Conclusions and future perspectives
Intensive efforts have been invested in the short timespan after the outbreak of COVID-19 to characterize and develop anti-SARS-CoV-2 therapeutics. Many drugs are being developed or being repurposed with varying degrees of success in in-vitro and clinical trials. As the speed of discovering the drugs and vaccines is increasing, understanding their safety and effectiveness is urgently needed to control the spread of the SARS-CoV-2 infection. However, many questions still need to be answered regarding the route of transmission of SARS-CoV-2. Are other routes like fecal, sexual or mother-to-child transmission involved? The disease has dynamic outcomes, which has made it challenging to understand the pathogenesis. Why does the disease have higher infectivity than MERS and SARS? Why are elderly people and people with underlying conditions more susceptible? There are many unknowns regarding the comorbidities and coinfections of SARS-CoV-2. Finally, there are questions as to why some repurposed antivirals or drugs are effective in some individuals in the treatment of COVID-19. In order to answer these questions, in vivo studies using the best animal models are needed because it is impossible to ask all these questions in human clinical studies. Because of the large variability in the genetic makeup of humans’ it is impossible to understand mechanisms. Animal models like ferrets, mice, and hamsters can aid in answering many questions pertaining to the mechanism of action of antivirals, efficacy and safety of vaccines and the impact of comorbidities on COVID-19 pathogenesis. Several animal models can be used to answer these questions; however, it is possible that no single animal will be able to answer all the human translational questions due to inherent differences in the development and physiology of the organism. Furthermore, there is a considerable amount of variability among the animals such as differences in their biology, genetics, level of ACE2 receptor expression, all of which can influence the rate of infection.