Tuesday 21 April 2020

Coronavirus (8) Why is it difficult to have a high accuracy home-based antibody test?

In my last blog post, I mentioned about the technical problems that prevent the home-based antibody test from giving an accurate and sensitive result. Two of the reference articles I cited1,2 tell us additional reasons that make antibody tests for COVID-19 difficult to apply at this moment. This is precious knowledge that we cannot learn from textbooks but only from experienced experts. Let us have a closer look at what they said.

Thus far, it has been found that people infected with COVID-19 can develop different degrees of symptoms for the disease.3,4,5 Some can be seriously ill, while some can show little or no symptoms at all. Based on the patient samples analysed by research team of Dr. David Da-i Ho, a leading scientist at Columbia University in New York who invented cocktail therapy for HIV and is now leading a team to look for COVID-19 treatment, the patients with severe illness tend to develop a faster and stronger antibody response, while the ones with milder symptoms tend to develop the antibody response more slowly. This means that the one with severe illness will have a positive antibody test result at an earlier stage of the disease development compared with the one with milder symptoms, yet it is not possible to predict how long it's going to take for the body to develop enough antibodies to give a positive result in the antibody test. This highly variable immunity response across the population makes the development of a simple, reliable home-based antibody test considerably challenging. 1

Moreover, the level of antibody production for the asymptomatic or mildly symptomatic cases remains low even after two weeks of antibody response. This can result in only about half of the cases being detected. Additionally, it is still unclear whether the antibody level will increase if these people are tested one or two weeks later. Prof Marion Koopmans from the Erasmus University Medical Centre in Rotterdam did not think that the detection rate can reach the levels seen in severe cases. She said that the claiming of over 90% sensitivity by the home-based test is likely to be based on tests in patients recovering in hospital, who represent the most severe cases. Therefore, for the people with low or no symptoms, which accounts for about 80% of the cases, the sensitivity of the home-based antibody test will "end up around 50%-60%", which is highly unreliable.1

A shortage of blood samples from people recovered from COVID-19 is another reason that holds up the development of an antibody test. This convalescent blood is necessary for academia and industry to develop and validate the tests. The shortage is due to the administration in the UK making it difficult to get patient samples. "Access to patient samples has been a longstanding issue for the industry, and that is highlighted now when companies desperately need them" said Dr. Doris-Ann Williams, chief executive of the British In Vitro Diagnostic Association. The other reason for the shortage of convalescent blood is simply because the disease is newly emerged. "People can have two weeks of disease and then three weeks to mount this antibody reponse, but if you look back five weeks or so, there was hardly anyone in Britain with the disease" said Prof John Bell from Oxford University.2

From these experts in the field, we now understand that the big range in immune response for a disease seen across the population makes it difficult to develop a simple home-based test which is reliable over an entire population. The shortage of blood also hampers the development and validation of the antibody test. As the problem arising from a wide range of immune response can never be changed, and the shortage of blood for antibody development will not be solved in the near future, I would not recommend the use of antibody test to check the history of infection of a person. The false results could be disastrous.


References

1. "Coronavirus 'game changer' testing kits could be unreliable, UK scientists say" The Guardian news, 5th April, 2020. https://www.theguardian.com/world/2020/apr/05/coronavirus-testing-kits-could-be-unreliable-uk-scientists-say
2. "UK COVID-19 antibody tests not ready until May at earliest" The Guardian, 8th April, 2020. https://www.theguardian.com/society/2020/apr/08/uk-covid-19-antibody-tests-not-ready-until-may-at-earliest
3. Qian G, Yang N, Ma AHY, et al. A COVID-19 Transmission within a family cluster by presymptomatic infectors in China. Clin Infect Dis 2020. Epub March 23, 2020.
4. Du Z, Xu X, Wu Y, Wang L, Cowling BJ, Meyers LA. Serial interval of COVID-19 among publicly reported confirmed cases. Emerg Infect Dis 2020. Epub March 19, 2020.
5. Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility-King County, Washington, March 2020. MMWR Morb Mortal Wkly Rep 2020. Epub March 27, 2020.

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