April 17th, 2020

Buying Rapid Test Kits from China

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This is part of the series of posts on buying medical supply from China
Part I – Buying KN95 masks from China
Part II – Buying surgical masks from China
Part III – Buying Ventilators from China
Part IV – Medical supply from China and my role
Part V – Buying Rapid Test Kits from China
Part VI – Yiwu market shutdown for medical supply

From time to time, I get requests to find COVID-19 test kits from China. I have mostly avoided previously because I do not think I am qualified to handle it. And true enough, there are a number of reports that test kits from China are unreliable.

As time goes by, as countries are trying to get back to normal, extensive testing becomes important as I get more and more requests. I have also learned more about these test kits talking to the factories (including Wondfo, Innovita, Livzion and Bioda to name a few), industry experts and doctors from around the world. 

Now that I have a better understanding of how it works, I become convinced that there is a misunderstanding of rapid antibody test kits and particularly how to use it as a matter of public policy.

TL:DR Version : Rapid Antibody test kit is not a silver bullet to rapidly diagnose large numbers of people. It is not a 10 minutes answer to whether you have COVID-19 or not, like a pregnancy test. It is also not ready to be a DIY home test kit. 

To test for COVID-19, there are generally the following methods: RNA testing, nucleic acid test, antigen test, antibody test and CT-Scan (or maybe there are some other methods which I am not aware of).

Apr 19 Update: There are two ways to test for SARS-CoV-2 infection. The first is to look for the virus itself, and the second is the immune response, the antibody produced in response to the virus. To look for the virus, we need to look for genetic RNA of the SAR-CoV-2 virus. This is done by nucleic acid application tests, or “NAAT” tests, which are molecular tests that detect the virus’ genetic material. To look for the antibody, we need to do serology test that detects different type of antibodies, the most IgG and IgM. In some countries, CT lung scans have been used to help identify COVID-19 patients. This is because existing nucleic acid and antibody tests are not 100% accurate to identify every single patient.

Inputs from Dr Chong Kian Tai. Thank you!

Laboratory testing uses a combination of these methods to get to a diagnosis. The problems are they are slow (a few days to get results) and expensive (hundreds to thousands of dollars). If you want to test a large number of people, this is not a viable option. 

Even if you use the most intrusive sample collection (tracheal aspirate procedure, collecting samples from your lung) or most expensive blood RNA testing, you would still not be able to correctly diagnose very early infections. 

To curb the the unauthorised medical supplies from factories in China, MOFCOM Regulation No. 5 only approves 23 test kits products from China to be exported: 15 types of nucleic acid test kits (qf-PCR or others) and 8 rapid antibody IgG/IgM (Colloidal Gold Method). All of them are not expensive, between $4 to $10 per test.

Nucleic acid tests typically require a nasal swab by healthcare professionals and then tested or cultivate on a specialized cassette for a few hours (sometimes up to 24 hours) before you get a result. The objective is to determine the presence of the SARS-CoV-2 (the coronavirus that causes COVID-19). 

Photo from KOB4

When doing a nasal swab, if it did not go far enough into your nose (see correct location from the picture above) to where the virus resides, you might get a false negative because of bad sampling error. It is also not able to detect early infections, when the initial virus load is minimal or if the virus still growing in your lung and not enough virus is in the back of your nose. Therefore, negative tests of SARS-CoV-2 by this testing method does not guarantee you are not infected. 

What caught most people attention is the rapid antibody IgG/IgM serology test. With a drop of blood, you can get a “result” within 10 minutes. (See FAQ on Diagnostic Testing on FDA website w.r.t serology testing)

What antibody IgG/IgM indicates are the two kinds of antibodies in your blood that occurs if you have been exposed to the SARS-CoV-2. It tests the presence of the antibodies. The lack of it indicates you are not infected. It is like the opposite of the nucleic acid PCR test. 

A lot of people imagine this is a solution to test a large number of the people within the city; or a office or factory could administer the test to quickly screen infected workers; or the airport could screen incoming travelers before they are allowed into a city. 

But the answer is far more complicated. While this test may say you do not have the antibody and therefore suggest you are not infected, it could be a false negative because you might be at the early stage of infection called the latent period (between 5 to 14 days) where you have no symptoms and therefore your body has not started to generate the antibodies yet. 

Some may naively think, “What if I intentionally catch COVID-19 so that my body will have the antibody. The test would indicate I have the antibody against SARS-CoV-2 and therefore I am safe.” (Update: WHO warning: No evidence that antibody tests can show coronavirus immunity)

The answer is no. If you have IgG positive and IgM negative does not imply you have completely recovered from the disease. You could still be infectious and a carrier. We have to do a nucleic acid PCR test as well to get to the diagnosis. This is why serology test is only a complementary test, that need a licensed healthcare professionals to do a clinical assessment and confirmatory nucleic acid PCR to check for any remaining SARS-CoV-2.

What if both IgG and IgM are positive? It means you could be (a) actively infected with SARS-CoV-2; or (b) recovered from COVID-19 but infected by another type of coronavirus; or (c) recovered from COVID-19 but your body IgM counts have not gone down yet. In order to get a clinical diagnosis, we also need to do a nucleic acid PCR test.

Put it simply, the IgG/IgM antibody rapid serology test can be used to determine if you have never been infected by SARS-CoV-2, but only if you do it once every 10-14 days. 

Once you got SARS-CoV-2 infection, the antibodies serology test is useful as a complementary test, in addition to nucleic acid test as well to get to the right diagnosis. 

We haven’t even taken into consideration the reliability of these rapid test kits, which due to techniques and manufacturing quality, may have a sensitivity and specificity of 85-99%, even assuming they are not faulty or fakes.

If we have to do a nucleic acid PCR test in combination with IgG/IgM antibody test, why bother with the latter? Because nucleic acid PCR test is also unreliable by itself so we need to do two different, and sometimes a third one, to get to a diagnosis. Sometimes you may even have to wait for a few days in between to test again to be certain.

Photo from UK Research and Innovation

What we need is an accurate simple non-intrusive rapid test kit that can do early detection. This is what a lot of politicians and government officials assumed the rapid antibody test kits would be. They became very disappointed when it did not deliver. 

The ideal accurate rapid non-intrusive test kit that can do early detection without false positive or false negative that you can do at home, unfortunately, does not exist yet.

Update: Government officials and politicians, please stop promising your people that there is a DIY at home test kits (“Prime Minister Boris Johnson has likened coronavirus antibody tests to pregnancy tests as they are simple, providing a quick response.“) then turn around the blame the test kits. Read the fine prints, or if you are the Prime Minister, listen to your Surgeon General advices. I am not trying to defend Chinese made test kits. Antibodies test kits made by any country (e.g. South Korea) would be similar.

Note 1: China also have rapid antigen test kits but none of those are allowed to be exported. I will cover it when I have more information on that. It is said its sensitivity and specificity is around 30%.

Note 2 : For public health policy makers on the use of Rapid Antibody Test kits on a group of people (e.g. on a cruise boat), here is how it might work.

  1. You use rapid test on everyone and depending on the test result, isolate them differently:
    1. Group 1 – both IgG/IgM negative (clean);
    2. Group 2 – IgG positive / IgM negative (maybe infected);
    3. Group 3 – IgG both IgG/IgM positive (likely infected); and
    4. Group 4 – IgG negative / IgM positive (likely early infected).
    5. Group 5 – Confirmed infected group
  2. On Group 1, you repeat the test every few days until there is no new suspect cases. Then Group 1 is cleared.
  3. On Group 2, you do a PCR test on them to determine if they are still infected. If they are, you may do another third test before put them in Group 5. If they are not, then you keep them in Group 2 (repeating the tests every few days) and allow them to leave after 14 days of isolation.
  4. On Group 3 and 4, you do a PCR test on them to determine if they are infected. If they are positive, then place them into Group 5 . If they are negative, then you keep them in their original group (Group 3 or 4) and then repeat test again after a few days, until you can asserts they are safe to leave or goes to Group 5.
  5. on Group 5, you have to isolate them and provide medical care for them until they are cured.

When politicians say we need to test and test, and health officials say we need millions of tests, this is what they meant. Very complicated but that’s what we have to live with in the future.

If we start grouping people in the society in this manner, we might see a new “caste system”, and who you can have social interactions or distance would depends which Group you are in. I pray we will not come to that. Keep safe and healthy everyone.

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