Some questions about COVID-19 antibody testing kits

Sheikh Mohammad Fazle Akbar and Mamun Al Mahtab
Published : 3 May 2020, 03:19 AM
Updated : 3 May 2020, 03:19 AM

Nearly 2.5 million people have so far been infected with the novel coronavirus across the globe, and about 250,000 of them have died from COVID-19, the respiratory illness caused by the virus, but still there has not been any specific treatment or vaccine.

As of today, the diagnosis of coronavirus infection is accomplished mainly by reverse transcription-polymerase chain reaction or RT-PCR kits using samples collected from the respiratory tract. This method looks for the coronavirus itself in the specimens.

Recently, some other methods have been developed for inducing insights into its epidemiology. These include rapid diagnostic test or RDT which detects antibodies – Immunoglobulin M and G or IgM or IgG – in serum, saliva and nasal swab, and enzyme-linked immunosorbent assay or ELISA testing of whole blood, plasma and serum also for the assessment of IgM or IgG.

Please note that a test for a virus during an outbreak has to be judged as to whether it is a diagnostic test or a test for studying seroprevalence and epidemiological aspects of the virus.

Bangladesh's Gonoshasthaya Kendra has invented testing kits which, it claims, can detect the novel coronavirus by looking for antibodies and antigen in the blood very fast.

It's good news and if these kits are intended for developing epidemiological insights about the coronavirus, we would be reluctant to make any discussion at this point when the kits have headed for trials. However, if the kits are for diagnosis of COVID-19, several questions should be addressed before the kits become available for usage.

First and foremost, it must be clarified whether these kits will be used as a diagnostic tool for coronavirus patients as it is done through RT-PCR at this moment around the world. As reported by mass media, the private organisation has claimed its kits are highly sensitive. In fact, they have gone on to claim that these are more sensitive than the well-established RT-PCR method! To validate their claims, the authorities should compare in-house validation with the results from RT-PCR kits.

If respiratory samples are properly collected and the RT-PCR machine is properly run, the result is supposed to be 100 percent accurate. But, considering the fact that the majority of patients develop antibody response only in the second week after onset of symptoms, the Gonoshasthaya Kendra needs to clarify how its kits are more than 100 percent accurate even before antibodies are created in a patient's body.

Moreover, studies suggest SARS-CoV-2 can be found in the blood of merely 1 percent COVID-19 patients, although one recent scientific publication has stated that the viral RNA has been detected in 41 percent sera. So, the question that logically comes to mind is how the Gonoshasthaya kits can detect the virus antigen in the blood of 100 percent patients, a data that has never been elucidated before. This unique data should be validated in a properly designed study with positive and negative controls.

These realities and circumstantial evidence indicate that the scientific community would also like to know the sensitivity and specificity of their antigen and antibody kits. Is there any paper submitted for peer review with the detection system of these kits?

The million-dollar question, however, is whether the antigen used in these kits is patented or not. If it is patented, would the Gonoshasthya Kendra please provide the number? If it is not patented or if they have decided not to apply for patents, our request to them is to provide the amino acid sequences of the antigen that has been used for coating the kits.

At least on one occasion, the Gonoshasthaya Kendra has informed the media that they imported the "antigen" from abroad for in-house validation of their kits. Since they have claimed to be the "inventors" of the antigen, how is this antigen commercially available in the world market?

Since advanced centres in the US, Japan and Europe have so far failed to characterise the diagnostic antigen of the novel coronavirus despite tremendous efforts, this information will help mankind all over the world, not only to diagnose the disease but may also to develop an effective vaccine within a short time. One such example is the discovery of surface antigen of hepatitis B virus by Professor Baruch Samuel Blumberg. That won him the Noble Prize in 1976.

Apart from these scientific concerns, there are some regulatory factors for drug and kits development. The development and registration of kits depend on the law of the land. This convention applies to all countries of the world. It is not only applicable to Bangladesh, but also to any country in the world and these steps are not usually bypassed. It is a real-time experience that we see in the US, Italy or Spain today where the use of such kits for diagnostic purpose led to a disastrous outcome. Not only so, in the not too distant past Spain and the Czech Republic had to return imported Chinese kits and very recently India suspended the use of locally developed kits as there were yielding bizarre results.

The entity, utility, merits and demerits of these kits are a matter of scientific interest and more importantly kits of this nature place these for the greater interest of mankind. Therefore, serious discussion and evaluation are a must. We would request the Gonoshasthaya Kendra to come forward with:

(1) relevant data regarding antigen, patent, or publication so that the scientific values of the kits are exposed;

(2) Validation data regarding sensitivity and specificity of the kits;

(3) Data regarding the comparison of their kits with RT-PCR kits;
(4) The status of the patent of their kits;

(5) Publication of their data in a peer-reviewed journal.

The entire facts regarding the kits developed in Bangladesh is a matter of scientific interest that involves life and death. The kits in question should be evaluated from the point of scientific judgement, whether it is prepared by our countrymen or other scientists. However, something developed by Bangladeshi scientists may receive favour for prompt action within the scientific arena.

Finally, we would remind with all the warriors in the fight against COVID-19 that Bangladesh, as well as the world, have been facing an epidemic with mounting morbidity and mortality. Naturally, the entire mankind is neither in a position to discard a 100 percent effective sero-evaluation system for diagnosis of SARS-CoV-2, nor can we waste time after an illusion that is not evidence-based and purposeless.

*All queries and references related to this article can be sent to Sheikh Mohammad Fazle Akbar at sheikhmohammadfazle@gmail.com

*One of the writers had raised some of these questions in an interview with bdnews24.com: Scientist questions Gonoshasthaya Kendra's COVID-19 testing kits

* Read the writers' previous article on antibody testing kits: Test, test and test – what's the best?

Sheikh Mohammad Fazle Akbar is a researcher at the Ehime University in Japan. Mamun Al Mahtab (Shwapnil), a hepatologist, is currently working as the chairman of the Hepatology Department at the Bangabandhu Sheikh Mujib Medical University.