An affordable, scalable and highly sensitive testing approach based on the viral genome

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COVID-19 (coronavirus 2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause morbidity and mortality, despite mitigation strategies and vaccination efforts in Classes. Attempts by most countries to tackle COVID-19 have relied on social distancing, lockdowns, limited testing, contact tracing and vaccine deployment, all of which are now helping to fight the pandemic.

In an effort to minimize human suffering, economic costs, and restrictions on personal freedom caused by COVID-19, researchers from Germany and Austria have proposed an alternative method – effective genome-based tests based on COVID-19. on the population.

They demonstrated an affordable, scalable and highly sensitive viral genome-based testing approach developed as part of the Human Genome Project.

This test has been used to genotype billions of samples over the past decade. Here they achieved the same sensitivity and specificity, however, in a much more scalable manner and at much lower costs per sample (~ € 1 per PCR test for very high throughput). The researchers have also provided a link where they share the notes taken in the study, and the results are published on the medRxiv * preprint server before peer review.

Schematic of the high-throughput genome-based testing pipeline for SARS-CoV-2. (a) Sample tubes (barcode) are brought to test centers in 96-well racks from collection points (e.g., see Figure 2) and prepared for high throughput testing for the SARS-CoV-2 (or other viruses). Samples are heat inactivated prior to automated transfer to 384-well format (b) and preparation for (c) direct RT-PCR without the requirement of RNA extraction and (d) endpoint measurement showing results of the test (positive, negative).

“The procedure is EU-wide (European compliance) approved in gargle and swab-based versions and is already being used in Germany to test employees of Unilever and other companies,” the workers said. researchers in the document.

When discussing the test results, the researchers highlighted the main benefits. Infected individuals can be identified a few days earlier than with rapid tests based on the antigens currently in use. Early detection is a crucial prerequisite to stop the spread of the virus. Another advantage of this test is scalability.

“A single commercially available water bath PCR system with a capacity of 100 x 384 PCR plates per run would be capable of performing> 600,000 RT-PCR reactions per day, nearly three times the total PCR testing capacity.” currently available in Germany.

This approach can also be easily used to test for variants – with a second round of analysis with a small number of additional tests on samples positive for SARS-CoV-2.

“Despite these probable advantages and a first successful test of the strategy in Vò, an Italian city of 3,300 inhabitants, few governments seem to have seriously considered this alternative and, with the exception of Austria (“ Alles gurgelt ”), none appear to have supported the establishment of the required infrastructure.

For proof of concept, at the population level, Vienna, Austria approved a program aimed at interrupting chains of infection early and then tracing contacts to prevent the spread of SARS-CoV- 2. Individuals collected mouthwash samples themselves using a dedicated web application and verified them (www.lead-horizon.com). The researchers presented an overview (in 5 steps) of how population-level testing works in practice, as an example of the decentralized testing strategy used in Vienna.

A reliable PCR test result was guaranteed for every inhabitant of the community within 24 hours of sample collection. In this program, all residents have been invited to participate twice a week, as regular testing ensures that people with COVID-19 can be quarantined quickly and the chains of infection can be broken as soon as possible. Local pharmacies provided validated self-collection kits for mouthwash samples, making PCR testing accessible to all residents within a 5-minute walk. The samples were returned to the laboratory for transport, after having been packaged in sealed transport bags and transport packaging without danger for biohazards.

Population-wide testing logistics.  An example of the decentralized testing strategy used in Vienna.

Population-wide testing logistics. An example of the decentralized testing strategy used in Vienna.

Vienna provides free sampling devices to all residents, tourists and commuters. Due to its success, the program is currently being extended to more pilot regions in Austria to further assess more comprehensive national coverage. As an alternative, Alacris Theranostics has developed a similar kit that uses nasal swabs for high throughput testing.

Using a model based on the established Kermack-McKendrick theory, fitted for COVID-19, the researchers showed the effect of this population-wide testing approach on the development of the pandemic if it was adopted last fall. Moreover, assuming certain conditions and removing a few errors, they demonstrated that the model convincingly calculated “the efficiency of mass tests” – with moderate contact restrictions like those in Germany in early October 2020.

They suggested that “even the rise of the new variant of the British virus in early 2021 could have been brought under control by mass testing using highly sensitive PCR tests, removing the R-factor of 1.5 before testing began at very low levels for a high degree of participation.

Importantly, they highlighted this in relation to modeling the effect of the rapid antigen tests currently in use which only detect when an individual becomes positive after the onset of symptoms, which is quite late in the infectious phase.

From simulations conducted comparing PCR and antigen-based testing, this study indicated that population-wide PCR-based testing – even at a fairly low level of participation in Wave 2 (October 2020), carried out on a large scale could have resulted in a rapid drop in the number of infections. It would then be a question of managing the search for contacts.

To sum up, the researchers showed in this study that systematic population-wide screenings could eliminate COVID-19. However, noting the failure of urgent mass testing, they recommended that, in addition to vaccinations, this mass testing infrastructure could be activated and harnessed to respond to SARS-CoV-2 as well as other new agents. similar pathogens.

“The overwhelming majority of this impact, including nearly 90% of deaths, was caused by the second and third waves of the pandemic, and therefore could have been potentially avoided by mass PCR-based testing. “

Given the huge impact this approach could have had on the course of the pandemic, this raises the question of what mechanisms governments are using to assess potential solutions to problems of such enormous importance, should not be more. open and science-driven, the researchers write.

*Important Notice

medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information

Journal reference:

  • Evidence-Based Pandemic Preparedness: An Infrastructure for Population-Wide Genome-Based Testing for COVID-19, Hans Lehrach, Jon Curtis, Bodo Lange, Lesley A Ogilvie, Richard Gauss, Christoph Steininger, Erhard Scholz, Matthias Kreck, medRxiv 2021.06.10.21258526; doi: https://doi.org/10.1101/2021.06.10.21258526, https://www.medrxiv.org/content/10.1101/2021.06.10.21258526v1


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