@article{3076369, title = "Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge", author = "Winkler, M.S. and Skirecki, T. and Brunkhorst, F.M. and Cajander, S. and Cavaillon, J.-M. and Ferrer, R. and Flohé, S.B. and García-Salido, A. and Giamarellos-Bourboulis, E.J. and Girardis, M. and Kox, M. and Lachmann, G. and Martin-Loeches, I. and Netea, M.G. and Spinetti, T. and Schefold, J.C. and Torres, A. and Uhle, F. and Venet, F. and Weis, S. and Scherag, A. and Rubio, I. and Osuchowski, M.F.", journal = "EBioMedicine", year = "2021", volume = "66", publisher = "Elsevier B.V.", issn = "2352-3964", doi = "10.1016/j.ebiom.2021.103291", keywords = "chemokine; corticosteroid; cytokine; neutralizing antibody; antivirus agent, airborne transmission; animal model; cell survival; cell therapy; clinical research; coronavirus disease 2019; cytokine release; disease severity; drug development; immune response; immunization; immunosuppressive treatment; immunotherapy; inflammation; inflammatory infiltrate; lethality; lung lavage; mortality; nonhuman; pandemic; phase 1 clinical trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 4 clinical trial (topic); phenotype; pneumonia; preclinical study; randomized controlled trial (topic); Review; Severe acute respiratory syndrome coronavirus 2; signal transduction; vaccination; virus load; virus replication; virus shedding; age; animal; clinical trial (topic); disease model; drug therapy; etiology; genetics; hamster; human; mouse; Mustela putorius furo; mutation; pathophysiology; pharmacology; primate; therapy, Age Factors; Animals; Antiviral Agents; Clinical Trials as Topic; COVID-19; COVID-19 Vaccines; Cricetinae; Disease Models, Animal; Ferrets; Humans; Mice; Mutation; Primates; SARS-CoV-2", abstract = "Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge. In this review, we characterize the existing animal models exposing their relevance and limitations as well as outline their utility in COVID-19 drug and vaccine development. Concurrently, we summarize the status of clinical trial research and discuss the novel tactics utilized in the largest multi-center trials aiming to accelerate generation of reliable results that may subsequently shape COVID-19 clinical treatment practices. We also highlight areas of improvement for animal studies in order to elevate their translational utility. In pandemics, to optimize the use of strained resources in a short time-frame, optimizing and strengthening the synergy between the preclinical and clinical domains is pivotal. © 2021 The Authors" }