Immunoglobulin A response to SARS-CoV-2 infection and immunity

Abstract

The novel coronavirus disease (COVID-19) and its infamous "Variants" of the etiological agent termed Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has proven to be a global health concern. The three antibodies, IgA, IgM, and IgG, perform their dedicated role as main workhorses of the host adaptive immune system in virus neutralization. Immunoglobulin-A (IgA), also known as "Mucosal Immunoglobulin", has been under keen interest throughout the viral infection cycle. Its importance lies because IgA is predominant mucosal antibody and SARS family viruses primarily infect the mucosal surfaces of human respiratory tract. Therefore, IgA can be considered a diagnostic and prognostic marker and an active infection biomarker for SARS CoV-2 infection. Along with molecular analyses, serological tests, including IgA detection tests, are gaining ground in application as an early detectable marker and as a minimally invasive detection strategy. In the current review, it was emphasized the role of IgA response in diagnosis, host defense strategies, treatment, and prevention of SARS-CoV-2 infection. The data analysis was performed through almost 100 published peer-reviewed research reports and comprehended the importance of IgA in antiviral immunity against SARS-CoV-2 and other related respiratory viruses. Taken together, it is concluded that secretory IgA- Abs can serve as a promising detection tool for respiratory viral diagnosis and treatment parallel to IgG-based therapeutics and diagnostics. Vaccine candidates that target and trigger mucosal immune response may also be employed in future dimensions of research against other respiratory viruses.

Keywords: COVID-19; Immune response; Immunoglobulin A (IgA); Mucosal immunity; SARS-CoV-2; Serological test; Vaccine.

Fig. 1

Monomeric and dimeric IgA. A) Left: The monomeric IgA (mIgA). The heavy chains are shown in orange and the light chains in purple. V: Variable region, C: Constant region. Right: The dimeric IgA (dIgA). dIgA contains the joining chain (J-CHAIN) linked by two disulfide bonds to the Fc region in the two different monomers. B) Schematic representation of the complex structure of SIgA with the secretory component. Chain names and corresponding C_H domains and Fcs are labeled with SC domains (1–5). Each SIgA component is depicted in a unique color. This figure is based on recently published papers [46]. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Schematic representation of serum antibody kinetics in SARS-CoV-2 infection. IgA, IgG, and IgM are represented. The figure describes an approximate timeline of appearance and subsequent decrease of each immunoglobulin isotype following a SARS-CoV-2 infection. The curves and values are based on recently published papers [6,78,79]. S.O. Symptom onset, W. week(s), PSO. Post-symptom onset.

Fig. 3

Schematic cartoon of the function of IgA in immunity (immune exclusion). A) Abrogating viral entry by blocking epithelial receptors for SARS-CoV-2. B) Entrapping viruses in mucus neutralizes SARS-CoV-2 before binding to epithelial cells. C) Targeting of myeloid dendritic cells.