As soon as it became clear that a spreading viral illness was poised to reach all corners of the globe in 2020, the virologists and infectious disease experts at Roche went into action. They designed a polymerase chain reaction (PCR) assay in January, with a mid-March launch.1 Although turnaround time on a test like this can often take longer, the Roche team pulled it off in two months given the urgency of the situation, according to Daniel Jarem, PhD, Roche’s Medical Affairs Manager for on-market evidence generation for virology PCR solutions.
“There were only seven [novel coronavirus 2019] sequences in the database, yet our team was able to put together a very specific and sensitive assay,” said Jarem. “Using a dual-target approach, the test is designed to cope with genetic diversity and ongoing evolution of the virus, and data suggests we have one of the most sensitive and robust assays on the market.”2 Results from this assay can be transmitted to healthcare providers and patients in a matter of hours,1 enabling patients who test positive to immediately take steps to isolate themselves and prevent further community spread.
It’s this kind of proactive skill and collaboration that has enabled Roche and GE Healthcare to be at the forefront of tools to manage COVID-19, from RT-PCR testing for active infection to blood tests that detect antibodies generated by past infection. The team now hopes to incorporate its testing capabilities into digital solutions that will aggregate data, optimize patient care and support healthcare resource management.
Testing is the Key First Step
One of the biggest confounders of the COVID-19 pandemic has been how to interpret test data. As many people seek tests to determine if they have an active infection, sensitivity—or the ability to catch true positive cases—is most important, according to Jarem. “Although our RT-PCR test has high specificity, it is noteworthy that in the current pandemic the clinical impact of a false-negative during diagnosis is greater than a false-positive,” he said. “Sensitivity and speed to a result can combine to help identify patients who may need to be admitted to the hospital and given supportive treatment.”
Some people who have symptoms of COVID-19 do not test positive to assays; however, this does not mean they were never infected but possibly that the window during which the presence of the virus would have been detected has passed, according to Michael Hombach, MD, Global Clinical Leader Infectious Diseases at Roche Diagnostics CPS.
Recognizing the need to know who in a community had been infected, Hombach led a team that quickly profiled a highly accurate test for antibodies to the virus, indicating an immune response.3 “As early as the end of February, it became clear that we would need a tool to detect past infection with high specificity,” he said.
The Roche serology antibody test has a specificity of 99.8%.4 That means the test generates almost no false-positives; those who test positive almost certainly do have antibodies to SARS-CoV-2 and no other virus.4 “Therefore, we focused our target product profile very much on using this test at a population level. If there is a generally low level of virus circulating in an area, you need very, very high specificity to have a good positive predictive value.”
The Roche antibody test detects high-affinity antibodies, providing a more accurate result than tests that also capture low-affinity antibodies.4 The test also demonstrated no cross-reactivity to common cold coronaviruses in testing, meaning it doesn’t register non-COVID antibodies left over from previous viral illnesses that could skew results.4
Because it’s unclear right now whether a positive antibody test means a person has created enough antibodies to render them immune to SARS-CoV-2 for any length of time, scientists are looking at antibody testing to be used as a form of community surveillance that can help guide lockdown measures.
Testing in an Acute Care Setting
While testing isn’t perfect, it remains a valuable tool to assist clinicians. For example, if a patient shows up at an emergency room with severe vomiting and diarrhea, he or she likely will be tested for SARS-CoV-2. If the assay is negative but the antibody test is positive, that’s a solid clue that the patient was infected with the virus at some point. If the antibody test is negative, it’s possible that the patient was infected but the antibody response has not yet begun. The major questions are this: Are the patient’s symptoms a result of infection with SARS-CoV-2, or is this another malady entirely? And, if it’s COVID-19, how likely is this patient to deteriorate?
Here’s where physicians need to look at a multitude of variables. Aiding in the diagnosis and assessment might be other clinical symptoms such as cough or fever; x-rays or CT scans showing lung inflammation; patient history such as travel to a SARS-CoV-2 hot spot or known exposure to an infected person; and blood tests that look for rises in certain biomarkers such as interleukin-6 (IL-6), which can presage respiratory failure, or D-dimer, which indicates blood clotting.
“We need to look at these key markers that can support this two- or three-day period between infection and positive test results,” said Peter Ramge, PhD, senior international medical affairs manager at Roche. “It’s also helpful because the virus stops shedding after seven or eight days, and then you can’t find the virus in the tissue.5” Because of the virus’ cycle, repeat testing of patients is important in order to capture the true picture of infection.
Digital Solutions Can Fill in Testing Gaps
To make the best use of the information provided by these key markers, scientists and technology experts are working together to create digital collaborative tools that assist providers in pulling together patient data. These tools, aside from being one-stop shops for information, rely on analytics that alert providers to the possibility of patient decline.
“If someone comes into the hospital in the second or third week of their illness and they’re deteriorating, we want a digital solution to help providers interpret test results,” said Tyler O’Neill, PhD, Clinical Science Leader, Acute Care at Roche. “We need a digital solution that can improve diagnosis, management, and follow-up.”
According to O’Neill, one could imagine a digital tool that could aggregate data, like a clinical assistant, and potentially enable the management of patient care across provider teams.
The goal of such a tool would be to help providers get a full picture of a patient’s COVID-19 status and help clinicians keep tabs on multiple COVID-19 patients. The hope is that with the right digital tools, teams could reduce variation across various workflows and gain in efficiency.
Because COVID-19 is so new and the knowledge base is evolving, teams can envision a clinical decision support solution that could guide users as they care for their patients, helping them decide what questions to ask or what diagnostic tests may be needed.
Experts say a streamlined product that syncs data among healthcare teams and enables swift access to real-time test results could be a game changer when it comes to the diagnosis and management of COVID-19 patients.
“Providers would be able to react more nimbly with a tool like this in their hands,” O’Neill said. “
1. Roche.com. Roche’s cobas SARS-CoV-2 Test to detect novel coronavirus receives FDA Emergency Use Authorization and is available in markets accepting the CE mark.https://www.roche.com/media/releases/med-cor-2020-03-13.htm Accessed on June 30, 2020.
2. Roche.com. cobas® SARS-CoV-2 Test. https://diagnostics.roche.com/global/en/products/params/cobas-sars-cov-2-test.html. Accessed on June 30, 2020.
3. Roche.com. Roche highly accurate antibody test for COVID-19 goes live at more than 20 initial lab sites in the US. https://diagnostics.roche.com/us/en/news-listing/2020/roche-highly-accurate-antibody-test-for-covid-19-goes-live-at-more-than-20-initial-lab-sites-in-the-us.html Accessed on June 30, 2020.
4. Roche.com. Inside Roche Diagnostics’ approach to antibody testing. https://diagnostics.roche.com/us/en/roche-blog/antibody-testing–the-next-step-in-the-fight-against-covid-19.html. Accessed on June 30, 2020.
5. World Health Organization. Criteria for releasing COVID-19 patients from isolation. https://www.who.int/news-room/commentaries/detail/criteria-for-releasing-covid-19-patients-from-isolation. Accessed on June 30, 2020.