Clinician experts who are elected leaders in the nationwide Infectious Diseases Society of America (IDSA) on Tuesday, April 7, shared their perspectives on the current moment in the COVID-19 pandemic, especially around testing issues, in an early-morning telephonic and web press briefing. As the association describes itself on its website, IDSA is “is a community of over 12,000 physicians, scientists and public health experts who specialize in infectious diseases. Our mission is to improve the health of individuals, communities, and society by promoting excellence in patient care, education, research, public health, and prevention relating to infectious diseases.” IDSA has been outspoken on COVID-19-related issues, urging a “continued commitment to data-driven responses to the coronavirus,” supporting the opening of access to convalescent plasma use, and urging that the federal recommendation on sheltering remain in place for the time being.
Christopher D. Busky, CEO of the IDSA, moderated the discussion, with two presenters. The first, Angela M. Caliendo, M.D., Ph.D., FIDSA, is a professor and executive vice chair in the Department of Medicine at Alpert Medical School, Brown University, in Providence, Rhode Island, and is secretary on the IDSA Board of Directors. Kimberly E. Hanson, M.D., M.H.S., is an associate professor in Internal medicine at the University of Utah School of Medicine and an adjunct associate professor in pathology at the University of Utah School of Medicine, in Salt Lake City.
For background, on March 17, IDSA had released a statement on diagnostic testing for the COVID-19 virus. In addition to articulating which patients and individuals should be prioritized for testing, the society made the following statements about testing that were operative at that time (since then, testing availability and capability have opened up somewhat).
IDSA noted the following, as “Currently Available COVID-19 Diagnostic Tests and Limitations:
> Send testing to CDC or state/local public health laboratories: Limitation: significant delays in deployment of testing. Delays patient care and containment measures and leads to inefficient use of scarce resources such as negative pressure rooms and personal protective equipment (PPE).
> Send testing to commercial reference laboratory. Limitations: turnaround time and cost not yet defined.
> Develop local, hospital-based tests (LDTs). These tests may be based on the CDC, WHO, or manufacturer assays or created de novo. Limitation: Laboratories pursuing this route must perform an assay validation and pursue an FDA Emergency Use Authorization (EUA). The recent FDA guidance allowing laboratories to use validated tests while their EUA is under review is very helpful, yet still portends an excessive regulatory burden. Further, many reagents, primers and other components needed for LDT assays are on back-order.”
In the context of ongoing complexity around testing, Drs. Caliendo and Hanson spoke in turn, and then responded to questions from the telephonically assembled press.
“I’d like to start by giving you a perspective on how COVID has impacted my life and those of my colleagues,” Dr. Caliendo began. “I did infectious diseases consults last week for all types of patients. This week, I’m back to my admin role at the hospital trying to determine a surge plan for our internal medicine group. And I’m working with our admin team on trying to apply for grants; working on telehealth. Our life has become all-COVID all the time.”
Meanwhile, “What we want to talk about today is testing,” Caliendo said. “I want to first describe the two general types of tests. The first is what people are referring to as rapid tests; those are molecular tests, PCR-based [polymerase chain reaction-based], that can detect the virus in a clinical specimen. That’s what we’re using right now for diagnosis. The other type of test is a serology test, which gives you an idea of antibodies [As the Center for Health Security at the Johns Hopkins Bloomberg School of Public Health explains it, “Serology testing for SARS-CoV-2 is at increased demand in order to better quantify the number of cases of COVID-19, including those that may be asymptomatic or have recovered. Serology tests are blood-based tests that can be used to identify whether people have been exposed to a particular pathogen by looking at their immune response. In contrast, the RT-PCR tests currently being used globally to diagnose cases of COVID-19 can only indicate the presence of viral material during infection and will not indicate if a person was infected and subsequently recovered. These tests can give greater detail into the prevalence of a disease in a population by identifying individuals who have developed antibodies to the virus.”] These are not as useful in an acute setting as they are later on in terms of who has been exposed to the virus or not.”
Further, Caliendo said, “How do these tests get through the regulatory system and into the hands of clinicians? When the national emergency was announced, that allowed the FDA to activate its emergency use plan or policy. Typically, there would be two phases: one would be accepting a test through the use of mock specimens, doing tests to determine how sensitive the test is, etc. And then you would do a clinical study with patients who have and don’t have the particular disease. There’s both a clinical and an analytic component. In an emergency, the FDA requires companies to do the analytic testing of a test, but not the clinical. And here we don’t know how good a test is, because we don’t have the time to run the clinical trials.”
Indeed, she said, “That’s why we have some data but not the full picture. We have nearly two dozen tests now for COVID that have been approved. Our clinical lab in our hospital is using two different tests and are looking to bring up a third. And just yesterday, CVS has started drive-by testing with another test. So I could be seeing patients who have had tests done with four or five different commercial assays. And it’s unlikely that all 24 of these tests will perform exactly the same way.”
Caliendo went on to note that obtaining a good specimen is “absolutely critical”—and is far from guaranteed. Another issue, she noted, is “where people are in the illness. If you test me on the first day I have symptoms, the amount of virus in my nasal tract will be low compared to four or five days later, when I’m at the peak. So the biology of the case impacts.” And, she noted, the third issue is “the quality, the sensitivity of the test itself. And we’re relying on the FDA and the emergency authorization process to make sure these tests have at least an analytical sensitivity.”
Further complexity around testing
“Like Angie, I’m an infectious diseases doctor, so I split my time between seeing patients in the hospital and diagnostic testing,” Dr. Hanson said. “Almost every waking hour in the past four or five weeks has been spent trying to get multiple tests up and running in our lab. And people ask me, why would you have multiple tests? A couple of considerations: one is having rapid tests—a test that generates a result rapidly—in under an hour—is the ideal situation, to inform management who are really, really sick. Then there are folks in the community with symptoms but who not sick enough to come into the hospital, and we want to have tests that can run in parallel for them. We decided to support two EUA [Emergency Use Authorization] tests for redundancy. The other thing is as an ID specialist and a microbiologist, I’ve spent a lot of time coordinating with our local and state health departments and other hospital systems in our region. Our goal is to test everybody in the community who has symptoms. This really informs who needs to be at home in isolation/quarantine, how long they need to be in strict quarantine, and it will allow the health department to do contact tracing on them.”
What’s exciting, Hanson said, is that “We now have almost two dozen EUA-approved tests. Early in the outbreak, testing capabilities were quite limited; now we’ve got multiple options to choose from. We were fortunate early on to partner with a commercial tester, so we would have test kits. Now, we’re facing shortages of other elements. So as an example, per the sample types, you need collection devices like swabs. That has been problematic for us; we’ve faced serious shortages of the swabs, of the media you put the swab in, of the tubes you put the media in. Also, depending on which test you choose, the manufacturer may only supply parts of the test. So we have colleagues faced with shortages of the reagent, which helps you get the virus out of the clinical sample and put it into the test to amplify it and verify it.”
The physicians were asked a number of questions by the press. One was whether individuals who have recovered have some level of immunity, and whether patients should be tested to see if they’ve fully recovered. “That depends on where you’re discharged to,” Caliendo said. “When we discharge patients to home, we do not test them a second time. We instruct them to separate themselves from family members; but we don’t test everybody on the way out the door. One reason is that we don’t have enough tests, and have to prioritize, as Kim said. But also, the test we use for the virus detects the RNA for the virus. And we know from our experience from influenza, that you can have a positive test much longer than you’re infectious. A PCR may be positive much longer than the culture itself. Second, patients cannot be sent back to a nursing home without two negative tests, and that can take weeks, depending on how sick they are.” And do those who have recovered have some level of immunity? “We don’t know that,” she responded.
In response to a different question from the press regarding why Utah has been relatively successful in its testing, Hanson responded, “We have been in a pretty unique situation here in Utah. A majority of the population lives along the mountain range, with very close connections to the university hospital and the main private hospital system. As an academic medical center, we’ve built a good testing system. But partnering with Intermountain Health, who has the vast majority of outpatient population, for them to collect the samples and send them to us, has been a great example of partnership. And our health department has been extremely helpful in helping to facilitate that at the state level.”
What about the ability to test broadly in communities? “The virus has hit different parts of the country at different times; and not all clinical labs can perform all the tests,” Caliendo said. “Some are more sophisticated to perform, some easier. That being said, in addition to testing people who are about to be hospitalized, testing people out in the community would be very, very helpful. We don’t have enough tests in RI to test everybody who’s symptomatic, but we’ve been ramping up tremendously, and our governor has led in this area. So we’ll get to the point that we’ll be able to test everybody who’s symptomatic, and that would be very helpful. And just because you have a negative test doesn’t mean you can go out and do anything. You still have to wear a mask in public and assume you could be infected. If shelter in place is lifted too quickly, we’ll see another wave of infections.”
Asked about what the current wait times are to obtain test results, now that commercial and other labs have received approval to do testing, Caliendo responded, “That depends on which test you use and where it’s done. The drive-by clinics are running a test that can give you a result as quickly as a half-hour. One of our test methods in our hospital takes an hour, the other takes three to four hours. The department of health one takes five to six hours. The question is, do we have reagents that day? We still have backlogs, which means waiting days,” she said.
And added Hanson, “Some of the larger reference labs early on were some of the only places offering testing to multiple patient care organizations, but as we’ve had more EUA-approved tests and multiple labs are involved, the wait times have gone down, assuming we have access to reagents and collection devices.”
And, per challenges with obtaining reagents and with backlogs in testing, Hanson noted that “We’ve been sharing supplies with Intermountain.” And Caliendo noted that “We’ve pushed as much [care delivery] as possible to telehealth. And the offices typically have swabs. So that was helpful. We did go through ups and downs with swabs. We seem right now to have an adequate supply. As we expand testing to drive-by sites, it will become very important to keep track of supply.”
Asked about the possible lessons learned from the experience of South Korea, where the government moved very early to execute massive nationwide testing in order to find positive individuals, while at the same time moving quickly on a stay-at-home policy on a national level, Caliendo said, “It shows you the importance of testing. Several South Korean companies provide testing reagents internationally, so they were well-poised to get testing running quickly, so it made a difference. There are areas of this country that haven’t peaked yet, so we might be able to impact the epidemiology there, in contrast to places like New York and Detroit and Los Angeles that are already peaking. So you could theoretically implement a different type of strategy in those areas. You could imagine that in regions, you could mimic what South Korea did. But I do think that the testing they did in South Korea was very important in controlling their outbreak.”
