https://orcid.org/0000-0003-0420-7191
ABSTRACT
Coronavirus disease (COVID-19) is a highly contagious infection caused by a recently identified coronavirus. The first known case was discovered in December 2019 in Wuhan, China. Since then, the illness has spread globally, resulting in an ongoing epidemic. Here, we would like to address one of the most pressing and outstanding questions which rise about COVID-19 during the year and a half since its discovery: what have we learned from COVID-19?
To the Editor:
The SARS-CoV lineage apparently has been circulating in bats for decades. It has been evolving to be capable of replicating in human cells and causing illness without further adaptation. Other coronaviruses are still circulating among bats and waiting to be discovered.Citation1 If we want to prevent another epidemic in the future, we have to start by identifying and evaluating viruses or pathogens in animals before they affect humans. Human health care costs can be reduced by investing more in studying animals. The bat coronavirus RaTG13 was identified in 2013 in Yunnan, China, from the Rhinolophus affinis bat. It is the most similar to SARS-CoV-2, with a 96% genome similarity.Citation2 Studying RaTG13 upon its discovery might have given us six years to prevent the pandemic.
Our comprehension of immunity to SARS-CoV-2 is improving along with the development of vaccines and drug interventions. Assays for assessing naturally acquired immunity and evaluating the effectiveness of immune therapies are essential to this development. A SARS-CoV-2 prophylaxis test can be performed by models and assays, and growth intervention can be achieved by modifying existing strategies. For example, the effects of treatments on the average virus growth and decay should be measured instead of the peak virus load to provide a better metric for various models. Comparing these effects is a straightforward way to predict treatment effectiveness.
The human coronavirus cannot infect mice without heavy genetic editing and by using the human receptor gene in a transgenic mouse model. Practically, the results in mice are in contrast to the results observed in humans. For example, IFNB1 expression increased in studying human lung infection such as human lung-only mice (LoM). In contrast, no such increase was observed in the lungs of COVID-19 patients and postmortem. In this regard, an in vitro study showed that IFNB1 expression was blocked at the time of SARS-CoV infection.Citation3,Citation4 Moreover, limited data from mice are found in studies on vaccines such as AstraZeneca from the UK, Inovio Pharmaceuticals from Korea, and Novavax from the USA. As a treatment strategy, a drug or naroparcil needs to be used to reprogram human organs.
We have to keep in mind that human infection may still not be simulated completely despite the high accuracy of the metric of immune pathway interaction in animal models and assays either in vivo or in vitro. This problem may also occur even though the experiment method is highly valid and sophisticated, thus providing the wrong guidance for defining the priorities in human immune pathway interaction. Safety associations in clinical cohorts need to be identified. Until we do so, however, our present methodology must focus on predictions and make assumptions on the basis of other virus infections.
Consequently, a smart way to deal with the utilization and analysis of current systems could dramatically boost our knowledge and ability to predict the effect of immune interaction pathways on SARS-CoV-2 infection. The mouse is the best model for studying general mechanisms and will remain so for the foreseeable future. Gene expression in mouse models and that in humans closely resembles each other. However, major species differences still exist, which may sometimes produce misleading findings and false positive or false negative results.
Author contribution
MA and AAE wrote the manuscript and designed the study, contributed to manuscript revision. All authors approved the final version.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Additional information
Funding
References
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