SUMMARY: This study characterized antibody responses induced by COVID-19 mRNA vaccination and SARS-CoV-2 infection in saliva. Utilizing multiplex microsphere-based immunoassays, we measured saliva anti-SARS-CoV-2 spike IgG, IgA, and secretory IgA in 1,224 saliva samples collected from healthcare workers in the Prospective Assessment of SARS-CoV-2 Seroconversion study between August of 2020 through December of 2022. By spring of 2022, most individuals had detectable spike-specific antibodies in saliva. Longitudinal measurements of saliva anti-SARS-CoV-2 nucleocapsid IgG revealed that most spike-specific IgA and secretory IgA detected in saliva was driven by subclinical and clinically-evident infections, rather than by vaccination alone. In contrast, saliva anti-SARS-CoV-2 spike IgG was strongly induced by vaccination and exhibited improved durability with hybrid immunity. Baseline levels of saliva antibodies to the endemic human coronaviruses positively correlated with post-vaccination anti-SARS-CoV-2 spike IgG levels. This study provides insights for development of vaccines that generate mucosal antibodies to respiratory pathogens. HIGHLIGHTS: Saliva anti-spike antibodies were present in > 90% of participants by spring 2022 Saliva anti-spike IgA was driven by subclinical and clinically evident infections COVID-19 mRNA vaccination alone was a weak inducer of saliva IgA antibodies HCoV immunity correlates with post-vaccine anti-spike saliva antibody levels

PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100^® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.