A study by Long et al., recently published in the renowned scientific journal "Nature" (https://doi.org/10.1038/s41591-020-0965-6), strongly emphasizes why it is necessary, during and after the corona pandemic, to use readily available and efficiently performed antibody tests such as enzyme-linked immunosorbent assays (ELISA).
In the study mentioned above, Chinese researchers around Long and Huang compared samples from the megacity Chongqing. They examined samples of 74 patients with and without symptoms. After an infection, the body generates an immune response to eliminate a pathogen. The immune system first produces IgM and IgA antibodies. Once the pathogen is recognized and fought, IgG antibodies are produced. IgG antibodies offer some protection against future SARS-CoV-2 infections and are detected in the blood as so-called antibody titers. These IgG antibodies form the memory of the immune system for many years. Vaccines work similarly by teaching the immune system to produce antibodies to protect against specific pathogens.
Quantitative antibody tests that target neutralizing antibodies are among the most important tools for clinicians to determine a titer that reflects the value of a protective immune response to infection. Thus, the titer required for an effective vaccine can easily be determined using our SRS-CoV-2 AESKULISAs.
Long et al. have investigated this fact by measuring IgM and IgG levels in patient samples using ELISA. Even though the sample of patients is small, the study shows no insignificant decrease in antibodies in the patient group with mild to mild symptoms. Only 62.2 percent of patients in the group without symptoms still had antibodies in their blood a few weeks after infection. In the group of symptomatic patients, 78.4 percent still had antibodies in their blood.
After approximately eight weeks, follow-up examinations showed that the antibody concentration in the blood of the symptom-free patients decreased by 81.1 percent. In the group of symptomatic patients, the decrease was only 62.2 percent. The group of Long and Huang also identified patients positive for SARS-CoV-2 by ELISA, who had previously been categorized as negative by RT-PCR. An examination of the samples for cytokines involved in the immune reaction, including G- and M-CSF, IL2, IL6, CCL2, IFN-γ, shows that patients with symptoms had a higher value of these proteins, which indicates a stronger immune response.
Even though the study mentioned above only involved a comparatively small sample, the results cast doubt on previous assumptions that strong symptoms represent a high risk of infection and that anyone who has survived an infection is immune to future infections.
At Imperial College London, Professor Altmann confirms the present study, stating that most infected people show only mild or no symptoms at all. The crucial question is whether they have sustained protective immunity. For him, it is an essential but also worrying point, that many patients in the study showed a significant drop in antibody concentration only 6-7 weeks after the disease's onset. Long et al. write that the decrease in IgG and neutralizing antibodies in early convalescence will influence the immune strategy and serological investigations.
That is precisely where AESKU sees the primary clinical utility of its quantitaive AEKULISA SARS-CoV-2 tests and offers six different kits for detection and monitoring of the immune status.
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A secure future thanks to quantitative SARS-CoV-2 AESKULISA tests
In the current situation, it is hardly necessary to argue about the urgent need for an effective and robust vaccine to treat COVID-19, because our society and humanity itself are in a state of emergency. However, not only a vaccine is urgently needed, but the success of vaccination must also be verified using quantitative tests. Quantitative tests react to neutralizing antibodies, i.e., antibodies responding to a pathogen and breaking it down, make it possible to determine the success of an immune response and a vaccination in everyday practice.
For the determination of an immune reaction, the examination of immunoglobulins, so-called antibodies, has been established for years. Since protein structures on the surface of a pathogen (bacterium, virus) are specific, i.e., unique for individual structures, the immune system forms the appropriate antibody; it is possible to examine different antibodies for confirmation and infection. In the case of SARS-CoV-2 viruses, the nucleocapsid protein (N) and the spike protein (S1) are suitable.
AESKU offers six different immunoassays:
AESKULISA® SARS-CoV-2 NP IgA* / IgG* / IgM*
AESKULISA® SARS-CoV-2 NP IgA, IgG, and IgM tests are qualitative and quantitative immunoassays for the detection of human IgM, IgA, and IgG antibodies in serum or plasma directed against SARS-CoV-2 in highly conserved nucleocapsid protein (NP). The nucleocapsid protein is very reactive and stimulates a strong immune response. This potent immune response provides a very sensitive detection of antibodies, which allows a clear differentiation between positive and negative samples.
They are, therefore, ideal for IgA, IgG, and IgM detection for screening and diagnosis. Due to the high sensitivity and the strong conservation of the nucleocapsid protein in the coronavirus family, the risk of cross-reaction with antibodies against SARS-CoV-1 is increased. Since antibodies against the nucleocapsid protein have no neutralizing effect, they are not suitable for determining the immune status, the so-called antibody titer.
AESKU uses immunogenic nucleocapsid proteins of SARS-CoV-2 expressed in insect cells for the sensitive detection of IgM, IgA, and IgG antibodies.
Table 1: Sensitivity and specificity of AESKULISA® SARS-CoV-2 NP IgA, IgG
and IgM immunoassays were assessed by the analysis of 76 serum samples from healthy blood donors (2018) and 20 individuals with clinically confirmed COVID19 using the clinical findings as a reference.
AESKULISA® SARS-CoV-2 S1 IgA/ IgG / IgM
AESKULISA® SARS-CoV-2 S1 IgA, IgG, and IgM tests are qualitative and quantitative immunoassays for the detection of human IgM, IgA, and IgG antibodies in serum or plasma directed against SARS-CoV-2 by the highly specific spike protein (S1). The spike protein has the advantage over the nucleocapsid protein that is highly specific for the SARS-CoV-2 virus.
Resulting in a much lower risk of cross-reactions with antibodies against other members of the coronavirus family. IgG antibodies react against the receptor-binding domain (RBD) on the spike proteins. They are considered to be neutralizing and, therefore, suitable for monitoring the antibody titer of patients.
Table 2: Sensitivity and specificity of AESKULISA® SARS-CoV-2 S1 IgA/IgG/IgM
* Submitted for EUA
Test Kit Components
- Aluminium-sealed and coated MTP with breakable cavities
- 4 Calibrators (A – D), Calibrator B = cut off Calibrator
- Positive and Negative Control
- Sample Dilution Buffer (5x conc.; for IgM detection incl. Rf Absorbent)
- Wash Buffer (50x conc.)
- Conjugate (anti-human IgG / IgA / IgM conjugated to POD)
- Substrate (TMB) and „Stop Solution“
- Quality Control Certificate and Instruction Manual
Severe acute respiratory syndrome (SARS)-CoV, as well as Middle Eastern respiratory syndrome (MERS) and SARS CoV 2 (SARS-CoV-2), belong to the family of Coronaviridae. All these three viruses are pathogenic and cause respiratory problems in humans. In December 2019, several unexpected cases of pneumonia were observed in China.
The government and health researchers in that country pursued strategies to control the virus's outbreak and programmed an etiological study. Finlay, the World Health Organization (WHO) announced that SARS-CoV-2 would cause coronavirus disease in 2019 (COVID-19).
The incubation period of COVID-19 is estimated to be 1 to 14 days. The lung is the main organ affected by COVID-19. However, in severe cases, other parts of the body, such as the central nervous system (CNS), kidney, liver, heart, stomach, and intestines may also be affected. As with many other respiratory diseases, the severity of the infection caused by SARS-CoV-2 can vary from patient to patient.
Recent evidence suggests that some SARS-CoV-2 infection cases have been associated with pneumonia and respiratory distress, while other patients diagnosed with SARS-CoV-2 have experienced respiratory failure, septic shock, or multi-organ failure. The mortality rate of infection is reported to be about 2%. The infection of other people during the incubation period and an acute symptom-free phase of the disease is possible.