A groundbreaking synthesis of data provides new insight into COVID-19-related smell and taste dysfunction.

While smell and taste dysfunction are highly prevalent in patients with COVID-19, little is known about the path to recovery, including what percentage of patients succeed in regaining these senses long-term.

Prior to the COVID-19 pandemic, these functional levels were not top-of-mind for most clinicians, said Naweed Chowdhury, M.D., M.P.H., an associate professor of otolaryngology-head and neck surgery at Vanderbilt University Medical Center.

However, the pandemic brought the issue to the forefront for many. Now, Chowdhury and his team are examining how those affected might fare as time goes on.

“During the pandemic, we didn’t know whether COVID-19-related chemosensory dysfunction was transient or permanent, so we conducted a systematic review and meta-analysis to help answer this question,” he said.

Chowdhury, along with 18 other researchers, conducted a study, with findings published in the British Medical Journal. The cohort of 3,699 patients was among the largest to date examining COVID-19 patient data related to smell and taste.

The findings help identify prognostic factors associated with smell and taste recovery that may guide physicians in providing better support and treatment.

Quantifying Sensory Loss

The analysis included patients enrolled in 18 studies. Using parametric cure modelling, the researchers determined that persistent self-reported smell and taste dysfunction would likely develop in 5.6 percent and 4.4 percent of patients, respectively, representing about 27 million patients worldwide.

Chowdhury noted that these numbers could be underestimates, given that proportions of patients with persistent smell and taste dysfunction has been logged as 6.6 and 8.2 percent, respectively, in other studies.

“Women were less likely to recover their sense of smell and taste, and patients with greater initial severity of dysfunction and those with nasal congestion were less likely to recover their sense of smell,” Chowdhury said. These findings were consistent with other studies that explored persistent dysfunction at long follow-up durations.

Mechanics of Dysfunction

Although the specific underlying mechanisms of COVID-19-related olfactory dysfunction remain poorly understood, Chowdhury hypothesized that sensori-neural mechanisms are mainly responsible, noting that sensori-neural interference can block sensory receptor function or impede signal transmission to the brain.

“SARS-CoV-2 infects and eliminates most olfactory epithelial sustentacular cells that express angiotensin converting enzyme-2, which leads to olfactory neuron deciliation and necrosis,” he explained. “Varying regeneration speed of sustentacular cells and sensory neurons, influenced by the degree of inflammation, could explain the delayed smell recovery.”

Regarding prognostic factors, Chowdhury expects that a higher initial severity of smell dysfunction may lead to an extended recovery. He notes that it is not clear why female sex is associated with poorer recovery, though this finding is consistent with previous reports of post-viral smell dysfunction.

Future Directions

Previous work has shown that recovery of these senses is possible, even after many years, Chowdhury said. Thus, he recommends that subjects be followed on a long-term basis following COVID-19.

Additional studies are needed to confirm the findings and to investigate appropriate treatment options, he said. While knowledge-based treatment options are limited, new evidence suggests a potential role for platelet-rich plasma injected into the olfactory region as a potential avenue.

“Before, post-viral olfactory dysfunction was considered rare and had very little support,” Chowdhury said. “Now, with new drugs targeted at these areas of pathophysiology that have been described, we hope to move faster in developing effective treatments.”


Naweed Chowdhury, M.D.

Naweed Chowdhury, M.D., is an associate professor of otolaryngology-head and neck surgery at Vanderbilt University Medical Center. His areas of clinical specialty include nose and sinus conditions and skull base surgery.