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.