COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva

Randad, Pranay R.; Pisanic, Nora; Kruczynski, Kate; Manabe, Yukari C.; Thomas, David; Pekosz, Andrew; Klein, Sabra L.; Betenbaugh, Michael J.; Clarke, William A.; Laeyendecker, Oliver; Caturegli, Patrizio P.; Larman, H. Benjamin; Detrick, Barbara; Fairley, Jessica K.; Sherman, Amy C.; Rouphael, Nadine; Edupuganti, Srilatha; Granger, Douglas A.; Granger, Steve W.; Collins, Matthew; Heaney, Christopher D.

Non-invasive SARS-CoV-2 antibody testing is urgently needed to estimate the incidence and prevalence of SARS-CoV-2 infection at the general population level. Precise knowledge of population immunity could allow government bodies to make informed decisions about how and when to relax stay-at-home directives and to reopen the economy. We hypothesized that salivary antibodies to SARS-CoV-2 could serve as a non-invasive alternative to serological testing for widespread monitoring of SARS-CoV-2 infection throughout the population. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology and tested 167 saliva and 324 serum samples, including 134 and 118 negative saliva and serum samples, respectively, collected before the COVID-19 pandemic, and 33 saliva and 206 serum samples from participants with RT-PCR-confirmed SARS-CoV-2 infection. We evaluated the correlation of results obtained in saliva vs. serum and determined the sensitivity and specificity for each diagnostic media, stratified by antibody isotype, for detection of SARS-CoV-2 infection based on COVID-19 case designation for all specimens. Matched serum and saliva SARS-CoV-2 antigen-specific IgG responses were significantly correlated. Within the 10-plex SARS-CoV-2 panel, the salivary anti-nucleocapsid (N) protein IgG response resulted in the highest sensitivity for detecting prior SARS-CoV-2 infection (100% sensitivity at ≥10 days post-SARS-CoV-2 symptom onset). The salivary anti-receptor binding domain (RBD) IgG response resulted in 100% specificity. Among individuals with SARS-CoV-2 infection confirmed with RT-PCR, the temporal kinetics of IgG, IgA, and IgM in saliva were consistent with those observed in serum. SARS-CoV-2 appears to trigger a humoral immune response resulting in the almost simultaneous rise of IgG, IgM and IgA levels both in serum and in saliva, mirroring responses consistent with the stimulation of existing, cross-reactive B cells. SARS-CoV-2 antibody testing in saliva can play a critically important role in large-scale “sero”-surveillance to address key public health priorities and guide policy and decision-making for COVID-19.