Different paths to the same destination: screening for Covid-19

At present, polymerise chain reaction and antibody testing are the dominant ways that global healthcare systems are testing citizens for Covid-19. Both techniques have their caveats, and as the crisis unfolds researchers are looking into alternative ways to screen for the deadly disease. Chloe Kent looks into the science behind existing tests, and what alternatives are starting to present themselves.


ver the course of the current Covid-19 crisis, the importance of reliable, accessible testing to screen for the disease has become increasingly apparent. South Korea, where tests for the disease were made promptly and readily available when the outbreak first hit, has had a drastically lower death rate than counties which have responded less promptly. Only 244 Covid-19 fatalities have been recorded in South Korea out of 10,752 recorded cases, compared to the UK, which has seen 21,092 deaths out of 157,000 confirmed cases.

The Wall Street Journal has reported that South Korea can test more than 20,000 people every day at 633 testing sites nationwide. The test sites - many of them drive-through - have been free to use, and results are provided by text within 24 hours.

The majority of tests for Covid-19 can be divided into polymerise chain reaction (PCR) or serologic tests. Both of these tests use different kinds of samples to search for different hallmarks of the SARS-CoV-2 virus – and neither of them are exactly perfect.

What is PCR testing?

“At the moment the majority of the current Covid-19 tests that all the reports are coming from are using PCR,” says University of Sussex senior lecturer in microbiology Dr Edward Wright. “They detect the genetic information of the virus, the RNA. That’s only possible if the virus is there and someone is actively infected.”

PCR tests are used to directly detect the presence of an antigen, rather than the presence of the body’s immune response, or antibodies. By detecting viral RNA, which will be present in the body before antibodies form or symptoms of the disease are present, the tests can tell whether or not someone has the virus very early on.

“False negatives can occur up to 30% of the time with different PCR tests.”

“PCR gives us a good indication of who is infected. They can be isolated and get in contact with people they’ve been in touch with so they can be quarantined too, just in case. That’s the true advantage of the current major diagnostic tests, you can break that transmission chain and get a clearer picture of what’s happening,” says Wright.

By scaling PCR testing to screen vast swathes of nasopharyngeal swab samples from within a population, public health officials can get a clearer picture of the spread of a disease like Covid-19 within a population.

It’s worth noting that PCR tests can be very labour intensive, with several stages at which errors may occur between sampling and analysis. False negatives can occur up to 30% of the time with different PCR tests, meaning they’re more useful for confirming the presence of an infection than giving a patient the all-clear.

Warwick Medical School honorary clinical lecturer Dr James Gill said: “During the course of the outbreak, the PCR testing has been refined from the initial testing procedures and with the addition of greater automation to reduce errors. As such, we now have an 80%-85% specificity – i.e. the chance the test is detecting the virus.

“Remember as we are looking at swabs taken from people, who have lots of other organisms floating around, we are essentially dealing with the question of how ‘right’ the result we are looking at is.”

What is serologic testing?

Wright says: “An antibody test tells us what proportion of the population has been infected. It won’t tell you who is infected, because the antibodies are generated after a week or two, after which time the virus should have been cleared from the system. But it tells you who’s been infected and who should be immune to the virus.”

It’s not yet clear how long any immunity period after a Covid-19 infection will turn out to be. Historical studies have indicated that people who survived the 2003 sudden acute respiratory syndrome (SARS) outbreak had antibodies in their blood for years after recovery. Both SARS and Covid-19 are caused by coronaviruses, but it’s too early to say if Covid-19 will generate a similar immune response. Reports also indicate that some people have been infected with the virus twice over, meaning these particular patients didn’t develop any immunity at all.

“An antibody test tells us what proportion of the population has been infected.”

All that said, if public health officials can get a handle on what proportion of the population are theoretically immune to the virus, the information could help lift the social distancing restrictions on movement.

“If there’s a high enough level of people in the population who have immunity, they will then stop this virus from circulating within the population, which is known as herd immunity,” says Wright. “If someone is infected, as long as the people around them have immunity the virus won’t be able to spread.”

Unlike PCR tests, which commonly use swabs to detect Covid-19, blood samples are usually used for antibody tests. This is because there will be a very small amount of the coronavirus circulating in the blood compared to the respiratory tract, but a significant and measurable antibody presence.

How about a lateral flow assay?

Canadian firm Sona Nanotech has been attempting to push a completely different kind of rapid screening test for Covid-19 to market. It’s a quick-response lateral flow assay, and the firm says it expects its test to produce results in five to 15 minutes, cost less than $50 and be administrable by untrained individuals.

Lateral flow assays have a wide array of applications and can test a variety of samples like urine, blood, saliva, sweat, serum, and other fluids.

All lateral flow tests are designed to identify the presence of a specific biological marker. Pregnancy tests, for example, look for the hormone hCG produced by pregnant people while HIV lateral flow assays detect the virus directly.

“All lateral flow tests are designed to identify the presence of a specific biological marker.”

Sona owns a proprietary gold nanorod technology which can be used in numerous lateral flow applications. In lateral flow tests, particles like Sona’s nanorods are used to bind to biological materials and carry them along a test strip, producing a positive or negative result.

This isn’t a PCR test which requires a swab, a wait and specialist analysis to yield a result. Many antibody tests rely on lateral flow, but it isn’t one of those either, as Sona’s test will directly detect the Covid-19 virus.

The ease-of-use of Sona’s technology should make it suitable for in-home testing and monitoring, to help identify if patients need treatment in a clinical facility. It should also be able to verify if people are ready for release from quarantine and to screen individuals prior to entering closed public venues like aeroplanes. As of April, the company has been accepting pre-orders.

Rapid in-clinic antigen testing

Bosch has also taken an innovative approach to Covid-19, developing a point of care swab test designed to produce results in under two and a half hours.

Running on Bosch’s pre-existing Vivalytic analysis device, the company says the test is one of the world’s first fully automated molecular diagnostic tests that can be used directly by all medical institutions.

“The Covid-19 quick test from Bosch is one of the world’s first fully automated molecular diagnostic tests.”

Vivalytic consists of an analyser device and matching test cartridges. There are biological components in each of the cartridges that are used to prove whether a sample contains SARS-CoV-2 or nine other respiratory viruses. This eliminates the need for further tests if a patient doesn’t have Covid-19, but is presenting with one of the nine other infections.

The test has been available in Germany since April, with other European markets to follow.

A Bosch spokesperson says: “The Covid-19 quick test from Bosch is one of the world’s first fully automated molecular diagnostic tests that is able to determine an infection with SARS-CoV-2 and nine other respiratory viruses within 2.5 hours. It is therefore an antigen test.”

The more testing, the clearer the picture

If quick-response antigen tests like the ones from Sona and Bosch are effectively deployed across the worldwide healthcare ecosystem, they could play a crucial role in stopping the spread of Covid-19.

Antibody tests will still be vital in determining any immunity that develops among the population, but these antigen tests can be used to confirm cases of active SARS-CoV-2 infection without PCR’s arduous process of laboratory testing. While Bosch’s Vivalytic system isn’t designed to leave healthcare settings, Sona’s is suitable for home use. What counts now is that these tests and others like them are actually able to make their way to the patients that need them.

“It’s vital that testing, whether it’s PCR or antibodies, is ramped up.”

“The more testing you do the clearer the picture is on who is infected and thus who needs to be isolated,” says Wright.

“Singapore, South Korea, Germany, they seem to have had a better course of the pandemic so far than other countries who don’t have such a high testing capability. That can help alleviate some of the restrictions on movement sooner and give a better idea of what’s going on. It’s vital that testing, whether it’s PCR or antibodies, is ramped up as much as possible to provide clear evidence on what is happening and where we should be going.”