Bangladesh needs to move forward with antibody test for Covid-19

In infectious disease diagnosis, two types of tests are carried out by and large. First one is an antigen test that allows us to identify the infectious agent (e.g. virus, bacteria). Antigen testing is widely used as it is imperative to identify a patient for treatment. An antigen testing is also essential to take a positive diagnosed person for quarantine or isolation to control further spread of the disease.

In antigen testing, presence of either pathogen's surface protein (e.g. NS1 protein for Dengue fever) or nucleic acid (RNA in case of Covid-19) can be detected to confirm an active infection.

An antibody test may help to get a better insight on who might have developed a degree of immunity to SARS-CoV-2. PHOTO: BLOOMBERG

However, if an antigen testing cannot be performed during an active infection, a second category of tests called "antibody tests" are applied to find out a recent infection. When an infected person recovers from the disease, pathogens disappear by the works of antibody generated from body's immune response. Therefore, detection of those antibodies can tell us about a recent infection. During a pandemic like Covid-19, both antigen and antibody tests are of paramount importance, because many active infection goes unidentified and inevitably antibody test remains as only option to spot an infection for a number of purposes.  

Antibody (immunoglobulin) is a large Y shaped protective protein produced by body's immune system. According to the constant region and activity, antibodies are classified into five groups, IgG, IgM, IgA, IgD, and IgE. The immune system of the body can recognise foreign substances or invading pathogen (antigen) as antigen's surface molecules are different from those found in the body. Antigen binds to body's specific antibody producing army of B-cell surface that stimulates its further proliferation and maturation. Antibodies are secreted into the bloodstream from the mature B-cells (plasma cells). The antibody binds to the antigen and inactivates the antigen in several ways, for instance, neutralisation (bind to toxin releasing site to prevent toxic effect), complement fixation (causes lysis, chemotaxis to attract microbe-killing scavenger cells that ingest the invader), and agglutination (cause clumping which makes it easier for phagocytes to capture the invader). Antibodies provide long term immunity against that particular antigen. In the case of Covid-19, IgG and IgM antibodies are produced during immune response. Initially, the immune system produces IgM, which provides the initial and quick humoral immunity during viral infections. IgG is usually produced 7 days after IgM appears. IgG provides long-term immunity and immunological memory.

The novel coronavirus SARS-CoV-2 attacks our organs that stimulates immune system to mount immune response (antibody production). On the other hand, if antibodies are found against the SARS-CoV-2 virus in a person's blood, it means that the person has overcome the infection of the virus. An antibody test cannot be used to determine whether a person is currently infected with the virus. Therefore, to diagnose the disease an antigen test is required (RT-PCR). Generally, an available antibody test is done to detect binding antibodies to know whether the body produced any antibody against SARS-CoV-2 and it does not indicate the effectiveness of the immune response. Those tests can only identify antibody subgroup, which may inactivate the virus. ELISA based methods can detect the type of antibodies as well the amount or titer of antibody. This type of tests can provide better insight into the effectiveness of the antibodies in protecting a person from another SARS-CoV-2 virus infection by blocking the virus.

The type of antibody test kits that came in discussion in recent days include rapid test kits (LFD, Dot Blot etc.) and ELISA based test kits. Antibody test kits can be used to acquire information on the spread of the virus. In simpler words, if we can find out how many people have already had Covid-19, it will let us understand the proportion of the population that are likely to get infected further. 

Antibody tests can also be used to find donors for plasma therapy. In plasma therapy, people with Covid-19 infection can be transfused with plasma containing antibodies against the SARS-CoV-2 virus which is taken from people who have already recovered from the disease. For the protection and future immunity against Covid-19, vaccines are vital. But making a vaccine with long-term immunity requires different stages of trial, which is going to take a while and it also involves regulatory hurdles as well. Meanwhile, plasma therapy can help treat the disease. But, confirmation of the antibody and its titer are essential before transfusing plasma.

Moreover, an antibody test may help to get a better insight on who might have developed a degree of immunity to SARS-CoV-2. If we know the recovery rate of Covid-19, it will be easier to protect the community by developing better strategies. A Covid-19 antibody seroprevalence study in Santa Clara County, California, showed that the number of infections is much greater than the reported number of cases. Antibody tests will enable authority to know the number of people who have immunity against Covid-19, which will eventually help them to decide how to deal with the virus and its management. Antibody tests will enhance epidemiological understanding of the virus's lethality, as well as its mode of spreading. Therefore, for understanding the dynamics of transmission and formulation of future strategy serological surveillance is essential.

From several pieces of research, we know antibodies may provide immunity to the SARS-CoV-2 virus. But there is no clear evidence about the long term effect of these antibodies and how long they protect us from future infection. In a study, researchers found IgG in 100 percent patients within 19 days after the onset of illness. Researchers got seropositive for IgG in 100 percent patients around 20 days after symptom onset in a different study.

Another study showed, 28th day after symptoms onset, IgG level decreases. Nothing can be said about the antibody's efficiency and how long it lasts in blood, based on these studies. Antibody tests, regular follow up, and surveillance studies on antibodies are required to know how long these antibodies may give us protection after natural infection. Antibody tests can provide information for better understanding if they can protect a person from reinfection. A study with 6 confirmed SARS-CoV-2 infected mothers and their infants found antibodies against SARS-CoV-2 though none of the new born babies were found infected with SARS-CoV-2. In most of the infants, IgG concentration was high, mostly during birth. Due to IgM's large macromolecular structure, usually, it is not transferred from mother to fetus. This type of study can play a significant role in enhancing the understanding of the serological characteristics of infants with SARS-CoV-2 infected mothers.

Antibody seroprevalence is important for a better and clear understanding of the case fatality rate as well as immune responses of the body. Many countries in the world have already carried out serosurveillance. These surveys are giving us valuable insights to monitor the progression of the pandemic by estimating the infection rates as well as identifying the true percentage of asymptomatic patients. Eventually, this information are being used to track how infections progress through the population over time.

Another important fact is, we can identify the genetic, environmental, nutritional and lifestyle factors that determine individual's antibody responses to SARS-CoV-2 by antibody surveillance. Seroprevalence surveys can also correlate immunity with risk factors for the disease, such as a person's age, location, or underlying health conditions. Additionally, serological surveys can be used to evaluate the vaccine effectiveness and the progression towards elimination. A high adaptive immune response is indicated by a strong neutralising antibody response. It is high time we knew how long the antibody can protect us following an infection while the silver lining of a potential vaccine against Covid-19 is getting prominent.

To study the duration of immunity, longitudinal serological studies that follow patients' immunity over an extended period of time will be required. Those results will be helpful for selecting a suitable vaccine for our population.

We must say, antibody seroprevalence study is not only essential for current pandemic rather they will play an important role in management and intervention of future epidemics. Therefore, Bangladesh government and health authority should take prompt steps to make Covid-19 serological kits available for research, surveillance and commercial purpose. So that the real scenario of Covid-19 infection can be unraveled to design mitigation strategies and we can also learn lessons for future challenges.

Bitali Islam, Research Assistant, BioTED.

Dr Muhammad Sougatul Islam, Founder and Director, BioTED.