Persisting Salivary IgG against SARS-CoV-2 at 9 Months After Mild COVID-19: A Complementary Approach to Population Surveys

Abstract

Background: Declining humoral immunity in COVID-19 patients and possibility of reinfections has raised concern. Mucosal immunity particularly salivary antibodies could be short-lived. However, long-term studies are sparse. Methods: Using a multiplex bead-based array platform, we investigated antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins in 256 saliva samples from convalescent patients 1-9 months after symptomatic COVID-19 (n=74, Cohort 1), undiagnosed individuals with self-reported questionnaires (n=147, Cohort 2), and individuals sampled pre-pandemic time (n= 35, Cohort 3). Results: Salivary IgG antibody responses in Cohort 1 (mainly mild COVID-19) were detectable up to 9 month recovery, with high correlations between spike and nucleocapsid specificity. At 9 months, IgG remained in saliva in majority as seen in blood serology. Salivary IgA was rarely detected at this timepoint. In Cohort 2, salivary IgG and IgA responses were significantly associated with recent history of COVID-19 like symptoms. Salivary IgG also tolerated temperature and detergent pre-treatments. Conclusions: Unlike SARS-CoV-2 salivary IgA that appeared short-lived, the specific IgG in saliva appears stable even after mild COVID-19 as noted for blood serology. The non-invasive saliva-based SARS-Cov-2 antibody testing with self-collection at homes may thus serve as a complementary alternative to conventional blood serology.

Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG

“…Similarly, data from previous cross-sectional studies showed detectable SARS-CoV-2 -specific IgA and IgG levels in saliva 2-4 weeks after onset of symptoms, with only IgG response antibodies persisting beyond 60 days [8,9]. A different study reporting results from single saliva samples collected <3 to 9 months after onset of disease showed a consistently high IgG positivity, but a significant decrease of IgA [10]. In a longitudinal study including 95 participants, the mean time from disease onset to IgG detection in saliva was 9-11 days and IgG antibodies remained detectable until day 90 [19].…”

“…The sensitivity of both assays was high (IgA: 95.5%; IgG: 89.7%) without compromising specificity (IgA: 99%; IgG: 97%). Other published studies have shown high sensitivity for IgG (88-98.4%), but low (17-59%) for IgA, with a high specificity for both isotypes (96-100%) [8][9][10][11]. Difference in sensitivity between our and other IgA assays could be explained by the assay platform, type of sample, or collection time after infection.…”

“…At mucosal membranes, IgA is the main immunoglobulin class and is found most often in the secretory form (sIgA). Within 2-3 weeks after onset of disease, SARS-CoV-2-specific IgG antibodies can be detected in saliva, persist for at least 9 months, and show high correlation with serum antibody levels in most COVID-19 patients [8][9][10][11]. Salivary IgA antibodies, on the contrary, rapidly increase 1 week after onset of disease, become undetectable 4-5 weeks later, and show a moderate correlation with serum levels [8,9].…”

Prevalence, Distribution and IgG Antibody Levels Associated with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Among Health-System and Community-Based Employees and Patients

“… 13 , 21 Newer studies in Sweden show that the antibodies against SARS-COV-2 are detectable 9 months after the infection. 22 The strong immune response after a natural infection with SARS-COV-2 is also supported by the low incidence of breakthrough infections among seropositive compared to seronegative individuals across various age groups. 23 , 24 For example, in large cohort in England (n=2,111), seropositive individuals tested at least monthly were 41-85% less likely to have a positive PCR test for SARS-COV-2 when compared to seronegative individuals.…”

Appearance of IgG to SARS-CoV-2 in saliva effectively indicates seroconversion in mRNA vaccinated immunocompromised individuals

“…Antibodies binding to the full-length spike glycoprotein in trimeric form (Spike-f) and the S1 subunit were measured by means of a multiplex bead-based assay in the 384-well plate format (38, 39) as previously described. Briefly, the antigens were immobilized on the surface of uniquely color-coded bead identities (IDs) (MagPlex-C, Luminex corp.), and the IDs pooled to generate the bead-array.…”