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

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