The importance of IgA detection in COVID-19 diagnostic testing

Serological diagnosis of SARS-CoV-2 infections strongly focus on IgG and IgM detection. It is assumed that IgM is the first antibody produced in response to the infection whereas IgG, which is synthesized later but shows enduring presence, has an impact on long-term immunity. In contrast, IgA is the major antibody class found in mucosal membranes including saliva, gastrointestinal tract and especially the respiratory epithelium which plays an important role in SARS-CoV-2 infections. Its function is to protect from infections of mucosal membranes and thereafter entry into the body of viruses and other pathogens and can be regarded as first line of defense especially for respiratory pathogens. In addition to its function as secreted antibody, IgA can be detected in serum as well.

Despite a research focus on IgG and IgM detection, SARS-CoV-2 specific IgA response in serum was reported in several studies [1][2][3]. IgA was reported to appear as early as IgM with a median duration of 5 days after symptom onset for seroconversion. Interestingly, the IgA response in the early stage of the disease seems to be more pronounced than IgM [2]. One study that examined 41 samples from COVID-19 patients collected within 7 days after symptom onset could detect specific IgA antibodies in 38 samples (93%) whereas only 35 samples (85%) showed detectable IgM antibodies [1]. Another study testing 535 samples from hospitalized COVID-19 patients showed a seroconversion in a total antibody assay (including IgA) for 93% of patients whereas IgG and IgM testing for the same samples showed a positive result in only 65% and 83% of the cases, respectively [4]. These results underline the potential importance to include IgA detection for the serological assessment of COVID-19 patients. This is further supported by a study testing 17 samples from the first 10 days after disease onset with an ELISA using RBD as antigen. 15 of 17 samples (88%) reacted positive for IgA compared to only 13 (75%) and 11 (65%) for IgM and IgG respectively [5]. The authors concluded that “Although IgM reached its peak at early stages, its detecting sensitivity is lower than that of IgA and IgG. Our data suggest that IgM has the lowest diagnostic power among the three types of antibodies for diagnosing SARS-CoV-2. Adding IgA into a diagnostic kit that contains IgG and IgM improves the serologic testing power at both early and late stages.”

In addition to an increased sensitivity, monitoring of the IgA response could provide additional diagnostic value. A recent case study performed with COVID-19 patients in the University Medical Center Hamburg-Eppendorf, Germany identified a connection between disease severity and the SARSCoV- 2 specific IgA response [6]. Soon after disease onset in a mild case a SARS-CoV-2-specific IgA response was observed that decreased during the course of the disease. In contrast, a case with more severe progression showed a delayed, but eventually very strong and broad SARS-CoV-2-specific IgA response. In this study, the IgM response showed no clear trend. The authors concluded that “IgA is considered a major effector molecule involved in defense mechanisms against viruses and infections with respiratory viruses that can induce efficient IgA responses in secretions as well as in sera. Our data suggest that IgA antibodies are valuable diagnostic markers that show strong signals early after onset of mild COVID-19-associated symptoms and that IgA antibodies may be crucial for efficient clearance of SARS-CoV-2. […] Furthermore, we show that the IgA response may be highly relevant in disease progression and should be further investigated.”

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