About COVID-19 Serological testing

The global pandemic of COVID-19 continues to affect the world since its emergence late last year.  Several weeks ago, Biofortis explained to you in a synthetic way the principle of RT-PCR detection analysis of the coronavirus, and many of us unfortunately met or heard about these nasopharyngeal swabs from relatives. There are, however, other category of tests that are increasingly being discussed: serological tests.

Immune response

As with most pathogens (viruses or bacteria),  it is possible to look for the trace that our immune system has kept, in other words to analyze the immune response of the patient.

Indeed, when an infectious agent enters our body for the first time, it will enter the infectious phase after several days of incubation, and will cause more or less symptoms. At this stage, detecting the pathogen directly is the most effective. This is the reason why the 1st intention test for COVID-19 is to look for the presence of SARS-CoV-2 by the RT-PCR method. 

In a second phase, the human body will begin to defend itself through its immune system. This response will be based on the production of molecules that will detect and neutralize the infectious agent: the antibodies. Note that during this second phase the virus particle could be undetected anymore.

Regarding COVID-19, 3 classes of antibodies are involved in the defense mechanism: Immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM). All 3 can be detected in the patients’ blood, and more especially in the serum. Within all classes can be found antibodies which are specific to an element (an antigen) of the SARS-CoV-2 virus particle (ex. some antibodies target proteins of the nucleocapsid).

These 3 classes have significantly different roles, and as such have different production cycles compared to the initial infection. Thus, a few days after the start of the infection by SARS-CoV-2, increase in the first place IgA and IgM, then only IgG. Regarding the blood concentrations of these 3 antibodies, there is a certain inter-individual variability. It has thus been shown that the IgA increase is linked to the severity of the disease. Several weeks after infection, the IgA and IgM concentrations will decrease and it is the IgG that will be the most present since IgG is related to long term immunity.

Chronological evolution of Covid-19 and most likely associated in vitro diagnostric results in symptomatic patients

Serological testing

 In term of serological testing, blood tests will consist of looking for SARS-CoV-2 specific antibodies of one or the other of the 3 classes of antibodies, or even 2 classes at a time. In all cases, the principle will be to catch the antibodies by presenting a SARS-CoV-2-like antigens which has been artificially produced. The link between antibodies and antigens will then be detected by a colorimetric reaction as in lateral flow test or ELISA (enzyme-linked immuno-sorbent assay), or also by a luminescence as in ECLIA (electrochemiluminescence immunoassay).

Main analytical steps of the IVD test to detect SARS-CoV-2 antibodies

In practice, the performance of these tests will depend on the type of antibody targeted (IgA, or IgM, or IgG or a combination), on the specificity of the targeted antibodies (and therefore on the SARS-CoV-2 type antigens used), but mainly on when the analysis is performed. An IgM test done too late or an IgG test done too early could be negative. It’s the reason why the choice of the method shall be related to patient’s history. In case of a positive serological test, it should be noted that it is currently difficult to know 1 / if the patient is still contagious or not, 2 / if he has definitively acquired his immunity. Consequently, we must still maintain our vigilance for the good of all.

What is not really known today is if the immune system will keep the memory of these antigens, so if a person who has been exposed to the virus will be protected in the long term.

– Thomas Carton, Scientific Operations Manager, Biofortis Mérieux Nutrisciences –

Biofortis clinical center of Mérieux NutriSciences can provide virological and serological diagnostic test. Biofortis only uses methods recognized by public health authorities.

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–    To know more –

Ma, H., Zeng, W., He, H. et al. Serum IgA, IgM, and IgG responses in COVID-19. Cell Mol Immunol 17, 773–775 (2020). https://doi.org/10.1038/s41423-020-0474-z

Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. 2020;323(22):2249–2251. doi:10.1001/jama.2020.8259

https://jamanetwork.com/journals/jama/fullarticle/2765837