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.