Immune system-triggered inflammation is the likely reason for the loss of smell reported by many COVID-19 patients, a new study finds.

"As a neuropathologist, I wondered why smell loss is a very common symptom with COVID-19 but not with other respiratory diseases," said lead study author Dr. Cheng-Ying Ho. She is an associate professor of pathology at Johns Hopkins University School of Medicine in Baltimore.

"So, we decided to dig deeply into the mechanics of smell to see what actually occurs at the cellular level when SARS-CoV-2 invades the body," Ho said.

For the study, her team analyzed tissue from the olfactory bulb in 37 people who died of various causes. Located at the base of the brain, the olfactory bulb transmits nerve impulses carrying information about odors.

The tissue came from 23 people who died of COVID-19 and a control group of 14 people who had no detectable SARS-CoV-2 at the time of their deaths.

Three of the 23 COVID-19 patients had lost their sense of smell; four had diminished ability to smell; and two lost both smell and taste. None of the 14 patients in the control group had lost either smell or taste.

"When we compared the tissues from patients without COVID-19 with those from persons who had been infected with SARS-CoV-2 — especially the ones with diminished or complete loss of smell — we found that the group with COVID showed more severe vascular injury and far fewer axons [nerve fibers brain cells use to transmit signals] in the olfactory bulb," Ho said in a university news release.

She noted that this didn't change when researchers adjusted for the impact of age, "strongly suggesting that these effects aren't age related and therefore, are linked to SARS-CoV-2 infection."

The researchers were surprised to find that despite nerve and vascular damage, SARS-CoV-2 particles were not detected in the olfactory bulb in a majority of COVID-19 patients.

"Previous investigations that only relied on routine pathological examinations of tissue — and not the in-depth and ultrafine analyses we conducted — surmised that viral infection of the olfactory neurons and olfactory bulb might play a role in loss of smell associated with COVID-19," Ho said.

She said the new findings suggest that SARS-CoV-2 infection of membranes lining the nose leads to inflammation, which in turn damages neurons, reduces the numbers of axons available to signal the brain, and renders the olfactory bulb dysfunctional.

The findings were published online April 11 in JAMA Neurology.

The next step is to analyze tissues from patients who died of the delta and omicron variants of COVID-19, the researchers said.

"We want to compare any axon damage and bulb dysfunction found in those tissues with what we observed in patients who had the original virus strain," Ho said. "That way, we'll be able to better predict if delta and omicron are more or less likely to cause loss of smell."