Clinical Assessment of SARS-CoV-2 Antibodies in Oral Fluids Following Infection and Vaccination

Abstract

Background: SARS-CoV-2 variants continue to circulate globally, even within highly vaccinated populations. The first-generation SARS-CoV-2 vaccines elicit neutralizing immunoglobin G (IgG) antibodies that prevent severe COVID-19 but induce only weak antibody responses in mucosal tissues. There is increasing recognition that secretory immunoglobin A (SIgA) antibodies in the upper respiratory tract and oral cavity are critical in interrupting virus shedding, transmission, and progression of disease. To fully understand the immune-related factors that influence SARS-CoV-2 dynamics at the population level, it will be necessary to monitor virus-specific IgG and SIgA in systemic and mucosal compartments.

Content: Oral fluids and saliva, with appropriate standardized collection methods, constitute a readily accessible biospecimen type from which both systemic and mucosal antibodies can be measured. Serum-derived IgG and immunoglobin A (IgA) are found in gingival crevicular fluids and saliva as the result of transudation, while SIgA, which is produced in response to mucosal infection and vaccination, is actively transported across salivary gland epithelia and present in saliva and passive drool. In this mini-review, we summarize the need for the implementation of standards, highly qualified reagents, and best practices to ensure that clinical science is both rigorous and comparable across laboratories and institutions. We discuss the need for a better understanding of sample stability, collection methods, and other factors that affect measurement outcomes and interlaboratory variability.

Summary: The establishment of best practices and clinical laboratory standards for the assessment of SARS-CoV-2 serum and mucosal antibodies in oral fluids is integral to understanding immune-related factors that influence COVID-19 transmission and persistence within populations.

Fig. 1.

Immunoglobulin types and forms found in OF. Serum derived (A) IgG and (B) monomeric IgA are found in saliva and OF because of transudation. Mucosa-derived (C) dimeric IgA consists of 2 IgA monomers joined together by J chain. Dimeric IgA is actively transported across certain epithelia in the oral cavity by the polymeric immunoglobulin receptor and delivered into OF as (D) SIgA. Secretory component is a proteolytic cleavage product of polymeric immunoglobulin receptor and remains bound to dimeric IgA. For immunoassays, dimeric IgA and SIgA can be differentiated from serum-derived IgA using anti-J chain or anti-SC specific antibodies. Created with BioRender.com.