Smell and Taste Loss in COVID-19 is linked to Viral Staying Power in the Human Nose (Mystery solved)

Patients infected with COVID-19 often lose their sense of smell or taste, or both, particularly if their symptoms are mild. While research has focused on the causes of COVID-19 patients' lung infections, the causes of neurological symptoms have remained unknown.

Researchers have now elucidated the mechanisms underlying the loss of smell (anosmia) in SARS-CoV-2 patients at various stages of the disease.

This  article was published in Science Translational Medicine under title “COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters.”

SARS-CoV-2 induces loss of cilia in the nasal lining. [Source: Pierre-Marie Lledo/Institute Pasteur].

Scientists from the Institute Pasteur, CNRS, Inserm, University of Paris, and Assistance Publique – Hôpitaux de Paris examined the nasal linings of 11 COVID-19 patients who reported a loss of smell and found SARS-CoV-2 viral particles and inflammation in several cell types in the lining of the nasal cavity (olfactory neuroepithelium), including sensory neuron cells. SARS-CoV-2 infects and multiplies in the olfactory epithelium of hamsters and in individuals with COVID-19 for several months after infection, according to the researchers.

Golden Syrian hamsters contaminated with SARS-CoV-2 lose their sense of smell, according to the team led by Pierre-Marie Lledo, PhD. This is linked to virus spread in the nasal mucosa and central nervous system, as well as persistent inflammation.

The authors discovered SARS-CoV-2 presence in the nasal mucosa in four patients who experienced chronic loss of smell, even though the virus RNA could not be identified in nasopharyngeal swabs using routine diagnostic RT-qPCR. Because of this surprising discovery, the authors propose that nasal brushing may be used to diagnose SARS-CoV-2 in patients who have lost their sense of smell, in addition to nasopharyngeal swabbing for PCR research.

In chronological order, the analysis showed the step-by-step process of COVID-19-related loss of smell. The cilia on the surface of sensory neurons vanish when they are infected with a virus. Cilia are slender extensions of the cell's bounding membrane that lock onto odorant molecules and are the first step in smelling. The researchers discovered that SARS-CoV-2 can survive in human nasal sensory neurons for several months after the disease symptoms have subsided.

The nasal epithelium is a flattened cell bed with a well-organized structure that allows us to smell. SARS-CoV-2 infection disrupts the nasal epithelium's structure by inducing programmed cell death, according to the authors (apoptosis).

The authors added, "We also discovered that this inflammatory process that occurs in the nasal cavity extends to the olfactory bulb." The first cerebral relay station of the olfactory system is the olfactory bulb. These results are in line with previous research on COVID-19 patients who died with inflammatory signatures such as microgliosis in the olfactory bulb.

SARs-CoV-2 infection of nasal sensory neurons and subsequent infection of the olfactory bulb, according to the authors, serves as a gateway for the virus's entry into more distant parts of the brain, such as the brainstem and cerebral cortex, through a mechanism known as "retrograde invasion."

“The results we obtained are clinically important in the treatment of COVID-19 patients, since olfactory function loss could be regarded as a sensitive sign of recurrent viral infection, and should be considered in-patient management,” the researchers wrote.