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BackgroundImmunocompromised individuals are highly susceptible to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Whether vaccine-induced immunity in these individuals involves the oral cavity, a primary site of infection, is presently unknown. MethodsImmunocompromised individuals (n=404) and healthy controls (n=82) participated in a prospective clinical trial encompassing two doses of the mRNA BNT162b2 vaccine. Immunocompromised individuals included primary immunodeficiencies (PID) and secondary immunodeficiencies caused by human immunodeficiency virus (HIV) infection, allogeneic hematopoietic stem cell transplantation (HSCT)/chimeric antigen receptor T cell therapy (CAR-T), solid organ transplantation (SOT), and chronic lymphocytic leukemia (CLL). Saliva and serum samples were collected at four time points from the first vaccine dose until 2 weeks after second dose. SARS-CoV-2 spike specific immunoglobulin G (IgG) responses were quantified by a multiplex bead-based assay in saliva and correlated to paired serum IgG titers determined by Elecsys(R) Anti-SARS-CoV-2 S assay. ResultsIgG responses to the SARS-CoV-2 spike full-length trimeric glycoprotein (Spike-f) and S1 subunit in saliva in the HIV and HSCT/CAR-T groups were comparable to healthy controls. In contrast, PID, SOT, and CLL patients all displayed weaker responses which were mainly influenced by disease parameters or immunosuppressants. Salivary IgG levels strongly correlated with serum IgG titers on days 21 and 35 (rho=0.8079 and 0.7768, p=<0.0001). Receiver operating characteristic curve analysis for the predictive power of salivary IgG yielded AUC=0.95, PPV=90.7% for the entire cohort on D35. ConclusionsSaliva conveys humoral responses induced by BNT162b2 vaccination. The predictive power makes it highly suitable for screening low responding/vulnerable groups for revaccination. Trial RegistrationClinicalTrials.gov Identifier: NCT04780659 FundingKnut and Alice Wallenberg Foundation, Erling Perssons family foundation, Region Stockholm, Swedish Research Council, Karolinska Institutet, The Swedish Blood Cancer Foundation and the organization for PID patient group in Sweden, and Nordstjernan AB. Center for Medical Innovation (CIMED), the Swedish Medical Research Council and the Stockholm County Council (ALF). GRAPHIC ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/21264377v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1428efcorg.highwire.dtl.DTLVardef@b97e88org.highwire.dtl.DTLVardef@224661org.highwire.dtl.DTLVardef@3ab25a_HPS_FORMAT_FIGEXP M_FIG C_FIG
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BackgroundDeclining 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. MethodsUsing 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). ResultsSalivary 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. ConclusionsUnlike 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.
