Conclusion
Our review has shown that there is already significant evidence which demonstrates an association between OD and the novel coronavirus – COVID-19. It is unclear if this finding is unique to this coronavirus as individual viral phenotypes rarely present in such concentrated large numbers. Classically patients present with persistent symptoms following a viral illness many weeks or months after. The symptomology during the infective phase of the virus has not previously been studied and therefore it is not possible to draw direct comparison between other similar viruses. Walker et al have however demonstrated trends between increasing cases of COVID-19 and the increase in positive novel coronavirus cases that was not mirrored during the previous H1N1 pandemic in 2009 .
Due to the rapid spread of COVID-19 in this pandemic it is understandable that there are a lack of studies using objective measures and rigorous controls. The most common methodologies used were cross-sectional questionnaires and case series. These approaches are at risk of bias and we can only discuss associations as a result. Further research will be required to demonstrate clearer links between OD and COVID-19 going forwards.
In the meta-analysis of studies with cohorts of patients who had a positive PCR test the prevalence of OD was 62%. Both Menni et al and Yan et al compared OD to other associated symptoms seen in COVID-19 such as fever, cough, fatigue, dyspnoea and diarrhoea. They both found that OD was the strongest predictor of a positive PCR result for COVID-19 when compared to the other symptoms when applying their logistic regression analysis . It is worth noting that the current self-isolation advice, released by Public Health England, only applies to people experiencing a new continuous cough and/or a high temperature .
When we looked at patients who had experienced OD during the outbreak there were several studies that demonstrated an increase in the prevalence of loss of smell in their populations when compared to previous estimates . The largest data sets, conducted predominantly in the outpatient setting, by Hopkins and Bagheri et al indicated a female preponderance in their cohorts (73% and 71% respectively). These two studies also demonstrated an average affected age between 30-40. It has been demonstrated that both advanced age and the male sex are risk factors for the severe form of the disease and an increased rate of mortality . It could be that this cohort of patients were not targeted by this study due to the more elderly populations not interacting with web-based surveys or being within the inpatient population due to their disease severity. Moein et al demonstrated in their study of inpatients that OD was a common finding in this population too when they applied objective UPSIT testing to confirmed cases . Further research is needed to identify if the incidence of OD varies between different ages and genders and as such if particular disease phenotypes for COVID-19 can give clinicians prognostic information.
In areas where testing has not been adopted widely tracking of this OD could be vital in identifying hot-spots where population-based management strategies can then be targeted. Tracking OD using mobile-based applications, such as the one developed by Menni et al, will allow real time data tracking for aid models in the prediction of national or regional COVID-19 cases . This approach could lead to specific social distancing measures being implemented in areas where OD is wide-spread and will also help in modelling when these measures could be relaxed as most patients seem to recover their sense of smell following the illness.
Given the growing evidence to support an association between OD and COVID-19 it is paramount that national and international health bodies recognise this association. The World Health Organisation and national public health bodies have not yet accepted this link and as such patients with OD are not self-isolating. We have demonstrated that OD can be the first symptom to arise, and in some cases, may be the only symptom(s) that patients experience. We recommend that people who develop OD during the pandemic should be self-isolating and this guidance should be adopted internationally to prevent transmission.