Wednesday, 1 April 2020

Covid-19: what tests do we need?

My previous post summarised (*) the currently-used test for Covid-19, the PCR test, including its various limitations.

So what would improve it? Any new test would have to be:

*) Accurate. This means it would have as few false negatives and false positives as possible. Greater than 85% accuracy would be good. Chasing higher values (e.g. >95%) might delay the availability of tests, and allow the best to be the enemy of the good.

*) Sensitive. Sensitivity is the percentage of people with the disease that test positive. A patient may only have low amounts of virus in their system, especially early on, and therefore a test needs to be able to detect these low levels.

*) Selective. Selectivity is how well the test can separate the target disease (in this case Covid-19) from other, similar diseases.

*) Timely. Ideally, a patient or doctor would take a swab, and the result would come immediately, as it does with a pregnancy test or breathalyser. Any positives could then be taken through the existing PCR process for validation. Ideally, it would err towards false positives over false negatives.

*) Portable. Ideally it would be portable; the test can be conducted in hospitals, doctor's surgeries, or even in the home.

Various companies claim to be near this holy grail, and I hope they are correct. Ideally it would be multiple companies, allowing countries and organisations to choose which test - or tests - they believe are the best. South Korea have a rapid test that appears to be based on a speedier PCR process, but details on it appear to be sparse. However any PCR-based test will, by its very nature, be complex to administer.

Serological tests

Whilst PCR-style tests are useful, we also need other tests. The current PCR test only indicates if you have the disease; if you have had it, been symptomatic and beaten it, it will show up as a negative. Therefore we also need a serological test as well. This would show whether an individual has developed antibodies against this virus. Such a test could give us information on how prevalent Covid-19 has become in the community.

Serological tests are being developed by various groups. It appears that most will require a pinprick sample of blood, and the tests will be able to be performed in larger batches than PCR tests, easing restraints on laboratories. However the tests only work seven to fourteen days after the onset of symptoms, so there is still a need for PCR tests.

Many of the requirements for a PCR test are also required for a serological test: it will need to be sensitive, selective and timely.

For this reason, care needs taking that any newly-developed tests are actually fit for purpose, particularly in relation to false positives (in the case of antibody tests, false positives are more dangerous than false negatives. This is the opposite to PCR tests, where false negatives are the bigger problem).

There are other tests that might be useful, but the big two are the 'have-you-got-it-now' and the 'have-you-had-it' tests. Once we have these available in massive volumes, then we can start planning how to get back to normality. Without them, normality is a much rockier road.

Beware, the hustlers

Vast amounts of money will be available to anyone who manages to make a 'Holy Grail' test, and this will attract not only genuine actors, but charlatans. Some of these will be unknowing charlatans - people who genuinely believe 'their' solution is the Holy Grail when it isn't, whilst there will be genuine charlatans - snake-oil salesmen looking to make a quick buck. They will get discovered, but they could do massive damage in the meantime.

And before anyone thinks this doesn't happen, just remember James McCormick and the hideous ADE bomb-sniffer scandal (2). If people want something badly enough, others will sell them it - even if the item sold is worthless.

In addition, newly-developed tests would usually be run through trials to try to gauge accuracy, sensitivity and other values. The understandable hurry to get new tests out and used may lead to less understanding of the test itself, its limitations, and how it is to be administered.

A happier thought

It feels somewhat wrong - frivolous, perhaps - to say so, but this hideous disease has struck us at the best time in our history. We are not prepared, but we have the science and technology to fight it. We have a few decades of experience with genetic assaying as an invaluable tool in the battle, and we have had a few near misses in which we have developed basic tools. It can - and will be - argued that we should have done more after those near misses, but we're closer to winning the battle then we were.

Then there is another aspect: the Internet. Fifty years ago, the idea of essentially quarantining the entire country would have been unthinkable, from both an economic and social point of view. Now, the Internet allows us to communicate, order food, and in many cases even work from home. The Internet provides us with an invaluable tool in the battle - both economic and social.

(*) hopefully with a modicum of accuracy.


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