Long-lasting smell or taste dysfunction may affect about 27 million people globally who have had SARS-CoV-2 infection, a meta-analysis with parametric cure modeling showed.

An estimated 5.6% and 4.4% of COVID-19 patients may develop persistent self-reported smell and taste dysfunction, respectively, representing 15 million and 12 million cases worldwide as of July 2022, reported Song Tar Toh, MBBS, of the National University of Singapore, and colleagues.

Women were less likely to recover their sense of smell or taste, they wrote in The BMJ. COVID patients with greater initial severity of dysfunction and patients with nasal congestion were less likely to recover their sense of smell.

Changes in smell and taste are highly prevalent in patients with COVID-19, with 40%-50% of people on average reporting these symptoms globally, the researchers said.

Loss of smell and taste can lead to poorer quality of life and may contribute to the rising burden of long COVID, Toh noted.

“Even though there were many people affected worldwide pre-pandemic, many do not have access to help or know help is available,” he told MedPage Today. “The pandemic brought forth this important medical problem to the attention of physicians and patients.”

Health systems may be unprepared for the scale of this challenge, observed Paolo Boscolo-Rizzo, MD, of the University of Trieste in Italy, and colleagues in an accompanying editorial.

“Health leaders, policymakers, and research funders should realize the extraordinary importance of good chemosensory function for the well-being of humans, allocate adequate resources to support chemosensory research, and sustain medical specialists faced with an exceptional number of patients with smell and taste dysfunction,” they wrote.

Few evidence-based options exist to treat chemosensory disorders, the editorialists pointed out. “Olfactory training, started as soon as possible after the onset of symptoms, is the only disease-specific intervention with evidence of efficacy for the treatment of post-infectious olfactory dysfunction,” they noted.

Mechanisms of COVID-induced olfactory loss are unknown, but could provide a more solid basis for the development of new treatment strategies, Boscolo-Rizzo and colleagues added.

“Although the involvement of olfactory bulb and central olfactory pathways cannot be excluded, most evidence points to the virus targeting supporting cells of the olfactory neuroepithelium,” they wrote. “These cells — not olfactory neurons — express the molecular make-up necessary for entry of the virus.”

Toh’s group analyzed 18 observational studies of adults with COVID-related changes to smell or taste and included 3,699 patients in their meta-analysis. Four studies were conducted in community settings and 14 were in hospital settings. Risk of bias was low to moderate and evidence quality was moderate to high.

The researchers used cure modeling to estimate self-reported rates of smell and taste recovery and identify key factors associated with the duration and likelihood of recovery. Modeling projected that persistent self-reported smell dysfunction could develop in an estimated 5.6% (95% CI 2.7%-11.0%) of patients and taste dysfunction could develop in 4.4% (95% CI 1.2%-14.6%). Sensitivity analyses suggested these could be underestimates.

Reconstructed time-to-event patient data showed recovery rates increased over time. At 30, 60, 90, and 180 days, about 74%, 86%, 90%, and 96% of patients reported smell recovery and 79%, 88%, 90%, and 98% reported taste recovery, respectively. SARS-CoV-2 variants were not reported with respect to smell or taste recovery.

Women were less likely to recover their sense of smell (OR 0.52) or taste (OR 0.31) than men. Patients with greater initial severity of dysfunction (OR 0.48) or nasal congestion (0.42) were less likely to recover their sense of smell.

The researchers acknowledged several limitations in their analysis. Studies varied in quality and smell and taste dysfunction was based on self-reported data. Self-reports may overestimate recovery, suggesting that the true burden of olfactory dysfunction is even greater, Toh and colleagues noted.

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