key: cord-0964986-7ltzu2ub
authors: Cheng, Zhangkai J.; Zheng, Peiyan; Xue, Mingshan; Chen, Youpeng; Sun, Baoqing
title: Identifying COVID-19 Infections From a Vaccinated Population Using Specific IgA Antibody Test
date: 2022-01-31
journal: Front Immunol
DOI: 10.3389/fimmu.2022.821218
sha: 59bfed52cbf6a10dc272168ff9969fee59037c5e
doc_id: 964986
cord_uid: 7ltzu2ub

We analyzed the serum from COVID-19 patients and vaccinated subjects, and found that the specific IgA titer level could be used to assist COVID-19 diagnosis, especially in China.

When specific antibodies IgA, IgM and IgG levels were compared between virus infection and vaccination, IgA was found to have the most significant difference (see Supplementary S2 for IgM and IgG results). Figure 1A shows IgA levels at each time point. Figure 1B shows the distribution of SARS-CoV-2-specific IgA antibodies. The geometric mean titer (GMT) of IgA level in Pfizer-BioNTech vaccine cohort was 0.81, with a positive (titer≥1) rate of 45%; Sinopharm vaccine cohort was 0.17, with a positive rate of 2.2%; CoronaVac cohort was 0.23, with a positive rate of 4.2%; mild patients cohort were 1.7, with a positive rate of 48.1%; severe patients cohort were as high as 17.4, with 100% positive rate. IgA levels in the patient cohort were significantly higher than IgA levels in the vaccine cohort (P<0.05, all vaccinated vs. all infected). The level of IgA in mild patients started low at the beginning of infection detection, and rose after a few days into the infection.

Infected patients were found to have much greater IgA levels than vaccinated people after being infected for the same number of days as the vaccination. The SARS-CoV-2-specific antibodies in humans are likely to be produced in response to vaccination or infection, but an important difference between the two is that during virus infections, the main infection sites receive long-term high levels of stimulation, which induces strong mucosal immune responses and is reflected in the rise in IgA levels. This is consistent with multiple previous studies, which have found that the positive rate of specific IgA in a COVID-19 infection can reach over 50% within a week of confirmed infection (2, 3) , with specific IgA titer levels peaking in the third week and the positive rate reaching 100% (2, 4) . The IgA antibody levels were found to continue to remain high (within 42 days of onset) (2, 3, 5) . Furthermore, according to our analysis, the specific IgA levels of the vaccine cohort were lower than the minimum IgA level of the severe patient cohort in more than 68% of mRNA vaccine cohort, and more than 95% of inactivated vaccine cohort. In addition, we used the data to create a receiver operating characteristic (ROC) curve of IgA antibody to determine SARS-CoV-2, regenerating an area-under-the-curve (AUC) of 0.862 ( Figure 1C) , which further verified our hypothesis. The accuracy is further increased when excluding subjects who have received mRNA vaccines, resulting in an AUC of 0.895. Our results show that using specific-IgA titer levels to diagnose COVID-19 infection has a high prediction value, especially in a population where most of the population is vaccinated with inactivated vaccines, such as China. For most other vaccines, anti-nucleocapsid antibodies can be used as a tool to distinguish infected from vaccinated individuals, and should have a higher specificity compared to IgA titers (6) . However, this is not the case for inactivated vaccines, as these should also induce antibodies against the nucleocapsid protein. As a result, we conclude that using the SARS-CoV-2-IgA antibody as a differential diagnosis of infection has a certain clinical reference significance.

The data that support the findings of this study are available upon reasonable request from the corresponding author.

The studies involving human participants were reviewed and approved by First Affiliated Hospital of Guangzhou Medical University Ethical Committee. The patients/participants provided their written informed consent to participate in this study.

All authors made substantial contributions to the writing of this review, revised it critically for important intellectual content, approved the version to be published, and agreed to be accountable for all aspects of this review. All authors agreed with the content of this review and gave explicit consent to submit. 

Public Health Measures and the Control of COVID-19 in China

Serum IgA, IgM, and IgG Responses in COVID-19

IgA-Ab Response to Spike Glycoprotein of SARS-CoV-2 in Patients With COVID-19: A Longitudinal Study

Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)

Evaluation of Commercial and Automated SARS-CoV-2 IgG and IgA ELISAs Using Coronavirus Disease (COVID-19) Patient Samples

Comparing Immunoassays for SARS-CoV-2 Antibody Detection in Patients With and Without Laboratory-Confirmed SARS-CoV-2 Infection

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2022.

Conflict of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.