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expert reaction to COVID-19 testing for incoming travellers

There have been questions from journalists about COVID-19 testing at airports in the UK for incoming travellers. 

 

Prof Terry Wilkins, a Fellow of the Royal Academy of Engineering and Emeritus Professor of Nanomanufacturing Innovation at the University of Leeds, said:

On the Science and Technology:

“The RNA/DNA PCR tests measure active virus in the throat mucous and hence will give a positive results several weeks before the antibody Ab tests which are performed on blood serum. This would be key for airport arrivals testing.  The use of PCR  gene amplification plus secondary biochemical amplification e.g. chemiluminescence etc to quantitate the amplified DNA will ensure this method is the most sensitive – detecting vanishingly small quantities of virus RNA!

“The test consists of 2 parts i.e: a) sample taking with a swab of the tonsils and b) the gene amplification.  The second stage is easily automated, reliable and quick taking as little as 2-10 minutes.  Good examples of this are the Oxford University/Suzhou U collaboration or the Taiwan test by Prof Jiunn-Der liao.  The sample swab operation is the weakest link in these tests and could present the most error.  It is normally manual and the RNA has to be released by enzyme treatment.  The latter could easily be automated and I am aware of groups in Europe doing this. 

“The Antigen (Ag) test is an alternative route.  It is normally performed on serum samples. But unlike the Antibody test, it could be performed on mucous swabs of the throat.  The sampling part will be identical to that used for the RNA/DNA PCR test.  It too can have secondary biochemical amplification but won’t of course have a primary analyte amplification.  It will need a very high binding strength antibody.  But even so may not be as sensitive as the RNA/DNA PCR test.  On the other hand it could be more robust for use in an airport setting! The UCL i-sense group of Professor Rachel McKendry has arguably the best example of this test under development.

On Organisational and Business:

“I completely understand the contrary stakeholder views in the airport situation. Let us take a reduction ad absurdum look at the issues:

a) The true positive and true negative rates of the best RNA/DNA PCR tests are both (95-100%).  Thus a hell of lot better than doing no tests at all! Even if quarantine was not enforced.

b) I support airport trials as soon as possible.  Cut the debate and get on with them.

c) As always when it comes to who pays, much passing the buck takes place.

d) The volume of business for the winners of the contracts will be huge. The government should seek a large discount on price/test.

e) In terms of who pays the test price – my recommendation is to add a temporary uplift on landing charges for all incoming flights.  I realise that the large and powerful airlines won’t like this. But the costs should be paid by the users I.e. passengers and airlines.

f) Lastly, the testing process and organisation must be very quick.  Passenger holding pens causing waiting times of 2-3 hours/passenger will prove unacceptable to all parties

“In summary, the technical options are clear and straightforward.  Testing should be based on risk/benefit principles prioritising protection of our nation’s health, ethical considerations and longer term economic impact over short-term buck passing on cost.  Decisions must be taken soon to avoid a serious 2nd wave.”

 

Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:

“Swab-testing at airports has limitations: testing-positive is informative (earlier quarantine of close contacts and own household) but testing negative does NOT abrogate quarantine as infection could be still incubating.

“A much more effective use of swab-testing would be within Test & Trace as has been recommended by the Royal Statistical Society ** . . .  on  a random day or pair of days during Test & Trace quarantine. Effectiveness  derives from the fact that, within Test & Trace, each external contact is known to have been in recent close contact with a symptomatic person and knows his/her last day of close contact with the index case. The external close contact’s  14-days quarantine is measured from that “last close contact” day,

“Hence, as recommended by the Royal Statistical Society**, offer swab-testing on a random-day or pair of days (eg first during days 1-5; second swab-test  during days 6-14) during quarantine to random samples of Test & Trace’s two  high-risk groups

a) households of index symptomatic cases (all members serving the full 14-day quarantine)

b) external close contacts (whose 14-day quarantine began on the day of their last close contact with index case. This could be 2 days before index case developed symptoms, hence a proportion of full 14-day quarantine will already have elapsed before this contact is asked to “stay at home”. If so, fewer than 14 days remain to be served . . . )

“By doing so, Test & Trace and we, the public, would learn about:

i) percentage testing positive prior to symptom-onset (with earlier quarantine of their close contacts as a prevention bonus),

ii) when  – during quarantine  – are close contacts are most likely to positive (which could lead to changes in quarantine-period),

iii) who – among members of the household of an index case – is most likely to test positive (and hence for whom is extra safeguarding necessary to prevent their becoming infected),

iv) whether quarantined individuals are at home on randomly-sampled days (as they should be), and

v) what proportion of the quarantine period for randomly-sampled external close contacts had already elapsed before the contact was alerted to “stay at home” (which could point to the need for further improvements in trace-efficiency of Test & Trace).

“We need answers to the above questions for persons quarantined by Test & Trace, whom we know to have been in recent contact with a symptomatic index case, before we embark on testing those returning from Spain amongst whom the swab-positive rate is likely to be lower  – as they are not known to have definitely encountered a symptomatic person while in Spain.

“Test capacity may not allow us to do both sorts of follow-up. However, random sampling can, of course, be calibrated to remain within test-capacity. But, the first priority for deployment of random sampling should be where we stand to learn most, that is: within Test & Trace.”

** Statement

https://rss.org.uk/RSS/media/File-library/Policy/RSS-COVID-19-Task-Force-Statement-on-TTI-final.pdf

and ** Devil in the Detail Appendix

https://rss.org.uk/RSS/media/File-library/Policy/RSS-COVID-19-Taskforce-Devil-in-the-Detail-Appendix-on-TTI_smb.pdf.

 

Dr Sam Clifford, Postdoctoral Fellow in Machine (Statistical) Learning and Billy Quilty, Research Assistant, Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, said:

“PCR swab tests could be an effective tool in helping stop transmission from imported cases. However, our work shows that it is best used in tandem with at least one week of quarantine. While generally having high sensitivity to detect active and symptomatic infection with COVID-19, the test’s sensitivity early on in the infection is limited, (i.e. in their latent phase), so a negative test result isn’t necessarily conclusive evidence of no infection.

“Testing immediately on arrival is likely to prevent about only 50% of infectious persons entering the community. By 7 days, a majority of people who will ever show symptoms will have noticed their symptoms and will self-isolate or seek medical attention. Also by that time, PCR testing should detect most of those infections with a long incubation period or that will never result in symptoms, so-called asymptomatic infections. We understand the need for people returning to be able to get back to their families and jobs; combining PCR with a week of quarantine could prevent up to 94% of infectious persons entering, and could help people get back a week earlier than under the current two week quarantine policy (which we estimate catches up to 99%).

“The benefits of quarantine are dependent on relative prevalence of COVID at the travel origin and destination and whether R<1 at the destination. There may be a case for relaxing the duration of quarantine from low prevalence countries provided travellers who subsequently become symptomatic self-isolate.

“Our study is available for further reading as a pre-print on medrxiv (NB: Not yet peer-reviewed): Strategies to reduce the risk of SARS-CoV-2 re-introduction from international travellers .”

 

Prof Paul Hunter, Professor in Medicine, University of East Anglia (UEA), said:

“Given that the incubation period of COVID-19 is, on average 5 to 6 days and maybe the test may becomes positive about one day before onset of symptoms and also given that the test is far from 100% sensitive even in clinically ill patients, airport screening as suggested (‘test on arrival’ and those with negative results not quarantining) will miss a substantial proportion of infected people. I am not sure how countries that do this take the sample. Is it a nasopharyngeal swab or just an anterior nasal swab? A recent study suggested that the latter easier swab to take may also be less sensitive than the NPA.

“So in my view, airport screening by PCR is not a reliable method for saying who should and who should not need to quarantine after an airport test.”

 

Prof Jose Vazquez-Boland is the Chair of Infectious Diseases at the University of Edinburgh, said:

“A “test-on-arrival” approach will help preventing the import of new infections. These tests are important to halt international transmission and to protect a country from new covid-19 flair ups after internally achieving an adequate control of the infection. As such they are an essential tool to curb the pandemic.

“If costs are a limiting factor (£150 per test has been mentioned), the PCR tests could be implemented on pooled samples. This involves assembling in a single test the swabs of a number of individuals, thus substantially reducing the demand on the testing capacity and the costs. The sensitivity of the PCR test enables implementing this approach. People would only need to isolate for a few hours on arrival until the test is performed. If a pooled sample gives a positive result, then individual tests would identify the infected subject.

“We have to be clear that the only way we have to control and eradicate covid-19 while avoiding the ill effect of indiscriminate lockdown measures is the mass, regular screening of the population for subclinical carriers, which is where the bulk of the transmission comes from.

“A systematic covid-19 testing strategy is inescapable unless an adequately protective vaccine becomes available.”

 

Dr Rob Shorten, Chair, Microbiology Professional Group, Association for Clinical Biochemistry & Laboratory Medicine:

“Testing passengers on arrival at airports would have some pros and cons.

“Firstly, there are some PCR tests that can be performed safely in this setting – these are known as ‘Point of Care Tests’, or ‘Near Patient Testing’, and can provide rapid, accurate results. However, these tend to be more expensive than laboratory-based tests and are not usually able to be performed at scale (testing an entire airplane, for example). It may be possible to take swab samples from incoming passengers and arrange for these to be tested rapidly in a laboratory. These results could then be communicated to the relevant Public Health bodies and the patient themselves to initiate isolation and contact tracing. However these tests are performed, they should be carried out to the high standards that are maintained in NHS and Public Health laboratories in the UK. Accredited, regulated Healthcare Scientists ensure high levels of quality. It is also imperative that any results are linked to NHS and Public Health data systems to ensure that subsequent public health actions can be carried out rapidly. 

“This process may detect asymptomatic and pre-symptomatic cases of COVID-19 who could transmit the infection to others. Asking these individuals to self-isolate could potentially break chains of transmission. However, it is important to understand the limitations of these tests. We know that these tests are most likely to detect the virus in the 2-3 days prior to symptoms developing and 2-3 days after. A negative test only tells us about the individuals status at that point in time. There is potential that an individual could well be incubating an infection that was not able to be detected yet.

“We must also consider that these PCR tests were developed to detect infection in unwell patients – a test for COVID-19. They are now being used to screen for COVID-19 in asymptomatic individuals. Here we must consider specificity – a measure of how certain we are that we can believe a positive result. If a test is 99% specific and we test 100 people without a disease, the test will give a negative result 99 times out of 100. The remaining one is a false positive. Even if a test has a seemingly high specificity, this is no guarantee of performance. This is particularly true when the prevalence of a disease is low. Likewise, because these tests are very sensitive, we know that we can detect the virus weeks after the symptoms of the infection has passed. It is still not clear if these positive results equate to an individual who is still capable of transmitting the infection.  

“Issuing false negative and false positive results will lead to inappropriate public health actions – people being asked to self-isolate, or being allowed to continue with their daily lives. No diagnostic test is 100% sensitive and specific, and we need to be aware of, and take into account these limitations.”

 

Prof Rowland Kao, Professor of Veterinary Epidemiology and Data Science, University of Edinburgh:

“It’s going to be important to take a cautious approach and one that is consistent across different countries. Given that, it’s also useful to remember that a ‘test on arrival’ would not have to be perfect, just reduce the risk sufficiently so that allowing people into the country from other countries w/o quarantine, or with a reduced quarantine, offers no greater risk than allowing people into the countries from locations where no test is applied.  Such an approach would of course require piloting before it was allowed – however as infections are in the process of rising across many countries, it would seem there is a good chance we have two options available. As it stands, we have to be prepared to introduce quarantine or close borders to many countries, and also be prepared for restrictions to be put in place should UK cases start rising again as could very well happen. As an alternative, government could fund a scientifically designed pilot, where individuals are tested at the airport in sufficient numbers and monitored thereafter to determine whether such an approach would work. The latter would seem to be a worthwhile investment for the future.”

 

Dr Joshua Moon, research fellow in sustainability research methods in the Science Policy Research Unit (SPRU) at the University of Sussex Business School, said:

“A test is simply a snapshot of a person’s infection status. 

“It is important to emphasise that if a person tests negative, they can test positive the next day. There is the possibility of false positive and negatives but it’s also important to note that the test works better the more virus you have in your system and early infections have low virus numbers. This is concerning as a negative test results may give people a false sense of security.

“The basic issue is that a negative test doesn’t mean you don’t have COVID-19, it just means that the test hasn’t found COVID-19. 

“That being said, testing on arrival can (if the country has the spare capacity) give you a good idea of the proportion of cases being imported, even if it is an underestimate. There are some arguments for a negative test meaning shorter quarantines (7-10 days rather than 14) but it is still risky to just let them skip quarantine altogether.

“One thing that seems to be creating issues in some places is the lack of repeat testing. This is particularly important for healthcare workers and high risk groups like retail and transport workers. Here individuals come into contact with the virus so frequently that it is important to test repeatedly to ensure that new infections and asymptomatic/pre-symptomatic individuals are caught.”

 

 

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

 

Declared interests

Prof Sheila Bird: Conflict of Interest: SMB is member of Royal Statistical Society COVID-19 Taskforce which made recommendations on remedying gaps in Test & Trace. Here is RSS press-release on remedying gaps in Test, Trace & Isolate

https://rss.org.uk/news-publication/news-publications/2020/general-news/rss-covid-19-task-force-makes-recommendations-for/

None others received.

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