A guide to COVID-19 Testing Methods
By Anna Paternnosto & Ophélie Guillouet-Lamy
As the Covid-19 pandemic is spreading across the globe, the economic and social consequences of the crisis are becoming more critical. And subsequently, the necessity for governments to be able to quickly test their population to the virus is a time sensitive issue. Indeed, the sooner states will be able to test efficiently and massively their population, the sooner individuals and companies will start living and operating normally again, and the sooner the situation will come back to an ante-Covid-19-state. But for that to happened, states must first define their Covid-19 Testing strategies, based on the existing testing research and technologies available. At this time, three main methods exist for the testing of Covid-19 virus. These three methods differ from one another by the way the sample collection for testing is done, the element they detect, the rapidity and their detection rate capacity. First, we will review the RT-PCR Test, which detects the presence of the virus itself, and can only be done in a laboratory setting. Second, we will present the two types of Rapid Diagnostic Tests which do not require the supervision of a laboratory or medical staff: the Antigen detection Test is meant to detect the presence of a protein which is present in the virus while the Antibody detection Test is detecting the antibodies produced in response to the infection by the virus.
Let’s start with the RT-PCR Test, which stands for ‘reverse transcription polymerase chain reaction Test’, which detects the presence of the virus itself. This test is done by using respiratory samples (sputum or nasopharyngeal swab) and is achieved by monitoring the reaction using fluorescence. The test locates a coronavirus gene sequence and creates multiple copies that can then be easily detected. These tests with throat swabs detect the genetic information of the virus, which is only possible if someone is actively infected. Therefore, they are only reliable in the early stages of the disease: after a week the virus can disappear from the throat and multiply in the lungs. Infected people in their second week would then need to be tested by taking samples of the deep airways (suction catheter or coughing up material). The test can be useful from a few days after infection (even pre-symptomatic) to a couple of weeks after the first symptoms (and even longer for individuals which are acutely ill). The results are generally available within few hours to 2 days. They are very effective, but their effectiveness depends on how well the swab is taken: if the virus is not picked up by the swab, the test will be negative. In fact, false negatives can occur up to 30% of the times. Hence, the test is more useful for confirming the presence of the infection rather than giving the all clear. It allows to identify and isolate infected people and can therefore help to break the transmission chain.
The Antibody Test, or also referred to as Serology Test, shows the presence of antibodies generated in response to the Covid-19 virus via blood samples. Thus, it helps to identify those who have already been infected and who should now be immune from reinfection, but it does not indicate if a person is infectious or not. So, for instance, by putting a sample of the virus directly on the test, the test result would be negative, since no antibodies would then be detected. Furthermore, antibody tests should only be done starting from one week after symptoms disappear because it takes time for the antibodies to be created. Now let’s get a bit more specific regarding the antibodies. After being infected by the Coronavirus, an individual can present different types of antibodies. We will here focus on two types of antibodies present in a Coronavirus infected individual: IgM antibodies (Immunoglobulin M) are present early in the infection, whereas IgG antibodies (Immunoglobulin G) arise a few days later. IgM are the first response to an infection (5-10 days from infection): they are the “fast reaction force” of the human body. On the contrary, IgG shows that someone has had the virus and is now protected from the virus. These IgG can be detected in a patient’s blood usually within 14 days after the infection: they represent the slower, but more “powerful army” of the human body. If someone’s test is positive to both IgG and IgM, this suggests that the person might be within the first month of infection. In case of re-exposure, a large number of “soldiers” from the “powerful army” (IgG) will be deployed within 24 to 48 hours and will hopefully prevent new infection. Many tests can distinguish between IgM and IgG and thus give information on the phase of infection (early/current vs later stage/previous infection).
Source: DIAZYME Laboratories Inc.1
However, despite the accuracy of these tests, one should not rely completely on it to assert someone’s immunity, since reports indicate that some people have been infected twice, which means they did not develop any immunity. Furthermore, it has been proved that less severe seasonal coronaviruses circulating in the community can induce antibodies that cross-react in a Covid-19 antibody test to produce false-positive results. Nevertheless, some countries like Sweden or The Netherlands have already bet on the strategy of ‘Herd immunity’, which endorses the idea that a high percentage of the population will most certainly get the virus, but that a higher level of immune people will stop the virus from circulating. And on the eve of the deconfinement, a growing number of countries will certainly start considering this strategy as well. Serology testing is in this case proving its relevance, as it is generally used in epidemics to aid in the investigation and surveillance of the outbreak, in order to better understand the rate and pattern of the infection. Based on current data (8 April 2020), WHO does not recommend the use of antibody-detecting rapid diagnostic tests for patient care but encourages the continuation of work to establish their usefulness in disease surveillance and epidemiologic research.
One of the other main testing methods available at this moment is the Antigen test, which detects the presence of a protein of the virus in secretions of the upper respiratory tract. Antigen tests detect the viral components present during the infection, and therefore are relevant at the acute or early stage of infection. Like the antibody tests, they are Rapid Diagnostic Tests, which means the results are available within few minutes and they do not require a laboratory setting. How does it work concretely? The target antigen, if present in sufficient concentration in the sample, will bind to specific antibodies fixed to a paper strip. However, here again, the result of the test depends a lot on how well the swab is taken. False positive results could occur if the antibodies on the test strip also recognize antigens of viruses other than Covid-19 such as the coronaviruses that cause the common cold. These tests are currently not recommended for clinical diagnosis pending more evidence on test performance and operational utility. With the limited data now available (8 April 2020), WHO does not currently recommend the use of antigen-detecting rapid diagnostic tests for patient care, although research into their performance and potential diagnostic utility is highly encouraged.
What conclusions can we draw?
In many countries there is a shortage of PCR machines and reagents. In addition, getting the results of PCR takes time because a laboratyory setting with trained personnel is required. As a result, new Rapid Diagnostic Tests have been developed (Antigen test and Antibody test). The political and scientific communities still debate on how to make best use of these methods. For now, researches show that the most effective way to detect an early infection would be to combine the antibody test and the PCR test, which can give a 98.6% detection rate in the first 5.5 days. The Table below (Source: DIAZYME Laboratories Inc2) gives an accurate synthesis of the different infection scenarios that can be encountered while combining the different tests and their results.
Some elements still remain unclear and prevent the scientific community from drawing clear conclusions and making decisive recommendations. For instance, it is still unclear how long one’s immunity can last. Also, the impact of releasing false positive individuals (Antibody test) could be very high and is to be considered. Finally, we still don’t know if the Covid-19 virus might change and adapt like the flu virus does each year. However, although immunity does not mean non-infective, knowing what portion of the population is theoretically immune might help to lift the social distancing restrictions. There are ongoing debates about the best approach to start lifting these restrictions. For instance, antibody tests have been considered by some as a way to give “immunity passports”. In general, two strategies are confronting each other: the personal immunity vs. the immunity of a specific % of the population. Based on the recommendations made by their respective scientific experts, states will soon bear a high responsibility while choosing their immunity strategy for the deconfinement.
Anna currently serves as the Director of Governmental Affairs at IB Consultancy and Vice President of the CBRNe Society. Anna completed her studies with a Master’s Degree in International and Diplomatic Studies from the University of Trieste, with a Cum Laude honors award in 2015. She is managing the governmental affairs in the CBRNe Society, by building upon a vast network from her current work at IB Consultancy, in Leiden, The Netherlands. Her work in the international relations area started at the Austrian mission to NATO in Brussels, and has further developed with the start of her consultancy career in November 2015, which led to a specialization and management in governmental relations. Having contributed to the organization of the NCT Event series worldwide since the start of her consultancy career, Anna Paternnosto has maintained links with CBRNe experts and government officials in all ranks, throughout the world.
Ophélie currently serves as an Analyst at IB Consultancy. In 2019 she graduated from Sciences Po Lille with a Master’s degree in Strategy, Intelligence and Risk Management. She draws her expertise in security and international affairs from different working experiences at the French Ministry of Interior, the European Union Agency for Law Enforcement Cooperation (Europol), or the French Embassy in Belarus.