key: cord-266232-2ctfmjb8
authors: Trubiano, Jason A; Vogrin, Sara; Kwong, Jason C; Holmes, Natasha E
title: Alterations in smell or taste – Classic COVID-19?
date: 2020-05-28
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa655
sha: 
doc_id: 266232
cord_uid: 2ctfmjb8

nan

A c c e p t e d M a n u s c r i p t Dear Editor, There are increased reports of loss of smell (anosmia) and taste (ageusia) in patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 , in particular in the setting of mild disease. The data to date has been presented predominantly from post-diagnosis surveys or retrospective cohort series [1] [2] [3] [4] [5] . The pathogenesis is postulated to be due to invasion of the olfactory neuroepithilium and olfactory bulb, seen previously in other coronaviruses, due to the high expression of angiotension-converting enzyme (the receptor which allows virus cellular entry) present in the respiratory system [1, 6] . Luers and colleagues described from a retrospective adult cohort of confirmed SARS-CoV-2 from Germany (n = 72) that 74% of patients reported anosmia and 69% ageusia [7] . Spinato et al. prior to this also described from a retrospective cohort study of COVID-19 patients interviewed 5-6 days post diagnosis that 64.4% reported alternations in taste or smell [1] . However, both these studies suffer from the absence of a control group and significant limitation of recall and selection bias. testing (eTable 1). The distribution of symptom prevalence over time is displayed in eFigure 1. In those who underwent SARS-CoV-2 testing, anosmia or ageusia were more frequently reported in females and in those reporting more symptoms (eTable1). Of those who reported anosmia or ageusia, 9.3% tested positive for COVID-19 (positive predictive value), while the negative predictive value was 98.5%. Ansomia and/or ageusia were more common in COVID-19 positive than negative (39.3%

A c c e p t e d M a n u s c r i p t vs 8.9%, p <0.001), and were more common when examined in isolation: anosmia (25% vs 5%, p <0.001) or ageusia (25% vs 6%, p = 0.002) ( Table 1) . After adjusting for confounders, both anosmia and ageusia were independently associated with SARS-CoV-2 infection, eTable 2.

Whilst supporting the observations made by Leuers [7] and Spinato [1] , our data also highlights a significantly lower prevalence of symptoms in a comparative outpatient COVID-19 population (39.3% [AUS] versus 64.4% [US] versus 68% [Germany]) when prospective data is used. Also, we demonstrate similar olfactory symptoms in the control group (SARS-CoV-2 negative). It is important for clinicians to realize that ansomia and ageusia are likely to be commonly reported symptoms in other upper respiratory tract infections, when appropriately asked (8.9% of our COVID-19 test negative group) [3, 8] . From data available, anosmia and/or ageusia whilst associated with COVID-19

should not yet be considered pathognomonic for the disease. Larger prospective population studies are required to validate these findings, as we collectively search for key clinical predictors of COVID-19 that can aid clinical decision making.

A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t

Alterations in Smell or Taste in Mildly Symptomatic Outpatients With SARS-CoV-2 Infection

Self-reported olfactory loss associates with outpatient clinical course in Covid-19

Acute-onset smell and taste disorders in the context of Covid-19: a pilot multicenter PCR-based case-control study

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Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study

Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43

Olfactory and Gustatory Dysfunction in Coronavirus Disease 19 (COVID-19)

Characteristics of olfactory disorders in relation to major causes of olfactory loss

SPO2, median (IQR) 98 (97, 99) 98 (97, 99) 98

Temperature Tympanic, median (IQR)

Systolic Blood Pressure, median (IQR)

Diastolic Blood Pressure, median (IQR)

Respiratory Rate, median (IQR) 18

Pulse Rate, median (IQR)

A c c e p t e d M a n u s c r i p t