Some 10 months into the pandemic, testing for individuals who may be infected with COVID but who may not show symptoms remains a hodgepodge of methods, modalities, and technologies, many of which have not been authorized by regulators specifically to test asymptomatic patients.
Some insiders emphasize the importance of doing rapid turnaround testing of asymptomatic people at the point of care enabled by either antigen or molecular assays, while others contend that laboratory-based tests ─ whether molecular- or antigen-based ─ ought to be the modalities of choice.
But regardless of the modality, being able to identify asymptomatic patients in order to limit the number of people they may infect will be crucial to containing the pandemic, experts said, and both industry players and regulators are taking greater notice.
“Testing makes our enemy visible, so more asymptomatic testing gives us a better chance of getting infectious folks into isolation to avoid spreading the disease further,” College of American Pathologists President-elect Emily Volk said in an interview. “We know a high percentage of COVID-19 cases are spread by asymptomatic carriers, so quickly identifying them provides significant public health value.”
During the pandemic, testing has been focused heavily on people with coronavirus symptoms, partly because the demand has continued to exceed supply and the sickest people need to be prioritized. As tests have become more available, however, so too has testing of asymptomatic people.
In San Antonio, where Volk is co-chair for the city’s testing and laboratory reporting work group for the COVID-19 community response coalition, testing of asymptomatic people has been ongoing for months. Physicians and lab directors looking to test people who don’t have symptoms didn’t wait for regulators to authorize assays for that purpose.
“Some of the Emergency Use Authorization language for specific tests addresses whether or not they are appropriate for asymptomatic testing, but ultimately it is up to a physician to decide which platform they want to use for their patients and it is also up to public health medical directors to make those decisions for a community,” Volk said.
In the U.S., where authorizations for asymptomatic tests are on the rise, Hologic believes it is important that laboratorians and clinicians select high-sensitivity, nucleic acid amplification tests, Maurice Exner, its vice president of research and development and clinical affairs for the company, said in an interview.
At the end of September, the Marlborough, Massachusetts-based company received an updated FDA authorization to test people without symptoms.
The agency subsequently amended an EUA given to Hologic to include testing of people without symptoms.
Assays with especially high sensitivity “are needed when you want to screen people to identify who may be unknowingly transmitting the virus,” Exner said. “In so doing, you can minimize the number of outbreaks and better manage people in congregate living facilities such as nursing homes and prisons. The same is true for schools, where you also have a need for rapid detection of people carrying the virus before it spreads rapidly and have an exponential increase in infections.”
The FDA in June provided test developers with new EUA guidance on the validation processes it expects for the screening of asymptomatic people.
It recommended that a new test be evaluated in a clinical study of the intended population. The number of patients should be enough to detect 20 positive samples, with a positive percent agreement, or PPA, with a comparator test of 95%, and negative percent agreement, or NPA, of 98%.
“Though you need to compare the sensitivity of your test with that of a high-sensitivity assay, there is room for interpretation by test developers about what constitutes high sensitivity,” Exner said. “We would suggest you shouldn’t really have any leeway, and that the level of sensitivity of the comparison test be specified.”
Already a number of important use cases have emerged for asymptomatic testing that speak to the need for high-quality, high-sensitivity assays, Kevin Thornal, president of diagnostic solutions at Hologic, said in an interview. One example is screening by hospitals of people presenting for surgery. Additionally, hospital testing for COVID-19 is done in emergency and urgent care settings for people who may present with symptoms initially but whose symptoms subsequently subside.
These patients need to be tested to determine whether they should be isolated or allowed to return to normal activities, Thornal said.