Anosmia (loss of smell) confirmed as a clinical feature of COVID-19

By Dr. Liji Thomas, MDApr 15 2020

Earlier last month, the association of ear, nose, and throat (ENT) specialists in the UK issued a public statement advising patients with a sudden loss of smell or taste to get tested for COVID-19. They cited not only their own observations but those from numerous other ENT consultants the world around. A review of multiple papers on the sinus and nasal symptoms and signs related to the diagnosis of COVID-19, published in April 2020, in the journal Laryngoscope Investigative Otolaryngology, reiterates this finding.

In his study, Dr. Ahmad Sedaghat, an ENT physician from the University of Cincinnati, confirms that anosmia, the loss of smell, is a key sign of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. Even in patients who show no other sign of illness, anosmia could indicate the presence of the virus, according to these sources.

How does the virus enter the body cells?

Infection by SARS-CoV-2 depends on the S1 spike glycoprotein on the envelope for attachment to the host cell. It also requires two host proteins, the angiotensin-converting enzyme 2 (ACE2), which is the receptor on the cell surface, binding to the spike protein, and triggering endocytosis, whereby the virus enters the cell.

SARS-CoV-2 viruses binding to ACE-2 receptors on a human cell, the initial stage of COVID-19 infection, conceptual 3D illustration credit: Kateryna Kon / Shutterstock By

The second is called transmembrane protease serine 2 (TMPRSS2), an enzyme in the endosomal compartment that splits the S1 spike protein. The result is the fusion of the virus envelope with the endosomal membrane and the insertion of the viral genetic material and other components into the host cytoplasm. The virus then replicates itself, and the host cell releases the new viral particles to infect other cells.

The level of expression of the TMPRSS2 gene in the nasal mucosa is influenced by factors like atopy, or air pollution. This may explain why the disease manifestations vary between countries and individuals.

The importance of the nasal and sinus cavities in COVID-19

It is likely that most infections with the virus enter the body through the nose since this is how 90% of inhaled air enters the lungs. The nasal lining cells may have genes that increase the susceptibility of the cell to the virus. Environmental and host factors are also important. The high degree of viral shedding from the nose makes ENT procedures an area of very high risk of contagion for healthcare professionals.

In such patients, the virus replicates within the lining cells of the nasal mucosa. The viral particles released from these cells through mucus are able to infect more cells as well as to leave the body via aerosols. These aerosolized droplets are formed during sneezing or coughing and spread outwards to infect anyone who breathes the same air potentially.

If an infected person with such a mucoid discharge were to touch their noses, for instance, to wipe the nose and then don’t wash the hands before touching another surface, the latter could be contaminated. This can serve as a source of infection.

How is the diagnosis made at present?

The diagnosis of COVID-19 is typically made when individuals who may have been exposed to the virus develop fever, cough, and a feeling of breathlessness. If they also then develop severe breathing distress, feel constant pressure or pain in the chest, become confused (not fully aware of the surroundings), or are difficult to rouse to full consciousness, severe or critical illness is diagnosed. Medical assistance should be sought at once.

In up to 80% of cases, the disease is thought to be asymptomatic or mild and resolves by itself without medical support.

Anosmia and COVID-19

The olfactory epithelium is a 150 square cm area of smell-sensitive neurons located above the respiratory mucosa of the nasal cavity. It is, therefore, readily infected by the virus, resulting in the loss of smell.

The current review covered 19 papers reporting various disorders of the nose and sinuses observed concerning the current pandemic of COVID-19. One of them is a Paris study of 55 patients who presented with anosmia but had no nasal block and were tested for the virus by nasal swabs. The polymerase chain reaction (PCR) was used to test for the presence of the virus. The study showed that 94% of them had COVID-19.

The authors of the unpublished Parisian paper, Dominique Salmon and Alain Corré, described their findings: “Patients with allergic rhinitis seem more affected. It occurs suddenly 2 to 3 days after the beginning of usually rather mild symptoms related to COVID 19 disease such as headaches, low-grade fever, and diarrhea. In most cases, the signs of cold (such as cough, fever) are absent or have disappeared.” The sense of smell usually begins to return within 5-10 days but may take longer to recover in some patients completely.

What does this mean for clinicians and patients?

The critical indicator that the anosmia is related to the virus is the absence of other symptoms of a viral cold or the seasonal flu, like nasal obstruction, or the production of excessive mucus. The anosmia may occur at any time, but if it is the first symptom, it is still more important as it could help to recognize the illness early and prompt self-isolation to limit its spread.

This motivated the current call to recognize sudden-onset anosmia without other symptoms of nasal involvement as a sign of COVID-19, and restrict one’s social activity, isolate from others at home and work, and ask healthcare providers about testing. This comes against a background of uncertainty as to when a patient should be tested for the illness since the testing capability is limited, and the increase in the number of suspected cases is huge.

When coupled with high levels of viral replication within the nasal mucosa, the early occurrence of this sign and the fact that the patient has no or very mild symptoms of infection, the presence of anosmia should prompt an early call for testing and self-quarantine.

Says Sedaghat, “The occurrence of sudden onset anosmia without nasal obstruction is highly predictive of COVID-19 and should trigger the individual to immediately self-quarantine with presumptive COVID-19.”