RR:C19 Evidence Scale rating by reviewer:
Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.
The investigators use an olfactometer – an instrument designed to deliver odorants to human subjects at a fixed concentration – to measure the olfactory ability of healthy people versus those who are currently infected by COVID-19 (as measured by a nasal swab test). The results of this research adds to our knowledge of COVID-19 biology by pointing out that while most subjective reports of smell loss indicate that loss of smell is nearly complete (anosmia; inability to smell), here we learn that for people who are infected but without other symptoms, the smell loss, while detectable, can be partial rather than total. Many studies to date have studied smell loss in COVID-19 patients1-92 but to the best of my knowledge and as I write this review as of Sept 4th 2020, none have used as accurate and as sensitive methods to measure smell as reported here.
Several features of the research procedures merit should be highlighted. First, the concentration of odorants delivered were measured by photoionization detector which is helpful to rule out the technical explanation that person-to-person differences in the ability to detect an odorant are due to the vicissitudes of odorant concentration, which can arise when cruder methods are used, e.g., scratch-and-sniff. To date and to the best of my knowledge, there are12 studies that use objective tests to assess smell in patients with COVID-19, but here the odorant concentration is measured and controlled by the use of an olfactometer. Another useful aspect of the methods here are that the investigators used ten odorants and so the overall assessment of the patient is more complete than studies using single or fewer odorants. The reason this point is important is that the genotype of human olfactory receptors is exceptionally variable and therefore a person might be unable to detect a particular odor not because they have COVID-19, but because they have a specific blindness that that odorant (specific anosmia). Most of the commonly used odorant tests select odors that are sensed by most people but the small possibility of specific anosmia remains. Using ten odorants as the investigators have done here circumvents this issue.
The main finding of interest was that whereas the participants who had COVID-19 were mostly unaware that they had smell deficits which reinforces the point that objective tests of olfactory function are needed for COVID-19 surveillance. And two final points require highlighting: the authors provided as supplemental data an informative video explaining the equipment, they used to test the participants and they presented practical information about how the instrument was decontaminated which is salient during the pandemic when sanitation is part of human subject protections.
There were limitations to this study, the most salient being the lack of test-re-test measures; ideally, we would like to observe how reproducible the results would be for a specific subject when tested again, e.g., in a few hours or within a day. Another issue was the potential to introduce differences in the olfactometer measures that might arise from moving the instrument, e.g., from the laboratory to the quarantine location. More details about the standardization procedures would have strengthened the manuscript.
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