Why the Covid-19 antibody test quality matters

According to John Hopkins University, there are more than three million confirmed Covid-19 cases globally and more than 2.2 lakh deaths. The world economy is bearing the brunt of maintaining social distancing, isolation and lockdown. People are losing jobs as an aftermath.

To come out of this situation, many countries are trying to establish a new concept; "immunity passport" or immunity certificate. This will guarantee that individuals have antibodies for SARS-COV-2, which cause COVID-19, and may be permitted to step out of the lockdown.

The assumption is that an individual who has recovered from SARS-COV-2, is an asymptomatic individual or has exhibited mild symptoms are immune to future re-infection and thus could be permitted to return to work and travel - a step towards normalizing the pandemic. Countries such as Germany, Italy, Britain and Chile have considered this idea.

However, WHO warns in its latest scientific brief that there is currently no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection. To why WHO is saying this, we have to look at the basics of immune system and test quality parameters that may impact accuracy and reliability.

When we are attacked by pathogens such as virus, bacteria etc., our immune system naturally fight the pathogen in three steps. Firstly, the body makes initial defense to a viral infection with a non-specific mechanism called innate response, in which some cells of the immune system called macrophages, neutrophils, and dendritic cells, participate and slow the progress of virus and may even prevent it from causing symptoms.

Secondly, this non-specific response is followed by an adaptive response where the body makes antibodies that specifically bind to the virus. These antibodies are made from proteins called immunoglobulins. The process of antibody production in case of covid-19 takes one to two weeks.

Thirdly, the body also makes T-cells that recognize and eliminate other cells infected with the virus. This is called cellular immunity. These combined adaptive responses may clear the virus from the body, and if the response is strong enough, may prevent progression to severe illness or re-infection by the same virus. This process is often measured by the presence of antibodies in blood. There are several types of antibodies but usually two types of antibodies are measured, IgM (Immunoglobulin M) and IgG (Immunoglobulin G), to check immunity.

Multiple coronavirus antibody tests are now available worldwide, including in rapid and automated instrument platforms format. Anti-body tests are sometimes referred to as serology tests also.

US Food and Drugs Administration (FDA) is giving emergency authorization of these test methods, CE marking (in-vitro diagnostic) is also going on in European countries. While there are some quality tests, WHO is still not satisfied with the quality of these tests and recommends increased accuracy and reliability.

However, unreliable tests can produce false negative and false positive results. In terms of covid-19, both are alarming.

False negative result will lead to the infected individual spreading the infection without knowing they are infected. False positive result increases the likelihood of the individual being susceptible to infection.

How can antibody tests give false result? According to WHO, apart from SARS-COV-2 coronavirus that is causing Covid-19, there are six other common corona viruses.

The antibody tests are not always able to distinguish between these viruses. If people are infected by any one of these common corona viruses, they may produce antibodies that cross-react with antibodies produced in response to infection with SARS-CoV-2 while testing.

These reflect in tests' quality parameters such as sensitivity and specificity.

A 100% sensitive test means the test does not give any false negative result and 100% specificity tests mean the test does not give false positive result.

But in real-world, getting 100% sensitive and specific test is very difficult but near about 100% is possible and acceptable.  

For example, if a test sensitivity is 95%, there is a chance that five out of hundred individuals will produce false negative result. Which means these five individuals will spread the diseases without knowing their status. In case of specificity, this is vice versa.

Scientists have also questioned the durability of immunity because there have been reports, including from China and South Korea, of patients who appeared to have recovered from the disease, testing positive again.

Now the question is whether antibody tests are useful or not, because many countries are now testing for coronavirus antibodies at the population level or in specific groups, such as health workers, close contacts of known cases, or within households.

According to CDC (Center of Diseases Control and Prevention, USA), antibody test results are imperative for detecting infections with few or no symptoms.

These tests are also important in plasma donation and to find out population risk factors and surveillance.

NIH Director Dr. Francis Collins mentioned that SARS-CoV-2 antibody tests are just in the development stage. Hopefully in the near future the kit

manufacturers will develop highly accurate and reliable antibody tests to detect and contain Covid-19.

The author is a biochemist