Discussion
This study provides data about the use of saliva for the detection of
SARS-CoV-2 specific antibodies of samples from COVID-19 patients. The
present study was conducted at The Third People’s Hospital of Shenzhen
in September 2020, so most patients enrolled were in the recovery phase
of the disease. This may explain why the percentage of positive rate of
SARS-CoV-2 nucleic acid in our inpatients series was low.
Saliva has been used over decades for evaluating human health. It offers
several advantages as a diagnostic medium in that it is a noninvasive,
painless, safe, and convenient specimen. Whereas some consider
phlebotomy specimens to be too invasive and uncomfortable, saliva
sampling is widely accepted, particularly among vulnerable or
difficult-to-reach populations, and could facilitate home-based
self-collection [12,13]. Pisanic N et al. have tested SARS-CoV-2
specific IgA, IgG and IgM in saliva specimens with considerable
detection rate [8]. In an Australian family case, saliva antibodies
were also detected from all family members [14]. In our study,
despite the low detection rate, IgA, IgG and IgM were all detectable in
saliva specimens.
Secretory IgA is a principal component of mucosal immunity, and can
easily be measured in saliva[15]. In a recent research, IgA has been
proved to be the dominant antibody in early SARS-CoV-2-specific humoral
responses [16]. Salivary IgA antibody response was reported to be
particularly prevalent in younger individuals with mild SARS-CoV-2
infection [17]. Similarly, in our results, the level and detection
rate of IgA in saliva were obviously higher than IgG and IgM. The
correlation between saliva and serum SARS-CoV-2-specific antibodies has
been assessed that IgA, IgG and IgM levels in matched saliva and serum
samples were all significantly correlated [8]. While, IgA levels in
the saliva was reported to exhibit the poorest correlation with IgA
levels in the serum[18]. In our results, levels of IgG and IgM in
saliva were obviously lower than in serum. When comparing the IgA level
in paired saliva and serum samples, no clear correlation could be drawn.
Recently, saliva has been proposed as a suitable specimen for the
diagnosis of COVID-19, and the collection method would reduce the
exposure risk of frontline health workers which is one of major concerns
in primary healthcare settings [19]. SARS-CoV-2 RNA could remain
detectable in saliva over a 1-week period but the test is unstable and
vulnerable [20,21]. Neutralizing IgA was reported to remain
detectable in saliva for a longer time (days 49 to 73 post symptoms)
than in serum [16]. Our results have shown that testing for
antibodies against SARS-CoV-2 was sensitive in saliva samples, providing
an easy, noninvasive option for detection of prior infection. The
combination of antibody test on saliva and traditional molecular assays
on nasopharyngeal swabs could approve the diagnosis ability. Also, the
increased salivary IgA has been proposed to serve as a biomarker to
identify patients at an elevated risk of clinical deterioration in
COVID-19 [15]. All these evidences suggested that the IgA in saliva
could play an important role in COVID-19 diagnosis.
This study has several limitations. First, it is well known that the
antibody concentration in human saliva is orders of magnitude lower than
in blood or serum. Assays with exquisite analytical sensitivity and
capable of detecting high signal over background noise were demanded
[22]. Additionally, our sample set was not large enough, especially
lacking the samples at early time points, weakening the robustness of
our findings in saliva. Future studies could improve on the robustness
by including a larger sample size at all time points.