Frequency and Clinical Utility of Olfactory Dysfunction in COVID-19: a Systematic Review and Meta-analysis

Olfactory dysfunction (OD) has been gaining recognition as a symptom of COVID-19, but its clinical utility has not been well defined.

To quantify the clinical utility of identifying OD in the diagnosis of COVID-19 and determine an estimate of the frequency of OD amongst these patients.

PubMed was searched up to 1 August 2020. Meta-analysis A included studies if they compared the frequency of OD in COVID-19 positive patients (proven by reverse transcription polymerase chain reaction) to COVID-19 negative controls. Meta-analysis B included studies if they described the frequency of OD in COVID-19 positive patients and if OD symptoms were explicitly asked in questionnaires or interviews or if smell tests were performed.

The pooled frequency of OD in COVID-19 positive patients (17,401 patients, 60 studies) was 0.56 (0.47-0.64) but differs between detection via smell testing (0.76 [0.51-0.91]) and survey/questionnaire report (0.53 [0.45-0.62]), although not reaching statistical significance (p = 0.089). Patients with reported OD were more likely to test positive for COVID-19 (diagnostic odds ratio 11.5 [8.01-16.5], sensitivity 0.48 (0.40 to 0.56), specificity 0.93 (0.90 to 0.96), positive likelihood ratio 6.10 (4.47-8.32) and negative likelihood ratio 0.58 (0.52-0.64)). There was significant heterogeneity amongst studies with possible publication bias.

Frequency of OD in COVID-19 differs greatly across studies. Nevertheless, patients with reported OD were significantly more likely to test positive for COVID-19. Patient-reported OD is a highly specific symptom of COVID-19 which should be included as part of the pre-test screening of suspect patients.