key: cord-0874390-aqgono1k
authors: Lippi, Giuseppe; Mattiuzzi, Camilla
title: Clinical value anti‐SARS‐COV‐2 serum IgA titration in patients with COVID‐19
date: 2020-09-30
journal: J Med Virol
DOI: 10.1002/jmv.26539
sha: 5f1730827c362e98a471dd4688af9db54cfd9840
doc_id: 874390
cord_uid: aqgono1k

Immunoglobulins A (IgA) represent the major antibody class that offers humoral protection against microbial pathogens at surface of respiratory, genitourinary and gastrointestinal mucosae. This article is protected by copyright. All rights reserved.

To the Editor, Immunoglobulins A (IgA) represents the major antibody class that offers humoral protection against microbial pathogens at surface of respiratory, genitourinary, and gastrointestinal mucosae. 1 Although a comprehensive description of IgA biology shall be omitted here for space constrains, it seems important to mention that two major monomeric subclasses of this immunoglobulin can be synthesized, known as IgA1 and IgA2, which mostly differ for the structure of the hinge region and tissue distribution (e.g., IgA1 is more abundant and can be found on all mucosal surfaces, whilst IgA2 is synthesized at the lower extent and is prevalently found in the colon). 2 Beside specific molecular characterization, IgA can also be arranged throughout a vast array of combinations, the most frequent of which encompass monomeric and dimeric forms. The former structure characterizes internal body fluids (e.g., blood and cerebrospinal fluid), whilst the dimeric form (also known as "secretory IgA" [sIgA]), encompassing the association of two single monomeric IgA linked through a joining (J) chain, is more typically found in external fluids and secretions, where these antibodies play a critical role in mucosal immunity and protection against pathogens which colonize and/or invade mucosal surfaces. 2 Owing to the essential role in protecting the organism against respiratory pathogens, several lines of evidence hint that IgA-mediated defense may be also an essential part of immune protection against severe acute respiratory syndrome coronavirus disease (SARS-CoV-2), the virus causing the ongoing coronavirus disease 2019 pandemic. 3 In a recent article published in this journal, Xue et al. 4 Beside the putative role in disease prognostication and mucosal immunity, serum IgA titration may also offer important support for diagnosing acute SARS-CoV-2 infections. In a recent study, Infantino et al. 9 showed that anti-SARS-CoV-2 IgA titer was over twofold higher than that of anti-SARS-CoV-2 IgG 9 days after symptoms onset, but also that the early seropositivity rate of anti-SARS-CoV-2

IgA was double that of anti-SARS-CoV-2 IgG in anti-SARS-CoV-2

IgM-negative patients. In another interesting study, Sterlin et al. 10 showed that the overall seropositivity rate of anti-SARS-CoV-2 IgA targeting receptor binding domain and viral nucleocapsid protein was comparable to that of anti-SARS-CoV-2 IgG, and consistently higher than that of anti-SARS-CoV-2 IgM. This evidence pinpoints that early humoral neutralizing immunity against SARS-CoV-2 may be predominated by anti-SARS-CoV-2 IgA.

Reliable evidence that the anti-SARS-CoV-2 IgA serum titer would accurately reflect that of anti-SARS-CoV-2 sIgA has been provided in the study of Randad et al., 11 who showed very high correlations (i.e., up to 0.85) between the concentration of serum and saliva SARS-CoV-2 antigen-specific IgA. This would essentially suggest that assessment of serum anti-SARS-CoV-2 IgA may yield reliable information on the status of anti-SARS-CoV-2 mucosal immunity.

In conclusion, recent data are seemingly converging to confirm the many important clinical aspects mirrored by measuring anti-SARS-CoV-2 serum IgA in patients with COVID-19, so that their titration would be effective for improving the accuracy of diagnosing SARS-CoV-2 infection in patients with negative or undetermined results of molecular testing, for enhancing the

Regulation of IgA synthesis at mucosal surfaces

The function of immunoglobulin A in immunity

The role of IgA in COVID-19

Predictive effects of IgA and IgG combination to assess pulmonary exudation progression in COVID-19 patients

Characteristics and roles of severe acute respiratory syndrome coronavirus 2-specific antibodies in patients with different severities of coronavirus 19

A cross-reactive human IgA monoclonal antibody blocks SARS-CoV-2 spike-ACE2 interaction

Expansion of SARS-CoV-2-specific antibody-secreting cells and generation of neutralizing antibodies in hospitalized COVID-19 patients

Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays

Closing the serological gap in the diagnostic testing for COVID-19: the value of anti-SARS-CoV-2 IgA antibodies

IgA dominates the early neutralizing antibody response to SARS-CoV-2. medRxiv

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

T A B L E 1 Evidence supporting the clinical importance of routine assessment of anti-severe acute respiratory coronavirus disease 2 (SARS-CoV-2) serum immunoglobulin A (IgA) titer in patients with suspected or confirmed coronavirus disease 2019 (COVID-19) 1 

with negative or undetermined molecular biology 2. Enhance accuracy of anti-SARS-CoV-2 serological assessment 3. Mirror development of mucosal humoral immunity 4. Predict disease progression and severity