Diagnostic potential of saliva for SARS-CoV-2
It has been reported that the angiotensin converting enzyme II (ACE2) is
the host cell receptor to which the SARS-CoV-2 binds to gain entry into
cells, same as SARS-CoV.9,17 Xu et al have
demonstrated that the receptor binding domain of SARS-CoV-2 spike
protein supports strong interactions with the human ACE2
receptor.18 The ACE2 protein is present in most organs
of the human body, and is abundantly expressed in the vascular
endothelial cells, heart, alveolar epithelial cells of lungs and
enterocytes of the intestine.19 These findings
indicate that these organs may potentially be at high risk for COVID-19
infection.20 Recently, RNA sequencing studies from The
Cancer Genome Atlas database have identified that there is a high
expression of the ACE2 receptors on the epithelial cells of oral
mucosa.21 Among oral sites, the highest expression was
seen in the epithelial cells of tongue, followed by buccal and gingival
tissues. These findings may provide clues for further investigation of
oral routes of infection, pathogenesis and detection of COVID-19.
Previous studies have demonstrated that salivary specimens have a higher
than 90% concordance rate with nasopharyngeal specimens in the
detection of respiratory viruses.22 In an initial
pilot study by To et al.,23 SARS-CoV-2 was detected in
the salivary specimens of 11 out of 12 patients with
laboratory-confirmed COVID-19, and all 33 individuals who tested
negative for nasopharyngeal specimens also tested negative for salivary
specimens. In another recently published study, posterior oropharyngeal
saliva samples were collected for 23 patients with laboratory-confirmed
COVID-19 for nasopharyngeal specimens.24 Of these, 20
patients (87%) tested positive for SARS-CoV-2 in their saliva. Serial
viral load was ascertained using reverse transcriptase quantitative
polymerase chain reaction (RT-qPCR). It was found that the salivary
viral load was highest during the first week after symptom onset and it
declined over time. The salivary sample was self-collected by patients
by coughing up saliva from the posterior oropharynx. Therefore it is
possible that these specimens included secretions from the nasopharynx
or the lower respiratory tract, rather than being completely salivary.
In a study by Williams et al.,25 622 individuals were
tested for COVID-19 using nasopharyngeal specimens, of which 522 also
provided salivary specimens. For salivary specimen collection, they were
instructed to pool saliva in their mouth for 1-2 minutes, and gently
spit into a collection pot. 33 of the 39 patients (84.6%) who tested
positive for nasopharyngeal specimens, also had SARS-CoV-2 detected in
their saliva.25 A study of 44 COVID-19 inpatients
noted a high correlation between nasopharyngeal and salivary samples,
with higher viral titers in saliva.26 It was found
that the salivary specimens yielded higher detection sensitivity and
consistency throughout the course of disease. This study also enrolled
98 asymptomatic healthcare workers, who self-collected nasopharyngeal
and salivary specimens every three days for a period of two weeks.
SARS-CoV-2 was detected in saliva from two healthcare workers who tested
negative for matching nasopharyngeal samples.26 These
data, although limited, suggest that saliva may be more sensitive in
detection of asymptomatic or pre-symptomatic infections.
Researchers from Rutgers University evaluated the use of salivary
specimens for SARS-CoV-2 detection in symptomatic patients from three
ambulatory care centers.27 They found 100% positive
and negative concordance between results obtained from testing of saliva
and those obtained from nasopharyngeal and oropharyngeal swabs [saliva
vs nasopharyngeal swab: (26/26) positive agreement, (27/27) negative
agreement; saliva vs oropharyngeal swab: (4/4) positive agreement, (3/3)
negative agreement]. The U.S. Food and Drug Administration (FDA) has
since issued them an emergency use authorization for the use of salivary
specimens, in addition to the nasopharyngeal and oropharyngeal swabs,
for detection of SARS-CoV-2 RNA in individuals suspected of
COVID-19.27 A salivary diagnostic test would allow for
a noninvasive self-administered sample collection under healthcare
providers’ directive for individuals in quarantine, and would circumvent
the issues regarding global shortage of swabs and personal protective
equipment (PPE) needed for conventional COVID-19 testing. Specific
guidelines are needed to standardize the method for collection of
salivary specimens, and implement the use of appropriate assays, and
processing methods. The presence of SARS-CoV-2 in the saliva of infected
patients also bears implications for a high potential of transmission in
the dental operatory, and underscores the need for awareness and use of
effective PPE practices.