How accurate are the three types of tests for Covid-19?


  • Wellness
  • Tuesday, 09 Jun 2020

This image provided by the US National Institute of Allergy and Infectious Diseases shows the SARS-CoV-2 virus (orange) emerging from the surface of normal cells (green) cultured in the lab. An antigen test detects the proteins of the virus in a person’s blood, but needs to be followed up with a PCR test for a confirmed diagnosis. — Photos: AP

Although much is known about tests for the SARS-CoV-2 virus that causes Covid-19, there is much more that is still unknown.

Prior to discussing the accuracy of these tests, it is important to know about the sensitivity and specificity of all tests, the infectivity of the SARS-CoV-2 virus and the body’s antibody response.

Sensitivity and specificity

The reliability or accuracy of any test depends on its sensitivity and specificity.

Sensitivity refers to how often a test correctly produces a positive result for people who have the condition tested, i.e. the “true positive” rate.

A highly sensitive test will detect almost everyone who has the condition and will not produce many false negative results, i.e. a negative result for someone who actually has the condition.

Specificity refers to how often a test correctly produces a negative result for people who do not have the condition tested, i.e. the “true negative” rate.

A highly specific test will detect almost everyone who does not have the condition and will not produce many false positive results, i.e. a positive result in someone who actually does not have the condition.

This is illustrated by pregnancy tests. Take for example, a pregnancy test with a sensitivity of 98% and a specificity of 98%.

This means that for:

  • Sensitivity: 98 out of 100 pregnant women will be correctly identified.
  • Specificity: 98 out of 100 women who are not pregnant will be correctly identified.
  • False negative: Two out of 100 pregnant women will not be correctly identified.
  • False positive: Two out of 100 women who are not pregnant will not be correctly identified.

Infectivity of the coronavirus

A lab technician adds vials with patient specimens to a PCR machine. The PCR test remains the best way to confirm Covid-19. — BloombergA lab technician adds vials with patient specimens to a PCR machine. The PCR test remains the best way to confirm Covid-19. — Bloomberg

There are many gaps in the knowledge about the body’s response to the SARS-CoV-2 infection.

A person’s response to the initial infection depends on the viral dose (amount of virus) received, the person’s genetic background and their immune system’s programmed response to new infections.

These are influenced by the person’s general health and age, which appears to affect the severity of the disease.

Generally, the body’s immune system fights back against any infection by a microorganism by producing proteins called antibodies, which bind to the microorganism and either renders it harmless or identifies it for destruction by the body’s immune cells.

Antibodies usually stay around for some time after an infection.

When reinfection by the same microorganism occurs, the body’s immune response is much faster.

Covid-19 patients are usually the most infectious one to two days before the onset of symptoms, with their infectivity declining thereafter.

Clinical evidence has shown that patients are generally non-infectious from day 14 of illness (hence the quarantine period of 14 days in Malaysia).

In clinical practice, the onset of illness is defined as the date when the symptoms are reported by patients who experience them, the date of the first positive real-time polymerase chain reaction (PCR) test or seven days before first positive serology test for asymptomatic patients (i.e. those without any symptoms).

The amount of virus in the body increases initially, reaches a peak, then declines.

The antibodies in the blood can be found between five to seven days after infection and increases as the amount of virus declines.

Covid-19 tests

There are two types of tests for Covid-19: PCR tests and serology tests.

PCR tests detect viral ribonucleic acid (RNA), which is present when the person is actively infectious.

It is done by taking samples from the nasopharynx, throat or the lower respiratory tract – the collection of which is not always easy.

This test is the one currently used for diagnosis.

A positive PCR test means that the person is shedding virus and can spread the infection to others.

However, this test cannot determine if a person had a previous Covid-19 infection.

It also does not help determine whether persons who have been exposed to SARS-CoV-2 will develop Covid-19 in the two weeks after exposure.

The PCR test requires complex laboratory equipment and usually takes several hours, or even days, for the results to be available.

The accuracy of the test depends on how and when the sample is taken. The sensitivity depends on when the test is carried out.

In a literature review of false negative results published in the Annals of Internal Medicine on May 13 (2020), the authors found that: “Over the four days of infection before the typical time of symptom onset (day five), the probability of a false-negative result in an infected person decreases from 100% on day one to 67% on day four.

“On the day of symptom onset, the median false-negative rate was 38%.

“This decreased to 20% on day eight (three days after symptom onset), then began to increase again, from 21% on day nine to 66% on day 21.”

Because of the risk of false negative results, the diagnosis of Covid-19 is not dependent on a single test.

The antigen test identifies viral proteins from those currently infected and provides results within a few minutes.

Its accuracy has not been studied as much as those of PCR tests.

As such, a positive result from an antigen test has to be followed up with a PCR test to make a diagnosis.

The sensitivity and specificity of antigen tests are varied.

Meanwhile, serology tests detect antibodies to Covid-19 infection.

The test does not identify anyone who is currently infectious.

It is usually done by taking a blood sample that is analysed by different techniques.

The type of technique determines the time taken to get a result.

The test is not for diagnosis or to prompt an individual to get further tested for a confirmed diagnosis.

Rather, it provides information about infection rates in the community where errors in an individual result have less impact.

Some serology tests may cross-react with that of other coronaviruses like the ones that cause SARS (severe acute respiratory syndrome) or MERS (Middle Eastern respiratory symdrome), leading to false results.

Serology tests with low sensitivity and specificity will not produce reliable results.

The World Health Organization (WHO) has a list of serology tests used by its member states; however, it should be noted that none of these tests have been endorsed by the organisation.

Serology tests, an example of which is seen here, are not meant for individual diagnosis, but rather to check the infection rates of Covid-19 in a community.Serology tests, an example of which is seen here, are not meant for individual diagnosis, but rather to check the infection rates of Covid-19 in a community.

Be aware of limitations

The standard operating procedure of the National Security Council requires workers in certain economic sectors to have mandatory tests for Covid-19.

The assumption that someone with a single negative test is not infectious is flawed.

Any test carried out is only reflective of the individual’s condition at the time of testing.

While PCR tests can usually determine whether a person is currently infectious, they are not 100% accurate as false negatives vary from 20% to 100%.

Meanwhile, a positive rapid antigen test requires a follow-up PCR test.

And serology tests detect whether antibodies have been produced in response to an infection and cannot determine whether a person is currently infectious or has been recently infected, i.e. in the past week or so.

In addition, no serology test has been endorsed by WHO.

It is important that policymakers, employers and the public be aware of the limitations of Covid-19 tests.

A discussion with the attending doctor is advisable for those undergoing these tests.

Dr Milton Lum is a past president of the Federation of Private Medical Practitioners Associations and the Malaysian Medical Association. For more information, email starhealth@thestar.com.my. The views expressed do not represent that of organisations that the writer is associated with. The information provided is for educational and communication purposes only and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.

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