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Testing for the new coronavirus

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There are two types of test for COVID-19. One detects the genetic code of the virus and is used to diagnose current infection. The other detects antibodies to the virus and is necessary to pick up past infection. There is a need for faster and easier tests of both kinds.

An ideal test is cheap and easy to do and returns results quickly. It should accurately identify those who have a disease (i.e. be sensitive) but also those who do not have it (i.e. be specific).

Detecting the genetic code of the virus

This type of test uses swabs from the nose and throat. These are sites in the body where the virus is most likely to be found. Tests need a relatively large amount of virus RNA, but swab samples only contain a tiny amount. This problem is overcome using a technique called the polymerase chain reaction (PCR).[1][2] In a few hours, PCR makes millions of copies of the genetic code of the virus, starting from the tiny amounts on the swab. The test is positive if it identifies a sequence unique to the new coronavirus.

These tests are the best way to check whether someone’s symptoms are due to COVID-19 or caused by something else. They are used in health services to diagnose current infection.

They are rapid (about 6 hours), sensitive and specific but samples need to be sent away to specialist laboratories, delaying results.

Detecting an immune response to the virus

Antibodies are produced about 5–7 days after a coronavirus infection as part of the immune response.

If a person has antibodies, it might be because of a recent and active infection, or because they had SARS-CoV-2 infection in the past, which in many cases may have been asymptomatic. If a sick patient is tested before they have developed antibodies, they will test negative, despite having an active infection.

Antibodies typically persist at measurable levels for many months or years after viral infections. So, antibody tests are best used for surveys trying to find out how many people have been infected by SARS-CoV-2. This number may be much larger than the number of cases identified by hospitals. This gives more accurate information about the extent of disease spread in a population.

Antibody tests are also important because they can identify healthcare workers and others who have had infection in the past. These people are likely to be at very much reduced risk of becoming reinfected if exposed to people with active infection. Because of this they should be able to care more safely for those with active infection than staff who have not yet had the infection.

It seems likely that this immunity may wear off over time (many months or years). It is also possible that the virus will evolve by mutating to a new strain that can escape the immune response to earlier strains. This is another reason why vaccination is so important and why a vaccine, once found, may need to be updated regularly, as is the case for flu vaccines.

Types of antibody test

Two types of test are used on blood samples. The first uses proteins from the virus that are known to provoke an immune reaction. A thin layer of this protein is put into wells in a plastic tray. If there are antibodies present in a person’s blood sample, they will attach themselves to the protein in the wells. The chemical reaction between the virus protein and antibodies signals the presence of antibodies, revealing that this person is infected, or has previously been infected, with the virus.

This test is rapid and can be undertaken at the bedside or at a GP surgery (called a ‘point of care’ test). It is usually not highly sensitive and specific, so may give a few incorrect results.

The second type of test uses antibodies from patient blood samples in ‘neutralisation’ tests. If those antibodies can protect human cells in the lab from coronavirus infection, the patient has previously had the infection themselves. These tests take several days but are more specific.

What is needed

Hospitals need tests that are quicker and more accurate. Portable rapid PCR machines are available, giving results within an hour, but they are not yet adapted for widespread testing of COVID-19. Tests are also being developed to detect antibodies to the new coronavirus more rapidly, easily and accurately. All are at an early stage of development.[3][4]

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References

  1. Coronavirus disease (COVID-19) technical guidance: Laboratory testing for 2019-nCoV in humans. World Health Organization. 2020 Mar.

  2. Corman VM, Landt O, Kaiser M, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveillance. 2020 Jan;25(3) DOI: 10.2807/1560-7917.ES.2020.25.3.2000045.

  3. Zhang W, Du RH, Li B, et al. Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes. Emerging Microbes & Infections. 2020;9(1):386-389. DOI: 10.1080/22221751.2020.1729071.

  4. Normile, D. Singapore claims first use of antibody test to track coronavirus infection. Science. 2020 Feb 27.

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