COVID-19: The Mechanisms of Olfactory Loss Finally Explained by French Researchers

Since the onset of the Covid-19 pandemic, the loss of the sense of smell has been one of the most common symptoms. However, the mechanisms involved in anosmia have not been elucidated until now. A French research team has identified the different stages of the disease. SARS-CoV-2 infects sensory neurons and causes persistent inflammation of the epithelium and the olfactory nervous system.

Woman Smelling Flower

Covid-19 caused by the SARS-CoV-2 virus is primarily a respiratory disease, but many patients also present with extra-respiratory symptoms. Among other symptoms, sudden loss of the sense of smell has been reported worldwide in people infected with SARS-CoV-2 since the beginning of the pandemic. The direct role of the virus in anosmia remains unclear to date. One of the generally accepted hypotheses has been that temporary edema in the olfactory bulb impedes the passage of the air carrying odor molecules to olfactory neurons (the famous “stuffy nose” sensation of the common cold).

In a new study, the results of which were published on May 3, 2021, in the journal Science Translational Medicine, researchers from the Institut Pasteur, CNRS, Inserm, and the University of Paris, AP-HP, have elucidated the mechanisms involved in Covid-19-related anosmia. The study was performed in patients with Covid-19 and was complemented by analyses in an animal model. Surprisingly, this study showed that conventional nasopharyngeal swabs can be negative even though the virus persists deep in the nasal cavity, in the olfactory epithelium. This result indicates that diagnosis of SARS-CoV-2 by nasal brushing can be considered in addition to regular nasopharyngeal swabbing in patients with olfactory loss.

This study also shows the mechanism of Covid-19-related loss of smell by showing the different steps chronologically:

The disappearance of cilia carried by sensory neurons following viral infection.
The presence of viruses in sensory neurons.
The disorganization of the olfactory epithelium associated with apoptosis. The epithelium is organized in regular lamellae that are destructured by coronavirus infection.
The invasion of the virus into the first brain relay of the olfactory system, the olfactory bulb.
The presence of neuroinflammation and viral RNA in multiple brain regions.

Persistent inflammation and long-lasting viruses in the olfactory epithelium.

This study demonstrates that the loss of the sense of smell is also the result of a degradation of the sensory organ. “Indeed, we discovered that the sensory neurons are infected by SARS-CoV-2, but also the olfactory nerve and the olfactory nerve centers of the brain,” comments Pierre-Marie Lledo, CNRS researcher, head of the Perception and Memory Unit (Institut Pasteur/CNRS) and co-author of the study.

“Another important point of this study is the observation in animal models showing that, once the virus enters the olfactory bulb, it spreads to other neuronal structures where it triggers a significant inflammatory response,” explains Hervé Bourhy, head of the Lyssavirus, Epidemiology and Neuropathology Unit at the Institut Pasteur and co-author of the study. The infection of olfactory neurons could therefore represent a gateway to the brain and explain why certain patients develop various clinical manifestations, both psychological (anxiety disorders, depression) and neurological (cognitive impairment, susceptibility to develop a neurodegenerative disease), which should be the subject of further studies.

Marc Lecuit, head of the Department of Infectious Biology (Institut Pasteur, INSERM) and co-author of the study, concludes, “According to our results, the loss of smell with Covid-19 can last several months in some patients, and this persistence of clinical manifestations is due to the persistence of the virus and inflammation in the olfactory mucosa.” These new findings should be taken into account when diagnosing and treating the long-term manifestations of Covid-19.