Résilience - COVID-19 - Résilience - Coronavirus disease 2019

COVID-19 Related Anosmia Recovery – CORAR

Submission summary

By the end of 2021, there likely will be hundreds of millions of people infected with COVID-19 worldwide. The loss of smell (anosmia) will affect more than half of them. While most of them will rapidly recover their sense of smell, about 10% will not 6 months after the onset of the disease. Thus millions of people will suffer of long lasting anosmia linked to COVID-19. As this sense is among others very important for food intake, its loss will have a very important impact on life quality. While the cellular events leading to anosmia begin to be unravelled, its origin remains to be explored. The ability to detect odours starts in the olfactory neuroepithelium localized in the dorsal part of the nasal cavity. This neuroepithelium is composed mainly of olfactory neurons detecting odours, supportive cells and basal cells enabling a continuous regeneration of the epithelium. Among these cells, only the supportive cells express the receptors required for SARS-CoV-2 infection. Using the golden Syrian hamster as a model, it was shown that only 2 days after nasal instillation of SARS-CoV-2, supporting cells are massively infected by the virus. Furthermore, the olfactory epithelium structure is profoundly altered by the virus presence with most of the epithelium being desquamated. Along the disorganization of the olfactory epithelium, there is an important invasion of immune cells. The role of the immune cells in this process is not explored yet. Are they actively participating in the elimination of the infected cells? Are they present following cellular death induced by the virus to ensure its clearance? Following the disorganization of the olfactory epithelium induced by SARS-CoV-2 infection, it regenerates rapidly thanks to basal cells. After 14 days, approximately 50% of the epithelium is recovered and it is almost completely repaired in 21 days. This regeneration kinetic of the olfactory epithelium is consistent with the fast recovery of most COVID-19 related anosmia occurring for 40% of the patients in less than two weeks. However it cannot explain why 10% of these patients are still suffering from olfactory disturbance at 6 months following the onset of the disease. Clinicians treat the COVID-19 anosmic patients empirically by corticoids and/or by olfactory training but without any evidence of the effectiveness of these treatments on olfactory epithelium recovery. As corticoid treatments are known to reduce inflammation, their use could limit the desquamation of the olfactory epithelium if immune cells are active in this process. However, immune cells are also known to help the regeneration of the olfactory epithelium and the use of corticoid may thus disturb the recovery of olfaction. Using golden Syrian hamster as a model, the present project aims at: 1/Understanding the role of the immune system in the desquamation of the olfactory epithelium. 2/ Explore precisely the kinetic of the olfactory epithelium recovery from basal cells. 3/ Study the efficiency of corticoid treatment and/or olfactory training in order to improve the recovery from anosmia. Our study will improve our knowledge of the importance of immune cells in the COVID-19 related anosmia and its recovery as well as the efficiency of currently used treatment at a cellular level.

Project coordination

Nicolas Meunier (Unité de recherche Virologie et Immunologie Moléculaires)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

VIM Unité de recherche Virologie et Immunologie Moléculaires
Virologie

Help of the ANR 79,999 euros
Beginning and duration of the scientific project: August 2021 - 12 Months

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