Smell, taste dysfunction post-COVID-19: will these persist?

Olfactory and gustatory** loss/alterations are common COVID-19 symptoms, but recovery is expected in most patients within the first 3 months. However, these dysfunctions may persist in some individuals, according to a reconstructed meta-analysis from Singapore.

“[P]ersistent smell and taste dysfunction could be considered a focal neurologic deficit and can have an impact on quality of life and general health long after recovery from COVID-19,” said the researchers. “Considering the potentially serious sequelae associated with [these] dysfunctions, and the need for doctors to counsel patients on their anticipated recovery course, it is essential to investigate the burden of persistent symptoms and identify relevant prognostic factors.”

In this meta-analysis (n=3,699 [18 studies]), three-quarters of participants have recovered their senses of smell (74 percent) and taste (79 percent) at 30 days. These continued to improve that by day 180, almost all have achieved recovery (96 percent [smell] and 98 percent [taste]). [BMJ 2022;378:e069503]

Based on parametric cure modelling, persistent self-reported smell and taste dysfunction could develop in an estimated 5.6 percent and 4.4 percent of patients with initial dysfunction, respectively. [BMJ 2022;378:o1939]

These figures may appear nominal but considering that more than half a billion people across the globe have contracted COVID-19 as of July 2022, these estimates translate to >15 million people with continued olfactory dysfunction, while >12 million individuals have been left with a persistent gustatory disorder. [ACS Chem Neurosci 2020;11:2944-2961] “This outcome might contribute to the growing burden of long COVID,” they said.

What is more, self-reporting may have overestimated recovery, implying that the real burden of olfactory dysfunction may be even greater. [BMJ 2022;378:o1895]

Underlying mechanisms

The delayed smell recovery may be ascribed to the varying speeds by which support cells and sensory neurons regenerate owing to varying degrees of inflammation, the researchers noted. “Stem cell damage and severe inflammation may also prolong smell dysfunction by slowing the regeneration of the olfactory [epithelium].”

For the delayed taste recovery, the binding of SARS-CoV-2 to ACE2** receptors in the salivary glands may impair salivary flow, triggering ‘conductive’ taste dysfunction. [Int J Oral Sci 2020;12:8] “Viral binding with oral mucosal cells might trigger inflammation, abnormal cell turnover, and reduced tastebud sensitivity and thus sensorineural taste dysfunction, which may have varying regeneration speeds,” they said.

Poorer recovery in women

Recovery of these senses were also less likely in women than in men (odds ratio [OR], 0.52 [smell] and OR, 0.31 [taste]). “One reason could be the better baseline olfaction and gustation in [women], which may result in greater sensitivity to changes and a larger subjective impairment,” the researchers said.

Another possible mechanism is the upregulation of ACE2 expression by oestrogen. [Biol Sex Differ 2020;11:29] “[T]he ACE2 receptor … may have higher expression in women, or may express heterodimers that alter virus binding, thus potentially enhancing viral invasion in women,” they added.

Unanswered questions

Further studies are warranted to shed light on why women are particularly affected, and to determine if there are methods that patients can do to hasten recovery. Whether the sensory loss would be permanent or olfactory training may improve outcomes have yet to be ascertained.

“These are important questions … that need to be taken seriously and investigated by the medical and research community,” the researchers stressed.

“Even as we learn to cope with living in the era of the COVID-19 pandemic, we must keep in mind that COVID-19 is not merely a simple cough and cold but may have far-reaching and long-lasting consequences,” they said. “Persistent smell and taste loss is only one of the many health issues in the disease spectrum of long COVID, and it remains clear that more can and must be done for these patients.”