By Aaron J. Dy, PhD, Senior Analyst; John Latimer, Senior Analyst; Alexandra Dekkers, Analyst; Kristine Mechem, PhD, Vice President; Donna Hochberg, PhD, Partner
Like few other events in history, the COVID-19 pandemic has highlighted the criticality of diagnostic testing for efficient and effective delivery of clinical care and management of public health. Public health officials have stressed that early and broadly available testing enables contact tracing, isolation of affected individuals, and more effective public health planning. Test volumes and rates are daily national and global news headlines as countries have mobilized to handle the spread of the SARS-CoV-2 virus. However, there has been significant variation in how countries have approached SARS-CoV-2 test roll-out leading to differences in subsequent testing rates and clinical and public health impact.
In particular, commentators have been aggressive in highlighting early (and ongoing) struggles with US testing for SARS-CoV-2, including technical manufacturing issues with a CDC developed test and frustration from labs that could not get authorization to use independently developed tests. Meanwhile, some countries, including South Korea and Germany, have received positive reviews for high early testing rates.
The US has clearly trailed both South Korea and Germany in per capita testing. In fact, the US had lower overall test numbers than South Korea through most of March despite both countries having first confirmed cases on Jan. 20, 2020. Such delays can directly impact the effectiveness of a country’s overall response and containment efforts.
In this blog post, we utilize comparative data (as seen above) to posit recommendations for how the US can more effectively manage future SARS-CoV-2 outbreaks.
How did South Korea and Germany achieve high testing rates?
In May 2015, a 68-year-old man returning to South Korea from the Middle East was diagnosed with MERS (Middle East Respiratory Syndrome) leading to an outbreak. In total, 185 laboratory-confirmed cases and 38 deaths were recorded. Compared to COVID-19, these may seem like small numbers, but it was a wake-up call to Korean officials who saw cumbersome testing and a lack of data as the outbreak began. Learning from this experience, South Korea built an epidemic response plan to:
- Engage commercial test manufacturers early,
- Free the South Korean CDC to authorize unlicensed tests, and
- Publish precise contact tracing from patient testimony, GPS data, CCTV, and other sources.
This plan was put into action in 2020 after the World Health Organization (WHO) released details of the spread of SARS-CoV-2 within Wuhan, China.
South Korea reported its first confirmed SARS-CoV-2 patient on January 20th. On January 27th, the South Korean government met with commercial partners to begin mass production of a SARS-CoV-2 test modeled after the WHO-validated test. A week later, the Korean CDC approved the first diagnostic test for use. South Korea approved test kits from Seegene (Allplex 2019-nCoV Assay with a TAT of 1 hour), Solgent (DiaPlexQ Kit with a TAT of 4 hours), SD Biosensor (STANDARD M nCoV Real-Time Detection Kit with a TAT of 1.5 hours), and Kogene Biotech (PowerChek Novel 2019 Coronavirus Assay with a TAT of 1 hour). South Korea quickly set up drive-thru testing facilities to improve access to these tests and delivered testing kits to hotspots within the country (e.g., Gwacheon-si, the location of the Sincheonji Church of Jesus outbreak). Ultimately, the government leveraged lessons learned from a recent outbreak to mobilize resources and appropriately contact and isolate infected patients.
Germany took a slightly different approach, heavily leaning on broad expertise in laboratory developed tests (LDTs). On January 10th, a German biotech company, TIB Molbiol Syntheselabor GmbH introduced the first viable diagnostic kit outside of China and sold it to the WHO and countries around the world. Shortly thereafter, the protocol for developing this kit was distributed to all German laboratories, which allowed a fleet of more than 85 labs across the country, with uniquely strong expertise in virology, to develop a test. By mid-February, other labs had developed their own LDTs specific to SARS-CoV-2, allowing for significant testing capacity before the outbreak hit Germany in late February. Patient access to testing early in the outbreak allowed Germany to identify asymptomatic patients and enabled local governments to track contacts of known positive patients. This was in stark contrast to the situation in the United States, where a shortage of tests limited testing to severely ill patients and was followed with little to no contact tracing.
However, decentralization came at a cost, and Germany struggled, albeit less than the US, with data aggregation and delivery of results to patients/patient contacts. Germany realized contact tracing, as implemented within South Korea, was an effective method to reduce the spread of disease (barring the draconian measures seen in China). With a solid testing foundation, Germany took action to operationalize contact tracing through the Fraunhofer Heinrich Hertz Institute. This organization is leading the Pan-European Privacy Preserving Proximity Tracing (PEPP-PT) initiative to develop an app to contact people who have been in close contact with a positive patient (the app is to be released at the end of April). The app uses Bluetooth to log a user’s proximity to other cellphones, then anonymously contacts everyone who was previously close to a positive patient. Innovative methods for contact tracing are imperative as the US and EU balance privacy regulations and public health measures.
Ultimately, South Korea and Germany implemented early testing, operationalized testing logistics, sent results to a centralized database, and tracked contacts of known positives to decrease the spread of SARS-CoV-2.
What was the US testing response to COVID-19?
The US began its SARS-CoV-2 testing efforts with a kit developed by the CDC. The CDC distributed test kits in early February, but labs reported technical issues with negative controls resulting in failed outcomes. As labs worked to independently develop higher quality tests, they faced regulatory hurdles that delayed use. Specifically, FDA, CDC, and CMS did not grant authorization for any emergency use tests beyond the one CDC option for some time. In addition, the CDC confirmed there was no need “to bring commercial labs quickly into the testing mix.” The decision to restrict testing to the CDC test proved costly as batches of the kits were faulty (manufacturing issues) and the CDC lab itself was neither prepared to scale up for national scale testing or capable, due to its size, of providing the needed volume of testing.
This led to US testing protocols and capacity falling significantly behind virus transmission rates which in turn has led to an overall greater need for higher testing volumes to occur and a need to quickly ramp up testing capabilities to meet this high demand.
On February 29, the FDA issued updated guidance on Emergency Use Authorization (EUA) for LDTs. High-complexity certified labs could begin using analytically validated1 (see footnote for analytical vs clinical validation) LDTs before a review of their EUA submission. On March 16, the FDA authorized individual states to take responsibility for LDTs within their borders. Commercially developed instruments and reagent kits were also given the green light to be distributed for use prior to the FDA granting an EUA.
With a clearer and faster regulatory process now apparent, diagnostic product manufacturers and numerous other laboratories jumped in to begin providing testing. However, as of March 15, only the CDC (molecular viral RNA LDT), New York Department of Health (molecular viral RNA LDT), Roche (molecular viral RNA kit for the 6800/8800 high throughput automated lab analyzer), and Thermo (molecular viral RNA kit for the ABI 7500 high throughput automated lab analyzer) had EUAs for SARS-CoV-2 testing. By March 31, there were 22 tests with an EUA and another 220 test developers had notified the FDA of the intention to submit an EUA. As of April 15, those numbers stood at 36 and 315, respectively.
With more tests available, US testing capacity and performed tests began to drastically increase. A report from former FDA commissioner Scott Gottlieb and others estimated that the US would need at least 750,000 tests/week to enable necessary public health measures to control this virus and that number was only finally achieved in early April. (Note: There remains much debate about whether this number is sufficient to control the public health crisis. At the time of writing, we believe a significantly higher number of tests per day will be needed to return to “normal”, including enough testing to allow pre-return to work testing of asymptomatic individuals.) Some states, such as New York or Louisiana, have performed more testing, on a per capita basis, than the national average driven largely by the allocation of resources to these hotspots.
While the US has started to build up testing capacity, there has been a clear lag versus what was and is needed to enable broad testing and contact tracing. The management of future outbreaks of SARS-CoV-2 (and someday other new viruses) within the US will rely heavily on quickly operationalizing testing capabilities.
While there is no perfect comparator to the US in terms of geography, demographics, politics, or healthcare infrastructure, there are key lessons the US can learn from how South Korea and Germany enabled high rates of SARS-CoV-2 testing including the importance of:
- Engaging industry partners early to develop more testing options more quickly, rather than relying on just one test (e.g., CDC test)
- Coordinating a national response with government officials (local and national), regulators, labs, and diagnostics OEMs to identify bottlenecks in assay development, testing capacity, and testing logistics (e.g., sample collection kits, trained technicians, placement of relevant instruments, ancillary supplies) and quickly determine how to allocate resources
- Giving guidance to labs and companies developing tests to ensure best practices and broad dissemination and sharing of key learnings
- Ensuring test capacity is broad to identify more infected individuals more quickly
- Centralizing and streamlining data collection to enable contact tracing and provide a resource of reliable national data and enabling more effective, and less economically damaging, quarantine patterns
Once a country falls behind tracking the spread of a virus, as the US did, it is difficult to understand the severity of the spread and many opportunities for prevention are missed. For example, the US still largely relies on volunteer efforts to collect comprehensive testing data, and there remains limited follow-up with confirmed patients or their contacts. By understanding the differential virus management responses around the globe, the US can ensure an effective response to the next outbreak.
1 Analytical validation demonstrates the accuracy, precision, and reproducibility of a test. Clinical validation demonstrates the effectiveness of the test and requires more robust clinical trial data.