The story so far: In the COVID-19 fight, the Indian Council of Medical Research (ICMR) had advised States to use antibody testing for surveillance and reiterated that the focus has always been on real time RT-PCR (or real-time reverse transcription-polymerase chain reaction) tests for diagnosis. The rapid testing kits that State governments had been using to detect antibodies to the novel coronavirus were throwing up unreliable results. In Rajasthan for example, rapid testing kits failed to detect antibodies even when the laboratories had confirmed patients to be COVID-19 positive.
What is the difference between rapid antibody tests and the RT-PCR tests?
There are two ways to detect the presence of a virus, directly or indirectly. Antibody tests, also called serological tests, have usually been the time-tested approach to finding out the presence of a virus in the body. They do so by detecting the presence and quantity of antibodies that are produced by the immune system to battle an infection. It is an indirect test because it cannot find the virus, but it can determine if the immune system has encountered it.
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Antibodies can show up between nine to 28 days after an infection has set in; by that time, an infected person, if not isolated, can spread the disease. Sometimes the antibodies may be produced in response to a closely-related pathogen and sometimes they may not be the right kind to counter the infection. These are the factors that can make an antibody test erroneous.
In an RT-PCR test, a nasal or throat swab is taken from a patient suspected of having the disease. The test involves extracting RNA or ribonucleic acid, the genetic material of the virus, and checking if it shares the same genetic sequence as the SARS-CoV-2 virus. If it is a match, the sample is deemed positive. The only way such tests turn negative is if the actual sample does not have the virus or the swab was not properly administered and too little of the virus was gleaned.
As the sequencing of genomes is now widespread and the technology well understood by experts in several countries, China, and subsequently others, were quickly able to determine the structure of the SARS-CoV-2 coronavirus and learn what differentiates it from related viruses. This is why it was possible to prepare accurate tests to detect the virus relatively quickly, almost in the middle of a pandemic, and the RT-PCR tests began to be followed as the ‘gold standard’ in detecting the virus. As not enough research hours have been spent studying the antibodies and the profile of recovered patients, the antibody tests we have for COVID-19 are imperfect.
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Why is there a clamour for antibody kits?
Antibody tests are fast and relatively inexpensive. The current RT-PCR technology requires RNA extracting machines, a specialised laboratory, and trained technicians. And at least a minimum of 30 samples are needed to make the process economically viable. The tests are done in batches and it can take up to four hours to confidently test for the presence of a virus from a batch. If one adds the time taken to isolate the RNA from swabs, this could again take a couple of hours. The scale of logistics involved can mean that it can practically take a day for results from a sample to be known. If one adds the cost of chemicals needed to perform these tests and the vagaries of importing practically every element of the paraphernalia involved, in the midst of a pandemic when demand far exceeds supply, it results in the test not being cheap. It can cost at least ₹4,500 depending on whether one is tested at a public or privately-run facility. Antibody tests are portable, can be administered on-site, conducted en masse and give quick answers. However, these answers are useful in-so-far as those who are using them are asking the right questions.
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What do antibody tests reveal?
Given that they are not useful for directly detecting the presence of the virus, antibody tests can be used to gauge the extent of infection in a community or a large group of people who may have had exposure to the virus. Much like pregnancy detection kits, rapid-test kits change colour when particular molecules are detected. Two kinds of antibodies result from an infection: Immunoglobulin M and Immunoglobulin G (IgM and IgG). In response to an infection, the IgM is first produced within a week of infection. Two weeks later, the levels of IgM reduce and are replaced by IgG. The latter is a longer-lasting antibody and, depending on the infectious agent involved, can offer different durations of immunity. Antibodies to the chickenpox virus last for decades. Those to influenza viruses and even other coronaviruses (that cause the common cold) last no more than a year or two. This is why people need flu shots at regular intervals, and one of the reasons why it is practically pointless to have a vaccine for the common cold. It is too early in the course of the COVID-19 pandemic to determine how long immunity lasts. Nevertheless the presence of IgM, IgG can in a sample of the population determine whether the virus is present in certain clusters. Ideally, this can help government authorities decide on what regions in a lockdown can be opened up if the aim is to get regular life back on track as soon as possible.
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This is what happened when infections had reached frightening proportions in the United States and Europe. It was apparent that the limitations of the RT-PCR combined with the virus’s ability to spread even through those who were not visibly sick would mean large numbers would be infected without being detected. Rapid antibody tests can also play a role in determining the degree of “herd immunity” in a population. That is, the true number who may have been infected; when a sizeable fraction of the population has been infected, the virus ceases its pace of spread. Current research expects herd immunity to have been achieved when 55% to 80% of the population has been infected — only careful serological surveys can establish that. Studies in India too have shown that for every symptomatic positive, there are two asymptomatic or presymptomatics (those who do not visibly manifest the disease). Thus, antibody tests could also be used for such estimates in India. The ICMR had laid out the strategy to use antibody tests to gauge the degree of COVID-19 presence in the country. The plan involved using a combination of both RT-PCR and antibody tests to establish infection levels.
What happened to India’s rapid testing plan?
Two Chinese companies, Wondfo and Livzon, got licences to sell 500,000 rapid antibody kits to the ICMR. Several of these were to be given to States and some were for the ICMR’s own use. A first batch was deployed in some States and soon complaints began pouring in over inaccurate results. The ICMR then asked States to stop using these kits for two days. After two days, the ICMR advised States to stop using the kits altogether. The Health Ministry has cancelled the licences given to the companies that were importing these kits from China. So far, the ICMR has not clarified what was wrong with the kits. The Chinese companies have also claimed that the kits were validated by the ICMR’s expert body, the National Institute of Virology (NIV). However, the NIV only clears batches of kits that are submitted for testing. It is possible that even if a company’s kits get cleared, it ends up supplying kits on the field that are not up to the mark.
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Another feature of the kits is their sensitivity (in percentage terms, the times the tests correctly identify people as positive for an infection) and specificity (in percentage terms, the times the test correctly rules out those not carrying the virus). Specificity refers to its ability to accurately distinguish between the target virus and other viruses. It is a well-established feature of tests that in regions of low actual prevalence of a disease, they can, depending on the kit’s specificity and sensitivity, miscategorise vast numbers of those tested. It is not clear if these were factored in in tests using kits blamed as faulty by States. India is not the only place where complaints over Chinese kits have been raised. The United Kingdom and Spain have also raised such issues with these kits. In either event, there is no clarity if the ICMR has ordered more kits. The Health Minister, Dr. Harsh Vardhan, has said that by the end of May, the country will have kits that are made in India for antibody and RT-PCR tests.
