Mar. 19 2020

Responding to the COVID-19 Pandemic

Patients without symptoms or mild disease often have low viral loads that may evade detection by standard tests. The C3 Test (Center for Infection and Immunity Coronavirus COVID-19 Test) is designed and optimized to be highly sensitive, or able to detect low levels of viral RNA.

CII has a strong track record identifying, tracking, and develop diagnostics for emerging infectious diseases. In 1999, Ian Lipkin and his team discovered West Nile virus, introduced the first sensitive diagnostic test for severe acute respiratory syndrome (SARS) in 2003, and in 2014 they identified the animal source for the Middle East Respiratory Syndrome (MERS) virus.

The C3 Test is similar to those seen on news reports: a person provides a nasal swab for testing. The turnaround, including RNA extraction and PCR, takes less than four hours. Because Dr. Lipkin’s lab at the Center for Infection and Immunity operates outside of a clinical setting, it can deploy the test for the development of prevention and treatment strategies and not just in-hospital situations when the patients are already ill.

Importantly, this new C3 Test can decrease both false negatives and false positives, reducing not only the number of people who unknowingly spread the virus, but also reducing resources spent on quarantining or treating those who are ill due to something else.

Current, less sensitive tests run the risk of a negative result when in fact the patient is infected; minimizing these false negatives is essential for control of disease transmission. In addition, the assay is very specific for this virus and doesn’t cross-react with other viruses resulting in false positives that would result in a patient being quarantined unnecessarily.

When used to identify individuals at risk for COVID-19 (because of possible exposure with an infected patient), the C3 Test will help identify a more accurate number of affected individuals and - most importantly - help stop the spread of disease by enabling COVID-19 patients to know their infected status. Moreover, the Lipkin team is working on multiple strategies for prevention and treatment and this diagnostic capability provides the foundation for these parallel efforts.


FAQ
 

WHAT IS THE NAME OF THE TEST?

  • CII COVID-19 Coronavirus Assay, also known as the C3 Test

Q: Who developed this test?
 

  • The test was developed by virologist and physician, Ian Lipkin and collaborators at the Center for Infection and Immunity. 

What makes the test(s) different from what exists or is being developed elsewhere?
 

  • This test is highly sensitive and accurate, with rapid results, and quickly scalable.

  • Infected patients without symptoms can spread the disease. This test was designed to detect low levels of viral RNA, which often may evade detection by standard tests.

  • Importantly, the C3 Test can decrease false results, reducing not only the number of people who unknowingly spread the virus, but also reducing resources spent on quarantining or treating those who are ill due to something else.

  • The test will identify a more accurate number of affected individuals and help stop the spread of disease.

Why is this test important, aren’t there many other tests developed already?
 

  • Most current tests are designed for those who are ill and showing symptoms. It is crucial we expand our testing to include those who may be infected and spread the disease without symptoms.

What are the names of the machines and what do they do?
 

  • Qiagen QIAcube HT Robotic Workstation, which helps automate the extraction of RNA from samples, and Applied Biosystems 7500 DX PCR system, which helps automate the polymerase chain reaction system.

  • Because of these machines, the C3 Test can be easily adjusted and modified if new strains of COVID-19 are identified which is necessary because as this virus goes through a population of people random mutations will occur (as they do in influenza viruses).

  • This makes it necessary for the assays to be easily modified over time by changing the proper reagents to continuously provide sensitive and specific results even as the virus changes.

Can you explain Qiagen QIAcube HT Robotic Workstation further?
 

  • Simply put, when samples come into the laboratory they are in the form of a cotton swab in a small amount of liquid or a blood sample, and the viral RNA must be isolated from the tube. The QIAcube automatically isolates the RNA from the sample, minimizing contamination and exposure of the worker to the material or contaminating the material.

What about the Applied Biosystems 7500 DX PCR system?
 

  • After the RNA is isolated, it must be converted into a more stable DNA that can be replicated for the testing using the Applied Biosystems 7500 DC PCR System.

How far into development is it, and what’s left to be done?
 

  • The test is complete, optimized and validated. The next phase is scaling workflow.

How does the lab's work align with government plans?
 

  • The Administration has altered requirements for FDA approvals, and we are cleared to proceed. CII tests will align with the White House’s current testing plans because the tests are able to adjust the sensitivity in the commercial instruments, which is important for at-risk individuals.

Have you gotten federal approval to implement testing or would this be handed over to the government?
 

  • The laboratory anticipates FDA approval this week, and then we would execute at Columbia University.

Who in the lab is working on this project?
 

Where will tests be available geographically?
 

  • The tests will run at Columbia University, where the CII lab is able to run samples from anywhere in the world, dependent on import controls.

  • It is also possible to replicate the system in other partner laboratories; for example, Dr. Lipkin is currently working with officials in China to provide them with this testing capability.

Will the tests be disseminated, or is the plan to invite care providers to send their samples to CII?
 

  • This is not a test kit that can be shipped. The test must be performed in a laboratory with the appropriate equipment.

Has there been any modeling to project/chart the spread of COVID-19 with the ability to test asymptomatic patients?
 

  • A paper published in the journal Science by Columbia Mailman scientists Jeff Shaman and Wan Yang demonstrates that it was the asymptomatic people that were responsible for most of the spread of the virus. Specifically, the researchers report:

◦ 86 percent of all infections were undocumented prior to the January 23 Wuhan travel shutdown;

◦ Per person, these undocumented infections were half (52 percent) as contagious as documented infections yet were the source of two-thirds of documented infections.

Who will be able to benefit from the test?
 

  • Although most of the samples run at Columbia will initially be from the greater New York City area, the lab will help others set up the platform to run in other states and countries. For example, during the Zika virus outbreak, CII made the assay available to the world to help stop the virus.

How do you plan to raise awareness of the test? How are you encouraging people to get tested?
 

  • CII is collaborating with partners globally to help educate people on the test, as well as explain the benefits of being tested.

  • Lipkin has also been featured in a number of media interviews giving his perspective on COVID-19 and the need for more specific testing.

How does this test work and what do patients need to do? Will it require any additional burden on healthcare staff?
 

  • Swabs will be taken as normal and submitted to CII. This fits into the normal workflow.

  • It can be part of a community testing program or part of a therapeutic intervention trial.

What other COVID-19 solutions are Ian Lipkin and his team working on?
 

  • Hydroxychloroquine (an antimalarial) as a preventative therapy for household members of patients who have tested positive for COVID-19.

  • Plasma therapy using blood from patients who have recovered from COVID-19. Recovered patients produce antibodies that can be used to treat other patients effectively.

  • Differential diagnosis of COVID-19 and influenza.

  • Genetic recombination of coronaviruses to understand the risk of mutations (that is what led to the original SARS, MERS, and the current COVID-19.

Who will own the right to the C3 assay?
 

  • The Columbia Mailman School will own the right to the C3 assay and will make it available in the public domain.