Why do false positives occur and what does this mean for mass Covid-19 testing?

False positives and negatives occur as there is a margin of error in all Covid-19 tests. PHOTO: ST FILE

SINGAPORE - Royal Caribbean International's cruise ship, Quantum of the Seas, returned to Singapore on day three of a four-day cruise after an 83-year-old man on board tested positive for Covid-19.

The man was taken to the hospital on Wednesday afternoon (Dec 9), where further tests were conducted. That same night, the Ministry of Health said the man's original sample was retested at a national laboratory and returned negative for Covid-19 infection.

A second fresh sample tested by the lab also returned negative on Wednesday, while a final confirmatory test on Thursday showed the man did not have the coronavirus, indicating that his test result on board the ship was a false positive.

The Straits Times looks at what false positives are, how likely they are to occur, and how testing capabilities on board cruise liners differ from that of national laboratories.

Q: What is a false positive or false negative test result, and why do they occur?

A: A false positive test result means that a person without the infection is wrongly diagnosed as infected, while a false negative means that a true infection is missed. False positives and negatives occur as there is a margin of error in all Covid-19 tests, and none are able to accurately diagnose Covid-19 infections all of the time.

Q: How likely are false positives or negatives?

A: Two measures are used when discussing the accuracy of Covid-19 tests: sensitivity and specificity.

Sensitivity refers to a test's ability to identify those infected as positive. A test with lower sensitivity will have more false negatives, meaning more true infections are missed.

On the other hand, specificity refers to a test's ability to correctly identify those not infected as negative. This means that a test with lower specificity has more false positives.

The default test used in national laboratories is the polymerase chain reaction (PCR) test. It has a sensitivity rate of more than 93 per cent, and a specificity rate of more than 95 per cent, but can take up to one or two days for results to be out.

Antigen rapid tests, as the name suggests, is faster with the results, taking only about 15 to 30 minutes for results to be ready. These have been used for testing before large-scale events, and have a lower sensitivity rate of 82 but a specificity rate of 99 per cent.

Q: Could the same test sample yield different results?

A: Yes, and for several reasons.

First, because of the varying sensitivity and specificity of each type of Covid-19 test, subjecting the same sample to different testing protocols can give different results. Professor Teo Yik Ying, dean of the National University of Singapore's Saw Swee Hock School of Public Health, said it is possible that the testing regime in some corporate settings may utilise point-of-care tests or antigen rapid tests, which are able to deliver a result faster but tend to have a higher error rate.

As a result, it is entirely possible for some of the less accurate protocols to yield an erroneous finding when the same sample is tested using different testing protocols.

Second, the coronavirus enzymes that might be present in a person's swab sample are susceptible to degradation in the hostile external environment, said infectious diseases specialist Leong Hoe Nam. So a sample which tested positive earlier may test negative in subsequent tests.

Q: What are the testing capabilities on board cruise ships, and how do they differ from tests in national laboratories?

A: Mr Michael Goh, head of international sales at Genting Cruise Lines and president of Dream Cruises, said last month that its safety regime includes a new real-time PCR machine on board that yields Covid-19 test results in 60 minutes while being able to rule out 22 other respiratory viruses such as H1N1 and influenza.

Similarly, Royal Caribbean says on its website that "rapid Sars-CoV-2 tests can be conducted right on board in our medical lab that allows for rapid, accurate on-site RT-PCR testing with results in under an hour, alongside a multitude of other evaluative tests".

While Dream Cruises and Royal Caribbean did not reveal the sensitivity and specificity rates of the testing machines on board their ships when asked, Mr Goh on Thursday said the PCR machine on board World Dream was approved by the Health Sciences Authority, and that PCR tests "remain the most accurate test available today".

A polymerase chain reaction testing machine on board the Quantum of the Seas cruise ship. PHOTO: ST FILE

Dr Leong said the accuracy and precision of the machines on cruise ships are likely to be lower than that of the Health Ministry's laboratories.

Describing machines used in outstation situations as "very optimal" for such situations, Dr Leong said they likely yield "quick and dirty" results, and lack the technical expertise of more accurate machines, that are larger and difficult for ships with space constraints to accommodate.

Despite the testing machines' potential lack of accuracy when compared with regular PCR tests, Dr Leong said it was still a good idea to have such "standalone" machines on board cruise ships for screening of suspected Covid-19 patients.

Q: What does the likelihood of false positives mean for mass testing as large-scale activities resume progressively?

A: With no test able to be completely accurate, experts said it is important to learn how to cope with the reality of these errors occurring in tests.

Prof Teo said: "The reality is that, as testing becomes more prevalent, erroneous results will emerge.

"These will have knock-on effects on whether a traveller is incorrectly denied entry or participation, or whether someone who is genuinely infected is missed and ends up seeding additional cases in the community.

"For observed positive findings, especially when diagnosed with rapid or point-of-care tests, it may be worth undergoing a round of retesting, preferably with an independent testing protocol to avoid any systematic errors.

"This way, we avoid the false scares that can happen, such as what happened on the Royal Caribbean ship."

The Quantum of the Seas has intensive care units and isolation rooms that are fully equipped with ventilators and other medical supplies. ST PHOTO: GIN TAY

Dr Leong said that retesting capabilities may not be present on board ships, as they are usually done with lab experts in consultation with infectious disease experts who have assessed the epidemiological risks of the positive case. As a result, he said the captain's decision to turn back on Wednesday morning was prudent.

Adding that false positives will continue to occur as testing becomes more widespread, Dr Leong said patience on the part of the patients is important as repeat swabs and lab tests will be required when they occur.

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