Recovery of Anosmia in Hamsters Infected With SARS-CoV-2 Is Correlated With Repair of the Olfactory Epithelium

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting millions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.

SARS-CoV-2 infection in hamsters and humans results in lasting and unique systemic perturbations after recovery

“…Alternatively, SARS-CoV-2 infection of olfactory bulbs may result in loss of a physical barrier, enabling the introduction of microbiome commensals which could contribute to the inflammatory profile. This latter hypothesis is supported by recent evidence that SARS-CoV-2 can induce gross morphological changes in the olfactory epithelium characterized by thinning and sloughing of the tissue that would normally prevent bacterial commensals from interacting with the OB (96). The extent to which the olfaction system contributes to the persistent inflammatory processes described within our study remains to be determined.…”

The nervous system during COVID‐19: Caught in the crossfire

“…Olfactory sensory neurons are one of the cell types that are sloughed into the lumen so the loss of these neurons may alter normal olfaction. A study with SARS‐CoV‐2 (WA1) ‐infected Syrian hamsters asserts that the sloughing of the olfactory neuroepithelium thickness along the ethmoid turbinates negatively correlates with olfactory function, according to a buried food test 219 . The intensity of sloughing along the olfactory neuroepithelium could be a measure to predict the duration of prolonged anosmia following infection.…”

“…Meanwhile, the buried food test has been relied upon to study SARS‐CoV‐2‐induced anosmia with rodent models. SARS‐CoV‐2 (A‐D) ‐infected humanized mice and hamsters have exhibited “decreased olfactory function” by finding buried food less often during infection 175,176,219 . However, the buried food test has major caveats and there are problems with how the behavior test was performed in these studies.…”

In Response to Clinical Features of Parosmia Associated with COVID‐19 Infection

“…To date, research studies were mainly limited to the study of OD in the course of infection, which are mostly quantitative. The most recent theories emerging from histopathological studies on animal models 2-4 and humans 5,6 correlate these disorders to damage to the olfactory neuroepithelium (ONE) without involvement of the olfactory bulb. 2 In the same way, the recovery of the olfactory function may occur through the regeneration of the ONE, which takes place starting from the basal cells 5 and takes about 30 days.…”

“…The most recent theories emerging from histopathological studies on animal models 2-4 and humans 5,6 correlate these disorders to damage to the olfactory neuroepithelium (ONE) without involvement of the olfactory bulb. 2 In the same way, the recovery of the olfactory function may occur through the regeneration of the ONE, which takes place starting from the basal cells 5 and takes about 30 days. 7 The regeneration of the olfactory neurons is fundamental for the quantitative recovery of the olfactory function, but it is not sufficient for this perception to be qualitatively normal.…”