Introduction
There is already a wealth of anecdotal evidence that suggests that olfactory dysfunction (OD) is an important symptom in patients who have contracted the novel SARS-CoV-2 coronavirus (COVID-19). Initial reports made in newspapers from Germany indicated that as many as two thirds of cases of COVID-19 reported loss of smell whilst in South Korea, 15.3% of patients who have tested positive had perceived disturbance of smell or taste . This is the first worldwide pandemic where reporting of symptoms, aided by social media and telecommunication systems, has been shared so widely. High profile public figures have reported both symptoms which has led to increased interest and widespread interest in the press and the public .
It has previously been demonstrated that the genetically similar SARS-CoV virus can spread via a synapse-connected route to the medullary cardiorespiratory centre. Coronaviral RNA has been identified post mortem concentrated in the brain-stem of human patients during the previous SARS-CoV pandemic, and studies in mice have shown that previously described corona viruses can invade intracranially when administered intranasally indicating that the virus may travel via the olfactory nerves. Helms et al present a series of patients infected during the current COVID-19 outbreak and demonstrate numerous neurological sequelae and abnormalities on cross-sectional imaging of the brain.
Brann et al (in a paper made available prior to peer review) have identified non-neuronal cell types, such as sustentacular and olfactory stem cells as well as horizontal basal cells are the potential target of COVID-19 in the human olfactory epithelium via the ACE2 receptor and the spike protein protease TMPRSS2. This presents three main theories for potential loss of smell in COVID-19. Firstly, a local inflammatory response affecting sensory function, secondly damage to support cells and finally escalating damage to the architectural structure of the entire olfactory epithelium, due to damage to sustentacular cells and Bowman’s glands .
Viral upper respiratory tract infection (URTI) is one of the known major identifiable causes of olfactory dysfunction (OD) due to the degeneration of olfactory epithelium . Due to the widespread and insidious nature of viral URTI there is no data relating to the incidence of post-viral OD for specific viruses but post-viral cases typically account for 11% of all cases of OD in the community with cases presenting to specialist clinics typically representing 20% of cases . This group is often represented as a higher proportion in online surveys and patient fora at around 30% . Patients often present to the Otolaryngologist in persistent cases but those that resolve soon after the infective process has subsided are likely rarely reviewed or reported .
BMJ best practice have recently published an update on Coronavirus and the range of symptoms that are associated with this. They quote the anecdotal evidence published by ENT UK and the American Academy of Otolaryngology regarding the link between anosmia and coronavirus. Both these international bodies have both recommended self-isolation for patients who develop these symptoms . Despite lobbying by these representative bodies OD has not been incorporated in to national or international public health policy.
The aim of this systematic review and metanalysis is to identify the currently available evidence for the relationship between COVID 19 and self-reported loss of smell. This will include assessing the potential for OD as a diagnostic marker in COVID-19, outlining the current peer-reviewed evidence relating to this relationship and how it can be utilised going forwards in clinical practice.
We decided to focus on OD and not include loss of taste in this review. OD will lead to reduced retronasal olfaction and subsequently impact the perception of taste in these patients. Flavour perception involves input from ortho and retronasal olfaction and gustation, complemented by trigeminal stimulation through touch and pain fibres. Patients typically find it difficult to isolate true gustatory sensations from retronasal olfaction without objective gustatory testing . Given the difficulties in interpreting this symptom, in the absence of more detailed questions regarding taste perception, we decided to solely review OD.