Virus World

The COVID-19 pandemic has prompted the search for animal models that recapitulate the pathophysiology observed in humans infected with SARS-CoV-2 and allow rapid and high throughput testing of drugs and vaccines. Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. Intranasal administration of SARS-CoV-2 S RBD in adult zebrafish recombinant protein caused severe olfactory and mild renal histopathology.

Zebrafish intranasally treated with SARS-CoV-2 S RBD became hyposmic within minutes and completely anosmic by 1 day to a broad-spectrum of odorants including bile acids and food. Single cell RNA-Seq of the adult zebrafish olfactory organ indicated widespread loss of expression of olfactory receptors as well as inflammatory responses in sustentacular, endothelial, and myeloid cell clusters. Exposure of wildtype zebrafish larvae to SARS-CoV-2 in water did not support active viral replication but caused a sustained inhibition of ace2 expression, triggered type 1 cytokine responses and inhibited type 2 cytokine responses. Combined, our results establish adult and larval zebrafish as useful models to investigate pathophysiological effects of SARS-CoV-2 and perform pre-clinical drug testing and validation in an inexpensive, high throughput vertebrate model.

Preprint available in bioRxiv (Nov. 8 , 2020):

https://doi.org/10.1101/2020.11.06.368191

Explore hospital bed use, need for intensive care beds, and ventilator use due to COVID-19 based on projected deaths for all 50 US states and District of Columbia.

Updated  projections (July 7) by the Institute of Health Metrics and Evaluation (IHME), now estimate over 208,000 total deaths in the United States by November first. These new numbers estimate 75,000 additional deaths will occur in the following 4 months. The model predicts that up to 40,000 deaths can be avoided by implementing universal wearing of face masks in the U.S. The model forecasts 600-700 daily deaths  in the U.S. through the summer, later increasing as we enter into the flu season.

By comparison, under easing mandates, near 1300 average daily deaths  are predicted by November in the U.S. The model also estimates significant burden of disease in Brazil,  with 176,000 cumulative  deaths by the first of November.

The next Ebola outbreak could be predicted using a new UCL-developed model that tracks how changes to ecosystems and human societies combine to affect the spread of the deadly infectious disease. The model could help policymakers to decide where to target vaccine deployment, or develop healthcare infrastructure, to reduce the risk of zoonotic disease outbreaks—illnesses that spread between animals and humans.

Analysis using a mathematical model, published today in Nature Communications, shows that several countries in Africa, including Nigeria, could be at risk of Ebola outbreaks both presently, and in the future, despite having experienced no known cases to date. First author of the study, Dr. David Redding (UCL Genetics, Evolution & Environment), said: "It is vital that we understand the complexities causing animal-borne diseases to spill-over into humans, to accurately predict outbreaks and help save lives. "In our models, we've included more information about the animals that carry Ebola and, by doing so, we can better account for how changes in climate, land-use or human societies can affect human health." Designed by a UCL-led team of researchers, the model captures the impact of climate, land use and human population factors on the risk of Ebola and predicts the known set of previous outbreaks with a high degree of accuracy, even in the absence of case data. The results show that Ebola outbreaks, resulting from spill-over events, are 1.6 times more likely in scenarios with increased warming and slower socioeconomic development.

More than two thirds of all infectious diseases originate in animals, including Ebola, Lassa fever and West Nile virus. These diseases contribute to the global health and economic burden that disproportionately affects poor communities. The latest Ebola epidemic has claimed more than 2,100 lives since August 2018 and while there are signs it is in retreat, the risk of spread is still high according to a recent report by the UN....

"Ebola risk appears to worsen in future versions of our planet that have higher climate change and worse cooperation between societies. Working together to improve healthcare resources, which can contain dangerous diseases such as Ebola, appears to strongly reduce future risk, and this offers an important option for preventing future disease cases. We hope our model will help policy makers address this challenge."

Published in Nat. Communications on October 15, 2019:

https://doi.org/10.1038/s41467-019-12499-6