Zebrafish as a translational model: an experimental alternative to study the mechanisms involved in anosmia and possible neurodegenerative aspects of COVID-19?

The Coronavirus Disease - 2019 (COVID-19) presents a variability of clinical symptoms, ranging from asymptomatic to severe respiratory and systemic conditions. In a cohort of patients, the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), beyond the classical respiratory manifestations, induces anosmia. Evidence has suggested SARS-CoV-2-induced anosmia can be the result of neurodegeneration of the olfactory pathway. Neurological symptoms associated with COVID-19 have been reported; however, the precise mechanism and possible long-lasting effects remain poorly investigated. Preclinical models are valuable tools for describing and testing new possible treatments for neurological disorders. In this way, the zebrafish (Danio rerio) organism model represents an attractive tool in the field of neuroscience, showing economic and logistical advantages besides genetic and physiologic similarities with mammalian, including the brain structure and functions. Besides, its external embryonic development, high availability of eggs, and fast development allows easy genetic manipulation and fast replications. In the present review, we suggest that the zebrafish model can be advantageous to investigate the neurological features of COVID-19.SIGNIFICANCE STATEMENTThe Coronavirus Disease - 2019 (COVID-19) is characterized not only by respiratory, but also neurological symptoms that may persevere even longer than the respiratory condition. However, some questions remain unanswered. How does the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enter the brain? Which brain regions are infected? How does the virus affect our behavioral and sensorial responses? Can the brain infection induce alterations that last longer? We propose that the zebrafish is a suitable model to study the effects of SARS-CoV-2 in the brain, especially because of the similarities between the fish' and the human brain. Zebrafish is a cheap animal model and several reproducible and fast animal tests can be used to investigate its behavioral and sensory functions.