CORONAVIRUS

Isolate fast and curtail infection: how antigen tests are changing the face of the pandemic

The diagnostic tool has become key to curbing transmission in the second wave as it quickly identifies positive cases, meaning they are isolated immediately and do not spread the virus

A person infected with Covid-19 goes through a four-to-five day incubation period before becoming infectious.

This person can infect others for around eight days. After that, the viral load is low and the disease is no longer transmitted.

Let’s imagine that this person has eight close contacts and infects four of them if nothing is done to prevent it.

Every infected contact will go through their own incubation period followed by an infectious cycle when transmission is possible.

What happens if this person sees a doctor and gets a PCR test? He or she will be told to self-isolate preventively, but it will be two or three days before they know they have tested positive.

There are people who do not strictly observe the preventive isolation, and they may infect others during that time. That is how Contact 1 gets infected.

If the first person’s contacts are traced following the positive result, all eight may be located and isolated. But there will still be quite a few opportunities for passing the virus to others.

What if we perform an antigen test? Within 15 minutes of going to the doctor’s, the person will get the positive result back; self-isolation and contact tracing can begin immediately.

The speed of antigen tests prevents new opportunities for infection.

Antigen testing is changing the war against Covid-19. In Europe and the US, it is an increasingly popular strategy, now accounting for 30% of all testing in Spain when it was barely part of the equation until September. The tests are associated with screening, but they are already the preliminary test for patients with symptoms in hospitals and primary care centers. The European Commission also recommends their use in care homes and other places where outbreaks occur, as well as to track close contacts.

These tests have two big advantages: they are fast and they are cheap. They detect the antigen proteins that allow positive cases to be identified. A swab is taken from the patient’s nose with results available in less than half an hour. The main difference from a PCR test is that the sample does not have to be sent to a laboratory to obtain the result. In the following graph we can see the evolution of the viral load and the duration of the infectious phase, when detecting positive cases is vital.

Infectivity

Infection

S

Day 1

Day 6

Day 12

1

One person with Covid-19 can infect others over a period of several days. Before that, there is an incubation period; afterward the viral load becomes low and there is no more transmission.

Viral load

Infectivity

S

Day 6

Day 12

Onset of

symptoms

Result

in several

days

PCR

Result

in 15 minutes

Antigen test

2

During the infectious phase, the viral load is high and both the PCR and the antigen test will detect the virus. The advantage of the antigen test is that in 15 minutes we know if we are positive. This makes it possible to isolate the positive person and their contacts faster.

Infection

Infectivity

S

Day 1

Day 6

Day 12

1

One person with Covid-19 can infect others over a period of several days. Before that, there is an incubation period; afterward the viral load becomes low and there is no more transmission.

Viral load

Infectivity

S

Day 6

Day 12

Onset of

symptoms

Result in

several days

PCR

Result

in 15 minutes

Antigen test

2

During the infectious phase, the viral load is high and both the PCR and the antigen test will detect the virus. The advantage of the antigen test is that in 15 minutes we know if we are positive. This makes it possible to isolate the positive person and their contacts faster.

1

One person with Covid-19 can infect others over a period of several days. Before that, there is an incubation period; afterward the viral load becomes low and there is no more transmission.

Viral load

Incubation

Infectivity

Infection

S

Day 1

Day 6

Day 12

Onset of

symptoms

Result in several days

PCR

Result

in 15 minutes

Antigen test

2

During the infectious phase, the viral load is high and both the PCR and the antigen test will detect the virus. The advantage of the antigen test is that in 15 minutes we know if we are positive. This makes it possible to isolate the positive person and their contacts faster.

1

One person with Covid-19 can infect others over a period of several days. Before that, there is an incubation period; afterward the viral load becomes low and there is no more transmission.

Viral load

Incubation

Infectivity

Infection

S

Day 1

Day 6

Day 12

Onset of symptoms

Result in several days

PCR

Result

in 15 minutes

Antigen test

2

3

During the infectious phase, the viral load is high and both the PCR and the antigen test will detect the virus.

The advantage of the antigen test is that in 15 minutes we know if we are positive. This makes it possible to isolate the positive person and their contacts faster.

It’s fast, but is it sensitive?

“The biggest advantage of the antigen test is that it’s fast,” says Stephen Kissler, an infectious disease researcher at Harvard University. “In a community transmission scenario, what we want to know is if a patient is contagious. The antigen test is the most powerful tool we have to establish that.” Until a few months ago there were some doubts about its sensitivity: how many positive cases could escape an antigen test compared to a PCR?

Recent studies indicate that antigen tests are, in fact, quite sensitive, especially when it comes to detecting people during the contagious phase of the disease. We know that 20% of the PCR tests showing up positive turn up negative in antigen tests: in other words, they are false negatives and usually involve patients with a low viral load who will scarcely transmit the disease. According to a recent study in Spain, “patients who are PCR-positive but test negative with a rapid test are probably not contagious.”

Other preliminary research puts the sensitivity of rapid testing at above 93% when the viral load is high, even in asymptomatic cases. So the antigen tests would perform particularly well in cases “associated with a high risk of transmission.”

PCR and antigen tests are sensitive and they can detect the virus during the infectious period, when the viral load is high.

Infectivity

S

Day 6

Day 12

Possible detection

with PCR

Possible detection

with antigen test

Antigen tests become less sensitive when the viral load is low and the patient is no longer infectious.

PCR and antigen tests are sensitive and they can detect the virus during the infectious period, when the viral load is high.

Infectivity

S

Day 6

Day 12

Possible detection with PCR

Possible detection

with antigen test

Antigen tests become less sensitive when the viral load is low and the patient is no longer infectious.

PCR and antigen tests are sensitive and they can detect the virus during the infectious period, when the viral load is high.

Viral load

Infectivity

S

Day 1

Day 6

Day 12

Possible detection with PCR

Possible detection with antigen test

Antigen tests become less sensitive when the viral load is low and the patient is no longer infectious.

PCR and antigen tests are sensitive and they can detect the virus during the infectious period, when the viral load is high.

Viral load

Infectivity

S

Day 1

Day 6

Day 12

Possible detection with PCR

Possible detection with antigen test

Antigen tests become less sensitive when the viral load is low and the patient is no longer infectious.

It seems that most of the positive PCR-tested cases that go undetected by the antigen tests are people who have had the infection but have mere traces of the virus in their systems. Detecting these cases is relevant if we want to know if someone has had the virus, but not when it comes to breaking the chain of infection. “We can do without that level of sensitivity to gain ground in areas that have proved problematic, such as the time it takes to identify positive cases and isolate them,” says Sonia Zuñiga, a researcher with the Spanish National Research Council (CSIC). “Now the person is isolated much sooner and more chains of infections are broken.”

How can the rapid tests help to curtail infection? Below are three examples.

The first advantage of the rapid test: early quarantine

Waiting for a PCR test result has been a daily occurrence for months. Someone would go to the doctor with symptoms, be tested and sent home to self-isolate until they found out they were positive days later. The advantage of antigen testing is obvious: you will leave the doctor’s office knowing the result. If you test positive, there will be less pressure to continue going to work, taking the kids to school or helping an older relative. You won’t be tempted to carry on with normal life, saying to yourself, “It’s probably the flu.”

Isolation after positive test

S

With a PCR test it will take several days to know if you are infected, and you will be told to self-isolate preventively until the results are available.

Isolation after positive test

S

With an antigen test, you go home knowing that you have the virus.

Isolation after positive test

S

With a PCR test it will take several days to know if you are infected, and you will be told to self-isolate preventively until the results are available.

Isolation after positive test

S

With an antigen test, you go home knowing that you have the virus.

With a PCR test it will take several days to know if you are infected, and you will be told to self-isolate preventively until the results are available.

Isolation after positive test

S

With an antigen test, you go home knowing that you have the virus.

Isolation after positive test

S

Un aislamiento más estricto puede

evitar nuevos contagios

With a PCR test it will take several days to know if you are infected, and you will be told to self-isolate preventively until the results are available.

Isolation after positive test

S

With an antigen test, you go home knowing that you have the virus.

Isolation after positive test

S

Stricter isolation can prevent new infections

The speed of the diagnosis can improve quarantine compliance, which is no mean feat: two recent surveys in the UK indicate that many people with Covid-19 symptoms do not self-isolate of their own accord.

It also helps in hospitals. “You have to make quick decisions in the emergency unit,” says José Ramón Arribas, a doctor at La Paz hospital in Madrid. “It’s essential to have an instant result when deciding whether to send a patient with symptoms home (where they would be advised to take the necessary measures) or whether to admit them. Besides, doing an antigen test allows for the human and material resources needed for a PCR to be made available.”

Faster tracing

Testing people suspected of carrying the virus, tracing their contacts and asking them to isolate themselves has been the mantra during the pandemic. But it demands a blistering speed that appears to be achievable only in countries like South Korea. As the epidemiologist Adam Kucharski puts it, “SARS-CoV-2 can be transmitted before the onset of symptoms, so by the time a symptomatic case is detected, they may have infected others, which means that conventional testing and tracing is always playing catch-up.”

Antigen testing speeds up the process. When a person goes to the doctor with symptoms, the antigen test will indicate instantly if they are infected and contact tracing can begin immediately, without having to wait days for the result. This means a head start of two to three days with regard to locating contacts, asking them to self-isolate and monitoring their symptoms. “My impression is that this has been a turning point,” says Juan Torres Macho, a doctor at the Hospital Infanta Leonor in the Madrid district of Vallecas, “because it makes it possible to break chains of infection more quickly and locate contacts more quickly. In the past, PCR tests could take three to six days.”

PCR

Antigen test

S

S

PCR

Antigen test

S

S

PCR

Antigen test

S

S

PCR

Antigen test

S

S

On the recommendation of numerous international agencies, the antigen tests have been used in symptomatic cases – an area that has been more thoroughly researched by manufacturers. But some studies suggest they may also be used for close contacts that are asymptomatic. In fact, the European Commission recommends their use both with asymptomatic close contacts and also in outbreak scenarios. If their sensitivity is found to be sufficient, the faster, more convenient and cheaper antigen tests would allow dozens of tests to be done on people who have been in contact with a positive case.

New possibilities: mass testing

In a number of countries, including Spain, India and the UK, mass screening has been done to detect positive cases in specific locations such a university campus or a neighborhood. If thousands of people are tested, positive cases can be located. But the strategy comes with certain challenges.

The first is false positives. Some of the people who test positive in a screening will not actually be infected. The numbers giving a false result range from between 10 to 150 per 10,000 tested, depending on the specificity of the antigen test. For example, in Slovakia, two-thirds of the population has been tested and the 57,000 who tested positive have been quarantined, despite the fact that some will not have the virus.

The second problem is that a screening is always a snapshot of an evolving situation. “Both the PCR and antigen tests only indicate the incidence of the virus at a given moment,” explains Zuñiga, from CSIC. If it’s the only snapshot taken, there is a risk of overlooking infected people in the incubation period. According to a number of experts, the solution is to test frequently, a scenario in which the antigen tests again have the upper hand.

It is not clear whether the screening done so far has worked particularly well, but it is possible that the effectiveness of antigen tests in mass testing scenarios will improve in the coming months. There is even talk of individual tests – something akin to the kind of home testing done to establish pregnancy. “Once we have cheap, fast and self-executable antigen tests, they may become mandatory for risky activities such as traveling by plane, dining in a restaurant or getting together with a group of friends for a few days,” says Carlos Velayos, an intensive care doctor at Fuenlabrada hospital in the Madrid region. Even when the vaccine arrives, the virus will not completely disappear and it will still be important to protect ourselves as best we can.

English version by Heather Galloway.

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