Understand how the new Coronavirus originated, how to diagnose, and what are the tests available and recommended, both for individuals who want to know whether they are infected or had contact with the SARS-COV2, the virus that causes COVID-19, and produced the necessary immunity antibodies.
Did you know that the body is capable of producing antibodies that prevent infectious agents, such as viruses, from infecting human cells? These antibodies are called neutralizing antibodies and are generally able to block the virus-cell binding sites, thus, blocking the viral entry points.
What are neutralizing antibodies?
Neutralizing antibodies are specific monoclonal glycoproteins, and the production of which is induced by the immune response of the virus during the infection, or through vaccination. These antibodies play an important role in the elimination (whitening) of viruses, with great potential for the prevention and/or treatment of viral diseases, since they have the ability to block infection.
The presence of monoclonal antibodies targeting vulnerable sites on viral surface proteins is increasingly recognized as a promising class of drugs against infectious diseases and has shown therapeutic efficacy for different viruses.
The presence of neutralizing antibodies is indicative of the body’s ability to produce antibodies in response to the invasion of infectious agents.
How did the COVID-19 originate?
In December 2019, in Wuhan, province of Hubei, China, some cases of severe pneumonia with unknown cause were reported and epidemiologically related to a seafood market in Wujan.
Then, in January 2020, a new coronavirus was identified, isolated in the lower respiratory tract of four suspected cases of severe pneumonia. This new coronavirus belonged to the family of viruses that cause severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), as well as the four human coronaviruses associated to common cold.
The new coronavirus SARS-COV-2, named initially 2019-nCOV by the World Health Organization (WHO) and later as SARS-COV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), is a virus that belongs to the family coronaviridae from the genus betacoronavirus. This virus causes the disease that became known as Corona Virus Disease (COVID-19).
On January 30, 2020, the World Health Organization declared that the outbreak of SARS-CoV-2 was a Public Health Emergency of international concern, and more than 80,000 confirmed cases were reported around the world by February 28, 2020.
Currently, more than 103 million people are infected worldwide, and more than two million lives have been lost to the disease.
Relationship between neutralizing antibodies and Coronavirus
It is already known that the entry of the virus into human cells occurs through the receptor of the angiotensin-converting enzyme 2 (ACE2) present on the surface of cells, in which the virus uses its viral spike protein, called Spike (protein S), to bind up and be its gateway to the body.
Protein S (Spike), has two functional subunits that allow cell binding. The receptor-binding region is located in subunit 1 (region of greatest interest), where the binding between protein S and the ACE2 cell receptor occurs. Subsequently, the fusion of membranes occur, and the virus enters the cell, where it begins its replication process.
The neutralizing antibodies of the coronavirus mainly target the S-glycoproteins on the surface of the virus that mediate their entry into host cells, thus preventing the potential binding of the virus to human cells, preventing the entry of the infectious agent and its replication in the body. Therefore, they are called neutralizing antibodies or viral-inhibiting antibodies.
Which test detects neutralizing antibodies?
The Neutralizing Antibodies test aims to qualify the immune response, analyzing the ability of antibodies to block the binding of protein S (Spike) to the receptor of human cells, the ACE2 protein. Therefore, revealing the quality of the defense response against Sars-Cov-2 only at the time of its conduction.
Because of this, it is possible to assess whether the individual has ever had contact with the new Coronavirus (Sars-Cov-2) and whether it has an immune response to it. Unlike the RT-PCR test or the antigen test that analyzes active viral infection.
How is the Synlab Total Antibody Neutralization test performed?
The Neutralizing Antibodies test is performed using a blood sample collected, where serum or plasma is extracted (5 mL of whole blood in a dry tube), and ideally the collection should be performed 21 days after the initial appearance of the clinical picture and symptoms, or positive PCR.
The SARS-COV-2 Total Antibodies Neutralization test is indicated for:
- Individuals who wish to identify the presence of antibodies produced against SARS-CoV-2 after contaminated by COVID19
- After vaccination;
- Individuals who were unable to undergo the diagnostic test, RT-PCR, at the time of the probable infection;
- Individuals who are not sure about whether they have been contaminated by COVID19
However, the test is contraindicated for the diagnosis of acute infection.
How is the result of the Synlab Total Antibody test for SARS-COV-2?
The test result is released as a percentage (%) of virus inhibition; of viral neutralization, and can be classified as follows:
- Non-reactive/negative results: less than 20%: without neutralizing activity, indicate absence of neutralizing antibodies for SARS-CoV-2.
- Reagent/positive results: greater than or equal to 30%, indicate the presence of neutralizing antibodies for SARS-CoV-2. However, the positive result does not allow to say how long the immunity will remain active.
- Undetermined results: results between 20% to 30%, are on the limit between positive and negative. They must be interpreted with caution, together with epidemiological, clinical data and preferably with other laboratory results, such as RT-PCR for SARS-CoV-2 and imaging tests. It is worthy of note that, in these cases, previous contact with the virus cannot be ruled out.
Negative results do not exclude contact with the virus; since there is variability between individuals in relation to the time of immune response for the production of antibodies to SARS-CoV-2 in COVID-19.
How to diagnose COVID-19?
The diagnostic medicine has a fundamental role in the global fight against the coronavirus. As a response to the COVID-19 pandemic, SYNLAB Solutions in Diagnostics, present in 40 countries and four continents, has different laboratory tools developed for different goals.
These laboratory tools, when adopted individually or as a set, allow developing protocols to obtain epidemiological data, occupational medicine, hospital discharge, return to the work environment or to life in society, among others.
The tests available for detecting COVID-19 can be divided into two classes:
1) Diagnoses for the new Coronavirus:
The diagnostic tests are used to verify whether the patient is infected. The test consists of detecting genetic material (RNA) from the SARS-COV-2 virus in nasopharyngeal samples and respiratory secretions. Is generally known as molecular testing or nucleic acid amplification techniques (NAAT). RT-PCR is the gold standard, but not the only molecular test.
RT-PCR Coronavirus test: can detect infection from the first day of symptom, in average, until the 21st day of infection
- Considered the gold standard for COVID-19 diagnosis.
- Molecular analysis, highly sensitive, enabling to identify contaminated patients soon after the symptoms appear up to approximately the 21st day since the infection. After this period, the amount of viral material (load) tends to decrease, making it more difficult to detect by this technique.
- Technique of choice in cases of monitoring infected patients, being mandatory for hospital discharge.
To whom the Coronavirus RT-PCR Test is indicated:
Since the RT-PCR test is a diagnostic test, which has the goal of assessing whether the patient is infected by the virus that causes COVID-19, is indicated for patients presenting symptoms or who have presented prior POSITIVE result, in order to find out whether they are still sick and infectious. Also indicated in contacts close to confirmed COVID-19 cases.
2) Assessment of immune response:
The tests for assessing the immune response are used to check whether the patient had prior contact and produced antibodies of immunity against the virus. The test consists of detecting antibodies that appear in the acute phase of infection (IgM/IgA) and/or antibodies that appear in the later phase of infection (IgG) and suggest immunity against the SARS-COV-2 virus in blood samples. It is important to consider that the time for these antibodies to appear may vary from person to person and in certain clinical conditions (such as immunosuppressed patients who may take a little longer to produce, or still haven’t produced, these antibodies).
Antibodies or Serology:
The serology tests consist on quantifying the antibodies produced against the SARS-COV-2 virus, that is, it assesses the response from the immune system to contact with the virus.
- Analysis of the immune response conducted in blood/serum samples;
- Production of antibodies in average after the 5th day of the disease
- Indicated for individuals after the 5th day from the onset of symptoms or exposure;
- Like every serology test, if the result is negative, the possibility of infection must not be excluded. Therefore, the result must be assessed by the requesting physician, who will check the need for repetition.
What are the types of test for serology?
Between 5 to 10 days after the contact or onset of symptoms:
- IgA/IgM: Antibodies of the IgA/IgM type indicate recent contact with the virus, or acute infection. Antibodies of the IgA/IgM appear in the beginning of infection and, after a while, start decreasing, until they are no longer detected.
Between 10 to 15 days after the contact or onset of symptoms:
- IgG: Antibodies of the IgG type indicate immunity, that is, the individual had contact with the virus and it was enough to create immunity antibodies (IgG). However, there still isn’t concrete information on whether IgG antibodies are permanent against SARS-COV-2, and whether it always generate immunity.
Quick test: The quick test also conducts the analysis of antibodies against SARS-COV-2. However, this analysis presents lower sensitivity and provides a qualitative result, that is, POSITIVE or NEGATIVE. It must be performed by a trained health professional and with all biosafety measures.
How is the COVID-19 quick test conducted?
- The test is conducted in a mobile device, through a capillary blood sample, in which the positive or negative result is visually interpreted by the appearance of bars for each antibody (IgM or IgG)
When must the COVID-19 quick test be conducted?
- When is it recommended?
Since it needs a higher amount of antibodies, it is recommended that it is conducted as of the 10th day after the contact or onset or symptoms.
- When is it not recommended?
Due to the long detection window period, its isolated use as a tool for acute/early detection is not recommended, because it may generate a high number of FALSE NEGATIVE results.
To whom is the COVID-19 quick test recommended?
The tests for analysis of antibodies are indicated for individuals who want to know whether they had contact with the virus and produced immunity antibodies, or for epidemiological control.
What are the differences between the PCR and Serology tests for COVID-19?
The difference between the COVID-19 tests consists on the purpose of the analysis, as well as the necessary sample, that is, to know whether the individual is or was infected.
For the RT-PCR test, considered the gold standard:
- It identifies whether the individual is infected.
- The virus is detected by the viral genetic material.
- – The higher the viral load, the better the sensitivity.
- the samples selected is the nasopharyngeal swab, however, other types of samples from the oropharynx or respiratory tract can be used.
For antibody or serology tests and quick test:
- It identifies whether the individual had contact with the virus.
- It identifies whether the individual produced immunity antibodies.
- The virus is detected by a serum or blood sample.
Despite the fact that the quick test and the serology test check the presence of antibodies against SARS-COV-2, they also are different from each other:
- The serology test allows to quantify the results, presenting higher sensitivity. Performed on automated equipment.
- The quick test is a qualitative test that needs a higher amount of antibodies to be able to make the detection, thus it has lower sensitivity. It does not require laboratory equipment for its interpretation.
What are the differences between the neutralizing antibody test to the other tests for COVID-19?
Both the RT-PCR test and the antigen tests aim to analyze the active viral infection, that is, determine whether the individual has COVID-19 at that time.
The Total Antibody tests (IgG and IgM) for COVID-19 are sensitive for detecting previous contact with the virus; however, they are not specific for detecting the neutralization of the virus.
The neutralizing antibody test, on the other hand, reflects viral neutralization, that is, if the virus protein S (Spike) has been blocked from binding to the ACE2 protein in human cells, and should not be used as a diagnostic test for the disease, as it does not determine the presence of the virus, as does RT-PCR.
As with other serological tests for COVID-19, the SARS-CoV-2 Neutralization test should not be interpreted as an indication of certainty of immunity (partial or total) to the virus, as the level and time of permanence of these antibodies are still being studied.
Is treatment with neutralizing antibodies possible?
An ongoing study investigates the use of an antibody cocktail called REGN-COV2, which contains two neutralizing antibodies against SARS-CoV-2, in outpatients with COVID-19. In which the authors main hypothesis is that the complications and deaths caused by COVID-19 are due to the high viral load of SARS-CoV-2, and that the reduction of this load can lead to clinical benefits. Preliminary results showed that the antibodies cocktail REGN-COV2 reduced viral load, with greater effect in patients whose immune response had not yet started or who had a high viral load at the beginning of the study.
REGN-COV2 is a cocktail made up of two non-competitive human neutralizing IgG1 antibodies, which target the SARS-CoV-2 protein S (spike) receptor binding region, thus preventing the virus from entering human cells through the angiotensin-converting enzyme 2 (ACE2) receptor.
According to authors, the cocktail approach is due to the fact that in a previous study using a single antibody, there was resistance to treatment due to new variants of the respiratory syncytial virus (RSV). Pre-clinical studies have confirmed that the REGN-COV2 cocktail protects against the rapid emergence of such variants seen in the use of any single antibody.
In vivo studies in primates have shown profound antiviral activity of REGN-COV2 in reducing viral load when administered in a prophylactic context and in improving viral clearance when administered in a therapeutic setting.
About the SYNLAB Group
The SYNLAB Group is a leader in providing medical diagnostic services in Europe, providing a full range of clinical laboratory analysis services to patients, healthcare professionals, clinics and the pharmaceutical industry. Resulting from the merger between Labco and Synlab, the new SYNLAB Group is the undisputed European leader in medical laboratory services.