Nonlinear interdependence of the results of measuring anti-SARS-CoV-2 IgG levels using Abbott and Euroimmun test systems

One of the most important strategic challenges during the viral pandemic is the development of reliable and easy-to-use diagnostic tools that can test a large number of clinical samples of patient biological material in a short period of time. The generally accepted standard for SARS-CoV-2 virus detecting is based on rRT-PCR technology [1,2]. The RT-PCR test can be used effectively at an early stage of the disease but its diagnostic capabilities gradually decrease as the infection progresses especially after the disease symptoms disappear [3,4]. In contrast the immune response to SARS-CoV-2 (both humoral and cellular) is a long-term marker of past infection [5], [6], [7], [8]. Seroconversion almost always occurs after confirmed COVID-19 even if the disease is mild [9], [10], [11]. The rate of formation and persistence of antibodies against SARS-CoV-2 depends on many factors: the severity of the disease and the time of blood sampling after the onset of COVID-19 symptoms [12,13], age [14], cross-reactions due to previous diseases with coronaviruses of previous generations and vaccination with non-specific vaccines [15] and genetics component [16,17]. The antibodies blood level is affected by the functional of innant immunity as well as the balance between the links of adaptive immunity - cellular and humoral. The antibodies blood level depends on the intensity of cellular immunity [18], the presence of OAS1 gene "Neanderthal" variants [19] and also different genetic variations of ACE2 receptors, TMPRSS2 gene, interferon receptor (IFNAR) complex, interferon-induced transmembrane proteins (IFITM), 2′-5′-Oligoadenylate synthase (OAS) family genes, Interleukin 6 и 1 (IL-6 и IL-1), toll-like receptors TLRs, Human Leukocyte Antigen (HLA) and some others [16]. Due to differences in individual manifestations of COVID-19 the intensity of humoral immunity in people infected with SARS-CoV-2 can vary by more than 1000 times [20], [21], [22]. At the same time, there is a significant variation in the number of circulating antibodies to different proteins of the virus between patients [23,24].

The knowledge of the quantitative and qualitative aspects of the antibody response to SARS-CoV-2 infection over time is extremely important for understanding the stages of development and extinction of antiviral immunity being the basis for epidemiological surveillance and a guideline for determining public health measures aimed at limiting the pandemic spread.

Today in routine medical practice there are significant number of test systems used to determine the level of antibodies to SARS-CoV-2 which differ both in the methods underlying testing (enzymatic immunoassay, chemiluminescent analysis, chromatography method) and in the antigenic targets used and classes of measured immunoglobulins [25], [26], [27], [28]. The diagnostic performance of tests even based on the same methodological platform varies quite widely [29]. Moreover most of the test systems used in clinical practice differs in level indication terms of anti-SARS-CoV-2 immunoglobulin (measurement units). Consequently the results of measuring the antibodies to SARS-CoV-2 virus antigens levels using certified commercial tests are practically inconsistent with each other.

Meanwhile the ability to compare the results of measurements by available testing systems in quantitative terms will significantly expand our ability to track the stages of herd immunity development not only in a separate population but also on a global scale as well as in assessing the effectiveness of anti-COVID vaccines and booster vaccinations planning.

Obviously it is better for long-term monitoring to be carrying out on test systems of the same manufacturer. However this is not always possible when a patient is seeking for testing to different laboratories or when it is necessary to summarize a large pool of data from various sources.

To solve this problem and to facilitate the comparison among different serological tests, the World Health Organization (WHO) has established and distributed reference material based on a standard serum pool collected from human donors having suffered from COVID-19 [30]. In this standard preparation, the quantity of antibodies is defined as 1000 neutralization antibody units (IU) corresponding to 1000 Binding Antibody Units (BAU) per mL.

Observations for several months of specific immunoglobulins level dynamics in a fairly large group of people who had COVID-19 [31,32] drew our attention to the following phenomenon: the results of measurements of anti-SARS-CoV-2 immunoglobulins level using various serological tests converted to BAU/mL using standardized coefficients recalculation often differ significantly for the same clinical sample. Having systematized the preliminary data we became convinced of the need for a more detailed study of this problem and an explanation of the nature of the recorded discrepancies in the measurement results.

The aim of present study is a comparison of tests results of anty-SARS-CoV-2 IgG levels for two test systems widely used in clinical and laboratory practice manufactured by EuroImmun (Germany) and Abbott Architect (Ireland). In the test systems we have chosen for comparison the antigenic target to which the antibodies are directed is receptor binding domain of the S1 subunit of the spike protein of SARS-CoV-2 (RBD) for Abbott Architect [33] and all S1 glicoprotein subunit for EuroImmun [34] as it is generally accepted that responses against S1 or RBD are the best indicators of prior SARS-CoV-2 infection or vaccination effects [22,[35], [36], [37], [38]]. At the same time the compared tests are based on different methodological platforms (Abbott Architect uses the immunochemiluminescence method, CMIA (chemiluminescent microparticle immunoassay), and Euroimmun uses the enzyme immunoassay method, ELISA (enzyme-linked immunosorbent assay). Accordingly the tests compared in present study differ in units of anti-SARS-CoV-2 immunoglobulin levels measurement.

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