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.