Evan Lee, David Bell & Gerd Michel*
We’ve been hearing and reading a lot about the need to scale-up testing for COVID-19 and we’ve seen that early and widespread testing seems to have helped South Korea to “flatten the curve” relatively quickly.
Unfortunately, much of the world has seemed unprepared to carry out similar large-scale testing. Surprisingly, advanced countries like the US, France, Italy, Spain and the UK are struggling with this problem.
To better understand the questions around testing it is important to understand the different types of tests, how they work and what they are for.
Current types of COVID-19 tests
The first and most talked about tests are those used to determine if someone is actively infected with COVID-19. These are based on a technology known as real time RT-PCR (Reverse Transcription Polymerase Chain Reaction) which can detect the RNA strands that are the core of the virus.
This is a well-known technique that is in widespread use in many laboratories to diagnose commonly known viruses including influenza and HIV, and notorious ones such as Ebola, in addition to other RNA viruses. The technique works by replicating the single RNA strand of the SARS-CoV-2 virus (a single strand-version of the double stranded ‘DNA’ material that carries our genetic code), a sufficient number of times until there are so many copies that its presence can be detected through other chemical processes.
These tests require a sample to be collected using from the nose or throat, where infection first occurs, using an absorbent swab.
A second category of tests, based on blood samples, can be used to determine if someone has been infected recently or long ago by SARS-CoV-2. These are ‘serological tests’ that detect the body’s reaction to the infection, namely the antibodies that were produced by the patient’s immune system response.
These blood sample tests only become positive several days after infection and so are less accurate to diagnose infection in a sick person. But they remain positive long after infection has resolved, even if the person had been symptom-free and never knew they were infected. This information can be used to help make crucial decisions such as one’s ability to return to work, or whether they pose a risk for infecting family members.
Serology tests could also help determine the history of transmission of SARS-CoV-2 in a population – which in turn is important for determining if “herd immunity” has been reached and if the curve will remain “flattened” when control measures are reduced, and thus help us all to move towards returning to a normal life. On an individual basis, it may tell who has been infected and recovered, and therefore safe to return to the workplace without risking further illness, or transmission of infection to family members.
A third category, like serology tests but detecting a protein produced by the virus, rather than the infected person’s antibodies, is also being adapted for COVID-19. These work like pregnancy tests (that detect a protein from the growing embryo), but it is not yet clear whether there will be enough viral protein in samples for these tests to work to detect COVID-19.
For a new disease such as COVID-19, specific assays have had to be developed that target the virus and this takes time. It takes time to decide which types of test platform will best fit the task and then to develop the specific test on that platform.
Unfortunately, most of the world was caught unprepared because it turns out that the highly contagious nature of SARS-CoV-2 due to its very rapid passage from person to person calls for testing that can be done on the spot (“Point Of Care” – POC).
Most current RT-PCR assays are performed on larger machines that have to be installed in centralised laboratory facilities that require specimens to be transported and shipped, rather than on platforms that are suitable for use in health centres and clinics where patients turn up and results could be provided in minutes not days.
Innovation in test technology
From our many years of work in global health, we have also seen a range of innovative approaches to diagnosing and monitoring newly emerging viruses.
These include both new approaches to assays (e.g. genetic sequencing such as with nanopore technologies, and semi-mobile/low-throughput diagnostic platforms that are battery-powered and can be used in resource-limited settings where specimen transport is a challenge.
The emphasis in wealthier countries on centralised laboratory testing has left adaption of diagnostic technologies at Point Of Care as a relatively niche area reliant on small grants and philanthropic support.
Interest in POC testing rises temporarily when the need is acute, such as during the recent Ebola outbreaks, but wanes again as traditional global health donors and governments turn their attention elsewhere.
HIV stands out as an exception to this rule but there has been no investment to address other viruses that are also disease threats.
The emerging new innovative approaches address a testing gap that’s difficult for large, established companies to target. This is primarily because these companies have to answer to their shareholders who are more focused on the quarterly earnings picture and less on potential needs that may (or may not) materialise and prove profitable in the longer term.
South Korea made the news because it was able to rapidly develop and deploy RT-PCR-based testing. Other Asian countries have also been able to implement widespread testing much faster than the US and Europe.
The success of Asian countries in quickly deploying RT-PCR testing came down to a question of preparedness in multiple areas:
legal and policy frameworks that enabled government to move quickly to work with industry
testing platforms that could be adapted to the new assays that would be needed
experience of being foci of a number of recent outbreaks – SARS, MERS, H1N1, and
a strong public health infrastructure that could set up dozens of testing sites within days.
It’s also important to acknowledge other risks that can arise from a lack of preparedness. In a rush to expand testing capacity, Spain moved to procure 640,000 testing kits from a Chinese company only to find out that initial tests when implemented seemed to have achieved less than a 30% sensitivity to detect the virus. There’s a current round of finger pointing back and forth but the result has led to further delays.
Due to the high demand many tests have been quickly developed and introduced by companies with little or no expertise in diagnostics and/or on platforms that have not been validated according to stringent regulatory approval standards.
Remarkable lack of preparedness
Given the wake-up call that the SARS outbreak was supposed to give the world, the fear generated globally during the west African Ebola outbreak, and the frequently stated expectation in public health circles that more pandemics will arise (the movie ‘Contagion’ was not supposed to be science fiction), this failure to prepare is remarkable.
The technology exists for point of care testing. We can maintain massive military programs and have seen a record year on year stock market rise for the past decade. We have technologies to produce tests suitable for point of care.
Could it be that the same market approaches that have brought us unprecedented wealth have left us highly exposed to unplanned disruption? Biology does not respect the established way markets and economies have functioned.
Looking to the future, a middle ground needs to be found where the part of the profits generated by our economic system can be put side and used through a different model to protect that system from the weaknesses that have been so clearly been exposed.
The lack of investment in preparedness is costing us dearly.
Building preparedness for the future
To expand further we need to build on what we have.
The major for-profit diagnostics companies have the resources and expertise to both accelerate products to reach the market and to deploy them. Non-profits and small startups are often at the forefront of innovation coming out of academia but struggle to find sustained interest and support from donors and governments. They also have no capacity for the redundancy needed to be able to rapidly shift focus to a major new response.
While large corporations can manage such redundancy, it is at the risk of loss of competitiveness with rivals who focus primarily on commercial objectives. Nor is it aligned with quarterly earnings expectations of investors. Fixing this will take a willingness to absorb risk and to accept excess capacity in research, manufacturing and in raw materials which may well have a minor impact on earnings in most years. Addressing this challenge will take public intervention to give the private sector room to do this.
We hope that there will be recognition that it is critical to develop and invest in a global innovation ecosystem that links large, well-established players to maintain readiness without fear of losing out in the profit-focused market and also includes smaller actors that can provide the innovation they need to adapt.
We not only need to move quickly to meet the needs of the current COVID-19 pandemic (and no – it won’t be over by April or May), but to also build a new system of planning and readiness that can be ready for the next pandemic yet to come.
 It is estimated that 1/5th and 1/3rd of people infected do not show symptoms: https://www.researchgate.net/profile/Giuseppe_Lippi2/publication/340116806_Coronavirus_disease_2019_COVID-19_the_portrait_of_a_perfect_storm/links/5e79cf8f92851c309139234c/Coronavirus-disease-2019-COVID-19-the-portrait-of-a-perfect-storm.pdf, accessed 02/04/2020
 https://nanoporetech.com/, Accessed 04/02/2020
Ministry of Health; Chinese Embassy of Spain on Twitter; Sanidad devuelve lotes de test rápidos para detectar el coronavirus por su baja calidad, EfeSalud, 26/03/2020; Rueda de prensa tras la reunión del Comité de Gestión Técnica del Coronavirus; Los test chinos rechazados por España recibieron la homologación europea sin pasar ningún examen, Cadena Ser, 27/03/2020; La firma china que vendió a España los test defectuosos acusa a los médicos españoles de no hacerlos bien, Europa Press, 29/03/2020
Evan Lee is a Geneva-based consultant and an expert in global health policy. He has previously worked for pharmaceutical company Eli Lilly, the Foundation for Innovative New Diagnostics (FIND), Management Sciences for Health and Medicines Sans Frontieres. A medically qualified doctor by training, he has a BA in chemistry and physics from Harvard University, a medical degree from New York University School of Medicine and an MBA from Massachusetts Institute of Technology.
David Bell is an Australian-born and US-based public health physician, consulting in the development of global health technologies for community and point of care use. He previously led programs in product development and use at the WHO, Foundation for Innovative New Diagnostics (Geneva) and Global Good Fund (USA).
Gerd Michel spent more than 18 years with Abbott Diagnostics rising to the post of Director of Medical and Scientific Development for Europe, Middle East & Africa. Among his numerous product successes with high commercial impact were HCV, HIV and cardiac Troponin I tests that became state of the art diagnostics worldwide. He has worked at the Foundation of New Innovative Diagnostics (FIND) and is currently Chief Scientific Officer at Vela Research in Singapore, focusing on molecular and personalised diagnostics.