The promise and the perils of antigen testing

The UK government announced yesterday that it would fund mass Covid-19 screening programmes, using fast and cheap antigen testing technology, in areas with high rates of viral transmission. This was prompted by a pilot trial in Liverpool, which the government said has “helped to significantly reduce prevalence” of the disease. 

But for a screening initiative using antigen tests to succeed, it must be carefully conducted. Antigen tests are less sensitive than molecular assays, and must be used repeatedly within a stable population if they are to keep infections under control. The cost of repeated testing mounts up quickly, and the logistical challenges, including of the subsequent contact tracing, are considerable.

Around 40% of people infected with Covid-19 are believed to be asymptomatic, but these individuals can still be infectious, so identifying and quarantining them would help enormously to curtail the pandemic.

But the Liverpool pilot met with a scathing review from Mike Gill, the former regional director of public health for southeast England, who said that for every person found truly positive, at least one other may be wrongly required to self-isolate. He warned that expanding this testing to encompass the whole country could turn out to be “an unevaluated, underdesigned and costly mess.”

Sensitivity

The UK government’s plans had already hit a different snag when it emerged that the antigen assay being used in Liverpool, from Innova Medical Group, was not intended for use as a screen – only as a means of detecting Covid-19 in patients with symptoms. None of the seven antigen tests that have been authorised by the US FDA are supposed to be used in asymptomatic people, either. 

“These are labelled for use for symptomatic patients, to confirm someone has the disease,” Eric Yager, associate professor of microbiology at Albany College of Pharmacy and Health Sciences, tells Evaluate Vantage. “And then it was thought that because of their relative cheapness and speed, they could be used off-label, asymptomatically. That wasn’t quite part of how they were tested and designed.”

A crucial point with antigen tests is that because of their relatively low sensitivity, they are of less use in communities with low rates of infection, Dr Yager says. Unlike molecular tests, antigen tests cannot be used with pooled samples. Pooled testing allows for increased throughput, and is a necessity for surveillance of large populations where prevalence of Covid-19 is low. 

Antigen tests are better suited to screening areas experiencing a surge in cases, and places where there is a high density of individuals such as schools, long-term care facilities and prisons. It is not clear exactly how high prevalence has to be before antigen testing is warranted, though Dr Yager say the threshold might be around 10%. 

Despite this, there are suggestions that antigen tests can, if deployed carefully, be used as a means of screening. In a recent article in the NEJM, Michael Mina, assistant professor of epidemiology at Harvard’s Center for Communicable Disease Dynamics, argues that lateral flow antigen tests, if used repeatedly with an individual being tested multiple times per week, could be of great help in halting the spread of Covid-19.  

Dr Mina also suggests that antigen tests be authorised for use at home since testing sites can become crowded, increasing the risk of transmission of the virus and rather defeating the point. Drive-through sites such as those currently used with PCR tests could work, but teaching people to take their own nasal samples and run the tests at home would be much safer. 

$7 per test

The appetite for antigen tests has prompted a lot of new companies to move into this space – either start-ups or groups who were not previously known for their expertise in infectious disease diagnostics. The Innova test used in the UK’s screening scheme is a case in point: it is actually manufactured by a Chinese biotech which has a partnership with Innova, and it is distributed in the UK by an obscure company called Tried and Tested, the trading name of another group called Disruptive Nanotechnology. 

Fortunately the technology on which antigen tests rely is simple: if a company can produce a monoclonal antibody that reliably binds to a viral antigen, it can make a test, Dr Yager says.

The UK government paid Innova $138.2m for its antigen tests. Assuming this covers the initial 20 million kits ordered, this works out at around $7 per test.

So far 200,000 people in Liverpool – about 40% of the city’s population – have been tested under the pilot scheme, according to the UK government. It is not clear whether these 200,000 have been tested once each or repeatedly. 

Bringing mass screening to the current high-transmission areas in the UK, which have a total population of 23 million, will require a tremendous administrative and organisational effort, particularly since the testing will have to be done outside the home. And more tests will have to be bought – many more if these communities are to be tested over and over, as Dr Mina recommends. Even at $7 per test, this is going to be expensive.