CI 6.0, 57.9). Five studies described influenza transmission outdoors and two described adenovirus transmission outdoors. There was high heterogeneity in study quality and individual definitions of outdoor settings which limited our ability to draw conclusions about outdoor transmission risks. In general, factors such as duration and frequency of personal contact, lack of personal protective equipment and occasional indoor gathering during a largely outdoor experience were associated with outdoor reports of infection.
Conclusion
Existing evidence supports the wide-held belief that the the risk of SARS-CoV-2 transmission is lower outdoors but there are significant gaps in our understanding of specific pathways.
There is an unmet need for economical snakebite therapies with long shelf lives that are effective even with delays in treatment. The orally bioavailable, heat-stable, secretory phospholipase A2 (sPLA2) inhibitor, LY333013, demonstrates antidotal characteristics for severe snakebite envenoming in both field and hospital use. A murine model of lethal envenoming by a Papuan taipan (Oxyuranus scutellatus) demonstrates that LY333013, even with delayed oral administration, improves the chances of survival. Furthermore, LY333013 improves the performance of antivenom even after it no longer reverses neurotoxic signs. Our study is the first demonstration that neurotoxicity from presynaptic venom sPLA2S can be treated successfully, even after the window of therapeutic antivenom has closed. These results suggest that sPLA2 inhibitors have the potential to reduce death and disability and should be considered for the initial and adjunct treatment of snakebite envenoming. The scope and capacity of the sPLA2 inhibitors ability to achieve these endpoints requires further investigation and development efforts.
There is a clear, unmet need for effective, lightweight, shelf-stable and economical snakebite envenoming therapies that can be given rapidly after the time of a snake’s bite and as adjuncts to antivenom therapies in the hospital setting. The sPLA2 inhibitor, LY315920, and its orally bioavailable prodrug, LY333013, demonstrate surprising efficacy and have the characteristics of an antidote with potential for both field and hospital use. The efficacy of the active pharmaceutical ingredient (LY315920) and its prodrug (LY333013) to treat experimental, lethal envenoming by Micrurus fulvius (Eastern coral snake) venom was tested using a porcine model. Inhibitors were administered by either intravenous or oral routes at different time intervals after venom injection. In some experiments, antivenom was also administered alone or in conjunction with LY333013. 14 of 14 animals (100%) receiving either LY315920 (intravenous) and/or LY333013 (oral) survived to the 120 h endpoint despite, in some protocols, the presence of severe neurotoxic signs. The study drugs demonstrated the ability to treat, rescue, and re-rescue animals with advanced manifestations of envenoming. Low molecular mass sPLA2 inhibitors were highly effective in preventing lethality following experimental envenoming by M. fulvius. These findings suggest the plausibility of a new therapeutic approach to snakebite envenoming, in this example, for the treatment of a coral snake species for which there are limitations in the availability of effective antivenom.
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