Team:Leiden

<!DOCTYPE html> iGem Leiden 2020

Rapidemic

We were not prepared for this pandemic

Coronavirus disease 2019 (COVID-19) broke out at the end of 2019 and was declared as a pandemic by the World Health Organization in March of 2020. It was clear that the world was not prepared. In many countries, the diagnostic response and introduction of social distancing measures were delayed, which resulted in overwhelmed health care systems¹. Within a couple of months, the obscure disease managed to weaken public health care systems, damage economies, and leave millions without a job ^2-5.

However, some countries responded quite quickly with effective measures, such as social distancing, lockdown, case detection, isolation, contact tracing, and quarantine of infected people, resulting in a relatively low number of cases. To implement the aforementioned measures, equipment was needed to test the infectious. However, low-income countries had limited access to equipment, such as PCR machines. Moreover, the increased need for testing reagents put a strain on the companies producing them, which also led to a shortage in high-income countries^6,7.

Even some of the most prepared countries could not keep up with testing. Increased sample collection, together with efforts to process tests and inform patients of their results, have overwhelmed laboratories ⁸. As a result, waiting times increased, which meant that people had to stay home for extended periods of time to await their results. This not only interrupted their daily life but in some cases also left them unable to earn money to support their families. Testing delays also made it more difficult to track the spread of the virus and contain it, as contact tracing was impeded. In March, this drove governments to institute national lockdowns, which separated families, shut down businesses, and left countless people without a job.

Cut the curve by testing

The COVID-19 pandemic demonstrated the importance of testing capacity, as isolating infected individuals is crucial to restrict the disease spread among the population. A limited testing capacity can result in underdiagnosis of infected individuals, creating an inaccurate estimation of actual infections during an outbreak. This poses a threat to disease-control and can steepen the curve. A rapid point-of-care testing kit like 'Rapidemic' would allow for faster and more frequent testing, which is essential to the containment of infectious diseases. The rapid diagnostic response will aid in controlling the outbreak and will cut the curve.

Why do current tests not suffice?

The current tests did not prove sufficient to contain an outbreak. There are 3 main categories of diagnostic tests: nucleic acid amplification tests, antigen-based tests, and antibody tests. These tests have their own benefits and drawbacks. A huge drawback of PCR-like nucleic acid amplification tests is the costly requirements: thermocyclers, laboratories, and skilled operators. ^9,10 Antigen-based tests on the other hand take a long time to develop, while a rapid diagnostic response is crucial ¹¹. Finally, antibody tests cannot be used in the early stages of infection, which means a negative result can be obtained, even though a person could already be contagious ¹².

How do we want to solve this?

We have developed a proof-of-concept for a label-free, easy-to-use diagnostic device. Our testing method is designed to detect the DNA or RNA of pathogens, thereby allowing for identification in the early stages of infection. Furthermore, it only requires the addition of primers to make the kit species-specific. This creates a modular design that can quickly and easily be adjusted to fit any pathogen. Our goal is to make our device accessible to everyone, regardless of geographic location. We are, therefore, working towards a user-friendly, point-of-care kit design to eliminate the need for a laboratory.

Future Prospects

COVID-19 will likely not be the last pandemic. Climate change, deforestation, and urbanization push humans and (wild) animals to live even closer together ¹³. This will enhance the likelihood of a zoonotic pathogen entering the human population ^14,15. Besides, increased globalization will further promote the spread of pathogens to epidemic or even pandemic proportions. Rapidemic would help us remain one step ahead and tackle this - yet unknown - pathogen. During this year of iGEM, we have gained substantial confidence in the potential of our kit and we are determined to build on this potential, to enable worldwide testing in the years to come!

Education & Public Engagement

Find out how we connected with the public and the scientific community, and shared our project in a global pandemic!

Human Practices

Here you can see how valuable insights from experts in the field of diagnostics helped us develop the Rapidemic project. To do so, we integrated opinions of stakeholders in the business field, researchers, doctors and patients, from around the world!

Engineering

The test's bio-molecular basis was designed and developed in a few rounds of problem solving. Eventually, we successfully connected three bio-molecular reactions to detect, amplify, and report the presence of a targeted DNA sequence.

Proof-of-Concept

The laboratory procedure of the detection technique was carried out in a prototype device to show how the technology holds the potential to be further optimized into a user-friendly point-of-care diagnostic tool. This gave insight into the duration and the cost of the test and pointed out several possibilities for the design of the hardware.

Model

An ODE-based empirical model was built to assess the performance of our technology, troubleshoot problems and guide future optimization of our technique. For instance, the model predicted how we could shorten the duration of the test, and it helped us in lowering the false-positive rate.

References

Khanna RC, Cicinelli MV, Gilbert SS, Honavar SG, M. G. COVID-19 pandemic: Lessons learned and future directions. Indian J Ophthalmol. doi:0.4103/ijo.IJO_843_20
Quiggin D. Green Industries Can Accelerate a True Jobs-Focused Recovery [Internet]. Chatham House. 2020 [cited 7 October 2020]. Available from: https://www.chathamhouse.org/2020/06/green-industries-can-accelerate-true-jobs-focused-recovery?gclid=CjwKCAjwzvX7BRAeEiwAsXExo-lWEpyILJY259WEQB4aL9Yyq_KOZTe-0WabYICNxmvEZBY8EXaTVBoCeQsQAvD_BwE
Smith E. Global stocks head for worst week since the financial crisis amid fears of a possible pandemic [Internet]. CNBC. 2020 [cited 7 October 2020]. Available from: https://www.cnbc.com/2020/02/28/global-stocks-head-for-worst-week-since-financial-crisis-on-coronavirus-fears.html
Alba S. The unemployment impacts of COVID-19: lessons from the Great Recession [Internet]. Brookings. 2020 [cited 7 October 2020]. Available from: https://www.brookings.edu/blog/up-front/2020/04/15/the-unemployment-impacts-of-covid-19-lessons-from-the-great-recession/
Coronavirus Disease 2019 (COVID-19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 7 October 2020]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/task-sharing.html
Mckinsey. COVID-19: Overcoming supply shortages for diagnostic testing. [Internet]. McKinsey&Company. 2020 [cited 25 October 2020]. Available from: https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/covid-19-overcoming-supply-shortages-for-diagnostic-testing
Brianna Abbot, Shortage of test components forces labs to beg, borrow and improvise. [Internet] Wall Street Journal. 2020 [cited 25 October 2020]. Available from: https://www.wsj.com/articles/shortage-of-test-components-forces-labs-to-beg-borrow-and-improvise-11586102401
Wooten, N. Georgia put some COVID-19 testing on ‘pause’ to allow labs to catch up, a health official said. [Internet] Ledger-Enquirer. 2020 [cited 25 October 2020]. Available from: https://www.ledger-enquirer.com/news/coronavirus/article242528876.html
Piepenburg, O., Williams, C. H., Stemple, D. L. & Armes, N. A. DNA detection using recombination proteins. PLoS Biol. 4,1115–1121 (2006).
Corman, V. M. et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance. 25, 2000045 (2020).
Peeling, R. W., Murtagh, M. & Olliaro, P. L. Epidemic preparedness: why is there a need to accelerate the development of diagnostics? The Lancet Infectious Diseases 19, e172–e178 (2019)
Kubina, R. & Dziedzic, A. Molecular and serological tests for COVID-19. A comparative review of SARS-CoV-2 coronavirus laboratory and point-of-care diagnostics. Diagnostics. 10, (2020).
5 reasons why pandemics like COVID-19 are becoming more likely [Internet] Gavi. 2020 [cited on 25 October 2020]. Available from: https://www.gavi.org/vaccineswork/5-reasons-why-pandemics-like-covid-19-are-becoming-more-likely
Wolfe, N. et al. Bushmeat Hunting, Deforestation, and Prediction of Zoonotic Disease. Emerging Infectious Diseases. 11(12), 1822-1827 (2005).
White, R. et al. Emerging zoonotic diseases originating in mammals: a systematic review of effects of anthropogenic land‐use change. Mammal Review. 50(4), 336-352 (2020).

[1] Khanna RC, Cicinelli MV, Gilbert SS, Honavar SG, M. G. COVID-19 pandemic: Lessons learned and future directions. Indian J Ophthalmol. doi:0.4103/ijo.IJO_843_20

[2] Quiggin D. Green Industries Can Accelerate a True Jobs-Focused Recovery [Internet]. Chatham House. 2020 [cited 7 October 2020]. Available from: https://www.chathamhouse.org/2020/06/green-industries-can-accelerate-true-jobs-focused-recovery?gclid=CjwKCAjwzvX7BRAeEiwAsXExo-lWEpyILJY259WEQB4aL9Yyq_KOZTe-0WabYICNxmvEZBY8EXaTVBoCeQsQAvD_BwE

[3] Smith E. Global stocks head for worst week since the financial crisis amid fears of a possible pandemic [Internet]. CNBC. 2020 [cited 7 October 2020]. Available from: https://www.cnbc.com/2020/02/28/global-stocks-head-for-worst-week-since-financial-crisis-on-coronavirus-fears.html

[4] Alba S. The unemployment impacts of COVID-19: lessons from the Great Recession [Internet]. Brookings. 2020 [cited 7 October 2020]. Available from: https://www.brookings.edu/blog/up-front/2020/04/15/the-unemployment-impacts-of-covid-19-lessons-from-the-great-recession/

[5] Coronavirus Disease 2019 (COVID-19) [Internet]. Centers for Disease Control and Prevention. 2020 [cited 7 October 2020]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/task-sharing.html

[6] Mckinsey. COVID-19: Overcoming supply shortages for diagnostic testing. [Internet]. McKinsey&Company. 2020 [cited 25 October 2020]. Available from: https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/covid-19-overcoming-supply-shortages-for-diagnostic-testing

[7] Brianna Abbot, Shortage of test components forces labs to beg, borrow and improvise. [Internet] Wall Street Journal. 2020 [cited 25 October 2020]. Available from: https://www.wsj.com/articles/shortage-of-test-components-forces-labs-to-beg-borrow-and-improvise-11586102401

[8] Wooten, N. Georgia put some COVID-19 testing on ‘pause’ to allow labs to catch up, a health official said. [Internet] Ledger-Enquirer. 2020 [cited 25 October 2020]. Available from: https://www.ledger-enquirer.com/news/coronavirus/article242528876.html

[9] Piepenburg, O., Williams, C. H., Stemple, D. L. & Armes, N. A. DNA detection using recombination proteins. PLoS Biol. 4,1115–1121 (2006).

[10] Corman, V. M. et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Eurosurveillance. 25, 2000045 (2020).

[11] Peeling, R. W., Murtagh, M. & Olliaro, P. L. Epidemic preparedness: why is there a need to accelerate the development of diagnostics? The Lancet Infectious Diseases 19, e172–e178 (2019)

[12] Kubina, R. & Dziedzic, A. Molecular and serological tests for COVID-19. A comparative review of SARS-CoV-2 coronavirus laboratory and point-of-care diagnostics. Diagnostics. 10, (2020).

[13] 5 reasons why pandemics like COVID-19 are becoming more likely [Internet] Gavi. 2020 [cited on 25 October 2020]. Available from: https://www.gavi.org/vaccineswork/5-reasons-why-pandemics-like-covid-19-are-becoming-more-likely

[14] Wolfe, N. et al. Bushmeat Hunting, Deforestation, and Prediction of Zoonotic Disease. Emerging Infectious Diseases. 11(12), 1822-1827 (2005).

[15] White, R. et al. Emerging zoonotic diseases originating in mammals: a systematic review of effects of anthropogenic land‐use change. Mammal Review. 50(4), 336-352 (2020).