PT - JOURNAL ARTICLE AU - Aurora Kraus AU - Elisa Casadei AU - Mar Huertas AU - Chunyan Ye AU - Steven Bradfute AU - Pierre Boudinot AU - Jean-Pierre Levraud AU - Irene Salinas TI - A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 AID - 10.1101/2020.11.06.368191 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.11.06.368191 4099 - http://biorxiv.org/content/early/2020/11/08/2020.11.06.368191.short 4100 - http://biorxiv.org/content/early/2020/11/08/2020.11.06.368191.full AB - 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.Competing Interest StatementThe authors have declared no competing interest.