Thursday, 2 April 2020

Who should we test for Covid-19?

In an ideal world (or country...) we would be testing everyone for Covid-19 at regular intervals. We would get a pack by post, we would do a swab or pinprick test, and get an immediate result, like a pregnancy test or breathalyser. Then, if it is a positive result, you have another, official test done and isolate yourself and others in your household.

There would be many problems with this: people may not bother to do the tests; they may not perform them correctly or frequently enough, or they may just fake the results, especially if there is a compelling reason for them to do so (e.g. being allowed to go out of the house). However, such a routine should produce enough data to massively restrict the spread of the virus (a reproduction rate of less than one, where each ill person infects less than one other person) and keep the economy and country going.

There is one problem: the technology to do this does not exist, and the technology we do have is much more complex to administer. I covered this previously.

It is not just a case of producing / obtaining enough kits at a time when virtually every country in the world is screaming out for them (and in some cases, like in Spain, obtaining worthless ones (1)). The current test requires a swab to be taken, the swab to be sent to a lab, and a complex polymerase chain reaction (PCR) test performed on it (2).

This all means we do not have the ability to perform enough tests, and we have to ration them. This is where critical choices need to be made. We do not have enough tests to do everyone, so who do we choose?

Patients
An obvious one is patients. Sadly, the telltale symptoms of Covid-19 are coughing and an elevated temperature, which can all be symptoms of common-or-garden influenza or other illnesses. If someone has bacterial pneumonia, they need treating with antibiotics, and not the same treatment as Covid-19 patients - even if the symptoms appear the same. Knowing who has Covid-19 allows doctors to prioritise and tune their treatment, which is vital with a disease that sadly seems to linger in the critically ill: even when a patient is in intensive care, the road back to health is long and arduous. But this symptoms of this illness are not specific enough, and there are too many people who are potentially symptomatic for them all to be tested: we are already having a very high negative rate (i.e. testing people who turn out not to have it).

NHS Staff and other frontline workers
Another obvious one is any front-line NHS staff who are symptomatic. Currently, doctors and nurses exhibiting symptoms are having to self-isolate for at least a week. If they are clear of Covid-19, then they could be helping patients. However what if testing a nurse means a patient remains untested, and gets incorrect treatment as a result? What if asymptomatic doctors continue to spread the illness? Do you test all of the nearly million-strong NHS frontline staff?

There are other issues. *If* the false negatives are too high, then it would cause front-line NHS workers to go back to work whilst infectious, and infect other people - especially other front-line workers. If the false negative values is that high, then it would be safer to keep any such worker who shows symptoms away from patients, the vulnerable and fellow key workers. This would depend on the false negative values of the tests - and that is generally somewhat of an unknown at the moment, and small value changes could have large consequences. A way around this is to perform two separate tests on such key workers, with two separately-taken swabs sent to two different labs. But even this does not mean perfection with a low enough false-negative value, and uses up more of the required tests.

Contacts
Yet another is to test contacts of people who have already tested positive, to inform and influence personal behaviour and national policy. This 'contact tracing' is said to have worked well in South Korea.

High-risk groups
Another priority might be people in very high-risk groups: for instance care homes and prisons, where an infection could rapidly spread through a closely-congregated population.

Other uses
There are other requirements to add into this: for instance, it might be very useful from a data point of view to do a randomised sampling to see how many people have currently got Covid-19, but are asymptomatic (the current tests do not highlight if you have had it and have recovered; for that we are awaiting a reliable antibody test or similar). This data might be very useful in modelling the spread of the disease, but would use up many kits we do not have. A study in the small Italian village of Vò performed in early March indicated that many people are infected but asymptomatic. (4) The asymptomatic people can still spread the disease, even if they are perfectly healthy.

Also, a certain number of the kits should be tested (preferably randomised samples of batches) to ensure that each batch of kits is performing correctly. Laboratory technicians also need to be tested as part of the process, to ensure they are performing the tests correctly. Confirmatory samples should perhaps be sent between labs, to validate their work. Such tests may require small numbers of kits, but the small numbers add up.

And hence the problem
There are not enough kits for even a small part of all this. And so we get into a classic situation of a constrained critical resource.

To make matters worse, it's perfectly possible that the hurried tests that are being done are so inaccurate that they are essentially pointless: the higher the proportion of false negatives there are, the more worthless (and indeed dangerous) the test. I don't feel that's the case, but it's possible.

So who to test? I don't know, and I fear there is no clear or easy answer: and worse, the answer may change as we gain knowledge of this disease, and both our ability to test and test accuracy increase.

The good answer, obviously, is to massively increase the number of tests that can be performed: although that is much easier said than done with the existing PCR test, and has massive logisitical and practical issues.

Therefore we await newer, faster tests - especially ones that do not require a lab to analyse them.

But until such tests are widely available, I'm glad I'm not the one trying to make policy on this.

In other news:

One of the problem with this story is that it moves rapidly. Since the last couple of posts, I have come across new stories and angles.

There is hope for such tests, for instance from the US (5) and here in Cambridge (6), amongst others. As an aside, an interesting thing about the UK-made Samba-II machines is their price: £2.4 million for 100 machines means each costs £24,000 - incredibly cheap. I can only hope that the consumables such as reagents are easily available.

(1): hhttps://www.voanews.com/science-health/coronavirus-outbreak/chinese-firm-offers-replace-faulty-test-kits-sold-spain
(2): https://www.medicalnewstoday.com/articles/coronavirus-testing#how-does-it-work
(3): https://www.fda.gov/media/136151/download
(4): https://www.bmj.com/content/368/bmj.m1165
(5): https://www.vox.com/science-and-health/2020/3/28/21198021/coronavirus-test-abbott-fda-covid-19-5-minutes
(6): https://www.cam.ac.uk/research/news/rapid-covid-19-diagnostic-test-developed-by-cambridge-team-to-be-deployed-in-hospitals