The Economist 04Apr2020

The EconomistApril 4th 2020 Science & technology 69

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should now be immune to a repeat of it. (A

negative result probably means no infec-

tion, though it could also mean that it is too

early in the course of an infection for anti-

bodies to have appeared, since the first

igms typically turn up only 7-10 days after

an infection has begun.)

Before regulators can approve a test for

widespread use, they need to validate it.

How useful it is can be summarised by two

numbers determined during this valida-

tion: its sensitivity and its specificity.

A test’s sensitivity refers to how good it

is at detecting the thing it is meant to de-

tect—in this case the igmand iggantibod-

ies associated with sars-cov-2. A sensitiv-

ity of 95% means that, from 100 blood

samples known (by other means, such as

previous genetic testing) to be infected, the

test will reliably tag 95 correctly as having

the pertinent antibodies. The remaining

five would be identified as having no anti-

bodies present—in other words they would

be false negatives.

The other significant number, a test’s

specificity, measures how good that test is

at detecting only the antibodies it is meant

to detect. There are seven human coronavi-

ruses and, ideally, a test would detect only

antibodies produced in response to sars-

cov-2. A test with 98% specificity means

that, of 100 known uninfected blood sam-

ples, 98 will come back (correctly) as nega-

tive and the final two will come back (false-

ly) as positive. Such false positives could

have many causes. A common one is cross-

reaction, in which a test responds to the

wrong antibodies.

To work out a test’s sensitivity and

specificity, it needs to be checked against

hundreds of samples of known status. Giv-

en the novelty of sars-cov-2, and therefore

the lack of easy access to relevant blood

samples, this takes time. The British and

American authorities are assessing several

tests, but have released no validation data

as yet, and have been tight-lipped about

when they will do so.

Sense and specificity

An ideal test would be 100% sensitive and

100% specific. In reality, there will always

be a trade-off between the two. Make a test

acutely sensitive, so that it gives a positive

signal with even the tiniest amounts of a

relevant antibody present, and it will get

less specific. This is because such a fine

chemical hair-trigger is likely to be set off

by antibodies similar to, but not identical

with the target. And vice versa.

This trade-off is not always a bad thing,

for it allows different sorts of test to be used

in different circumstances. For example, if

the intention of testing is to identify doc-

tors and nurses who have antibodies to

sars-cov-2, so that they can safely return

to work with infected patients, because

they are themselves now immune to infec-

tion, then the most important thing is for a

test to have a low rate of false positives. In

other words, it needs a high specificity.

By contrast, if the idea is to gather trans-

mission data, sensitivity is the priority. If

someone were identified as having had an

infection, further tests could trace which of

that person’s acquaintances were also in-

fected, or had once been infected and were

now immune. In these circumstances, a

few false positives would not be a disaster.

They would probably show up eventually,

because those around the allegedly infect-

ed individual would not be infected as of-

ten as expected. A false negative, though,

would mean lost information and a conse-

quent lack of contact-tracing. That would

be significant.

Testing of this sort will let doctors un-

derstand how a local cluster of infections

grows, and therefore what action to take in

order to break the chain (meaning, in prac-

tice, who needs to be quarantined). This

kind of contact-tracing and isolation has

been employed to great effect in South Ko-

rea through the use of genetic tests for the

virus. Antibody tests will enhance the pro-

cess, by capturing data on those infected in

the past as well as the present.

Children are another group who could

profitably be monitored using antibody

tests. It is now well established that they

T

he seven Formula 1 teams in Britain

have high-tech engineering centres

stuffed with the latest production equip-

ment. And they employ hundreds of staff

with the talent to use this gear to design,

test and manufacture parts rapidly, in the

days between races. With the season

suspended, they have been collaborating

on ways to help produce ventilators,

which are needed urgently to treat pa-

tients suffering from covid-19. This week

one team, Mercedes-amg, obtained

approval for a device which it can quickly

manufacture by the thousand.

The machine is not a ventilator, but a

breathing aid of a type known as a con-

tinuous-positive-airway-pressure (cpap)

device. These are typically used to assist

people who have breathing problems to

sleep more soundly. The machine deliv-

ers air at slightly above atmospheric

pressure via a mask placed over the nose

and mouth. This helps keep open the

alveoli of the lungs. (These are the sacs

from which blood absorbs oxygen, and

into which it dumps carbon dioxide.)

That reduces the effort of breathing.

Additional oxygen can also be added.

According to reports from Italy, around

half of patients given cpaptreatment

have avoided the need for invasive me-

chanical ventilation, in which a tube is

inserted down a patient’s throat.

Mercedes-amgworked with a team at

University College, London, to take apart,

copy and improve an off-patent cpap

machine in a matter of days. As it was

based on an existing design the British

government’s medical regulator was able

to fast-track approval. The team also

worked with Oxford Optronix, a small

British firm that makes oxygen monitors.

The first 100 devices have now been

delivered to University College Hospital

and other London hospitals for clinical

trials. These are expected to take three or

four days. If they are successful, the team

reckons it can make 1,000 of the cpap

machines a day at its base near North-

ampton, and distribute them thence to

other hospitals around the country.

“The speed with which the team

developed the device is remarkable,”

reckons Duncan Young, a professor of

intensive-care medicine at Oxford Uni-

versity, who is not part of the project.

Patients too unwell for simple oxygen

masks, but not ill enough to need a venti-

lator, can be treated with a cpapmach-

ine, says Dr Young. This could, he adds,

save lives by freeing up ventilators for

those in urgent need of them.

A racing chance

Treating patients

Formula 1 comes up with a breathing machine

Quick-change artists