The laboratory tests of pandemic summer

Also “completely fascinating,” she continues, has been the vendors’ control of utilization. She has to keep one vendor apprised of how many tests and plates the lab runs, for example, “because they want us to run only full plates. So I’ve got to wait until I have 96 specimens before I run it.”

Vendors track this daily, she says. “They know how many plates they gave us and how many plates we ran, and if we ‘wasted’ any, meaning we didn’t get a test result because we put a plate in partially empty.”

“You can see that this would be a turnaround time problem,” she notes. The onus is on Dr. Fuhrman to manage TAT expectations, particularly for pre-op cases. “If I get a specimen in the lab late Wednesday and have a partial plate, I still have to figure out how to get it tested that night.” Fortunately, she has four other platforms among which to juggle specimens.

But it’s a differential equations nightmare, she says. It’s constant. “And it just gets harder because the volume keeps going up.” Although there has been some sense—in Ohio, at least, at the start of the summer, that “we’re past the bad part”—that is, spring—“from a testing standpoint we’re in the midst of a challenge, the likes of which we’ve never seen before.”

The inability to obtain reagents has also weighed heavily on Thomas Williams, MD, a pathologist formerly with Nebraska Methodist Hospital, who subsequently served as chief medical officer and director of the Division of Public Health for the Nebraska Department of Health and Human Services. Recently retired, he unretired when the COVID-19 crisis hit this spring. “Just helping out,” as he puts it, as a pathologist familiar with public health.

When he began helping support the state’s response to the emerging pandemic, Dr. Williams surveyed laboratories to get a sense of who would be able to perform tests. The answer seemed promising: There were numerous instruments across the state, not only along Interstate 80, but in smaller communities.

That bit of good news was tempered by another response: “No one—no one—had any reagents,” Dr. Williams recalls. For weeks, the only COVID-19 testing capacity was in Omaha.

More recently, more devices and reagents are being brought into the state by the federal government, he says. But at institutions that already had an analyzer in place, reagents have remained scarce. One vendor told Dr. Williams that a site he was inquiring about “will get reagents in ‘a few months,’” Dr. Williams says. “The reagent supply in the field has been very, very spotty.”

One of the more pressing problems of the pandemic is that its overwhelming nature has meant no one has had time to think. “We’ve all been reacting,” Dr. Nolte observes. That includes trying to stay on top of the unending stream of information that appears in all its forms, including medRxiv. “That website is really complicating my life,” Dr. Nolte jokes.

No study, it seems, is too small to inspire well-intentioned hope. “Someone gets ahold of it—it could be a researcher, it could be a hospital administrator—the next thing I know, I’m responding to it,” says Dr. Nolte. Hence the stream of studies filling his inbox that involve four patients and somehow conclude that saliva is better than an NP swab.

“What am I supposed to do with that?” Dr. Nolte asks. Even the high-quality, peer-reviewed journals are pushing out information with head-spinning speed. He serves on the editorial board of several journals, “and I know the pressure they’re under to turn things around quickly. The journals are racing to publish data that they think will be interesting and of value. But there’s a fine line you walk between putting information out that you might not be so comfortable with in normal circumstances, and balancing that against the need to know.

“I don’t have a good answer for that, either,” he says.

Equally frustrating, Dr. Nolte says, is that he has researchers “clamoring to gain access to specimens. I know that’s part of my job; I know it needs to be done. But it can’t be done now.”

“There’s so much data that’s flowing by,” he adds, “and so many opportunities to do things that would be of interest and value are just slipping away.” (Despite the crunch, he and colleagues with the infectious disease subdivision leadership of the AMP wrote a perspective piece for the Journal of Molecular Diagnostics [Nolte F, et al. doi:10.1016/j.jmoldx.2020.06.003] about responding to SARS-CoV-2 and future pandemics.)

Dr. Fuhrman comes up equally empty-handed as she digs for answers. By early June, her institution had tested some 13,000 asymptomatic patients, with a positivity rate of 0.22 percent. “Is that the right use of our test?” she asks. “I don’t have an answer to that. I don’t know anything about those patients—I just have the statistics. And nobody has the manpower right now to be cranking out clinical studies on this.

“We’ve got to have some people with the bandwidth to take a breath and start reviewing charts and determining who really has COVID,” she continues, echoing Dr. Nolte’s earlier concerns about supposedly asymptomatic patients. That will include reviewing chest x-rays and patients’ clinical course, then identifying a method to determine who’s positive independent of the test result. The gold standard is either another test known to be 100 percent, she says, or a clinical scenario. “And we don’t have either.” She points to a June 5 New England Journal of Medicine “Perspective” piece (Woloshin S, et al. doi:10.1056/NEJMp2015897) that explores the topic in depth—and includes data out of China that indicates an assay clinical sensitivity of 70 percent. “That’s appalling,” she says. “I’m hoping ours is better than that. But we don’t have any idea.”

Another key study—when there’s time—would be one looking at recuperative antibodies. “That absolutely needs to happen,” she says. Did patients who tested negative produce antibodies? “I would love to know that.” And how long do very sick patients shed the virus? “We don’t know that either.”

She doesn’t anticipate a need for additional prognostic tests down the road, but the fact that COVID-19 patients are hypercoagulable seems like a crucial clue. “We need to know who we should be following and when we should act. When do we look for coagulopathy?” As protocols emerge, she anticipates relying on straightforward lab tests such as D-dimer and C-reactive protein; there will likely be a role for markers of cytokines as well as coagulopathy, she predicts.

She’s keeping an eye on innovative work being done by clinicians who’ve seen vast numbers of COVID-19 patients, including those in New York City. “But it hasn’t hit the press,” she says, “because who has time to write about this stuff when you’re taking care of patients?” She and her colleagues did evaluate the clinical performance of three molecular assays in symptomatic patients during the initial height of the pandemic (Cradic K, et al. Am J Clin Pathol. 2020;154[2]:201–207), “but putting it together was a real struggle.”

Absent a robust literature, Dr. Fuhrman has turned to (among other sources) a podcast, “This Week in Virology,” which drops twice a week and is hosted by PhD virologists. Particularly interesting, she says, are the conversations with contributor Daniel Griffin, MD, PhD, of Columbia University Medical Center. “He’s got some great information about what they’re seeing clinically,” she says, adding that she and an ID colleague listen and discuss content regularly. “It’s phenomenal,” she says. “We’re just eating it up.”

Dr. Fuhrman also oversees antibody testing (“I’m all things COVID,” she jokes) and is working with medical staff to figure out how to use it to add value. The test is not useful for diagnosis, obviously, but it might augment information on confusing and complicated cases.

The larger use for antibody testing remains in the public health setting, of course, but it’s still a foggy area for the public. “And the clinical use is even confusing to physicians,” Dr. Fuhrman says. Indeed, she had just worked with the medical director of her clinical chemistry lab to write an educational piece on serology for their physicians. “Again,” she says matter-of-factly.

Dr. Sossaman also reports a sense of déjà vu in his conversations with clinicians. He’s frequently asked about discrepancies between test results, or between results and clinical sensitivities. Or, colleagues might ask about using antibody testing preoperatively. “We continually seem to answer the same questions for people,” he says, with no trace of impatience. “There’s so much information coming at people.” That’s turned the lab into a de facto town crier.

When one vendor told him they were starting to see reports of higher positivity rates in some areas, for instance, it was a possible indication that the curve wasn’t as flat as some had presumed it to be. “So I’ll pass that message along to my clinical colleagues and let them know what’s going on.” Which, of course, will spur more questions. “But that’s our role,” Dr. Sossaman says. “We’re sort of a central clearinghouse for information.”

That’s especially valuable, he says, when information is confusing. “We tell our colleagues, This is what we know—let’s decide together what to do about it. We’re very upfront about what we know, what we don’t know, and what we’ve seen in the literature.”

In some ways, the lack of information has been freeing, Dr. Sossaman says. “We’ve made a little bit of a transition in our way of thinking. Rather than being the deliberate voice, which the lab always is, we’re the proactive voice.”

That’s due in large part to that Grand Canyon-sized lack of data. Much as he’d like to talk about the test performance in the usual terms, he simply can’t. Hence his pivot. Instead of responding Yes, but . . . , Dr. Sossaman and his lab colleagues are pulling a page from improv and learning to respond, Yes, and. . . .

Is a colleague asking about saliva testing? Sure, let’s look at it. Swab and saline? Let’s go ahead and look at it. Do more testing? Let’s see what we can do. “Whatever is put in front of us,” Dr. Sossaman says.

The natural inclination in the lab, driven as it is by process and procedures and heavy regulation, is to safely pump the breaks, so to speak: Where’s the data? What’s the need? Can we do that? Do we have the staffing? How much is it going to cost?

Good questions, all—but not at all productive in a pandemic, he says. “That kind of thinking would have gotten in our way. So we quickly changed our stance to, How can we make it happen? And how can it be as fast as possible?”

The pandemic hasn’t changed everything, of course. “We’re still scientists,” Dr. Sossaman says. “We’re still realistic.” But waiting for the perfect test, at least for now, is off the table. Instead, they’re bringing a new shade of meaning to reflex testing. “Our answer is reflexively, Yes. And then we figure out a way to make it happen.”

One thing that hasn’t happened, much to the dismay of many in the lab, is a more coherent and cogent federal response to testing.

Those who’ve spoken to CAP TODAY, on the record and off, are quick and careful to say they’re not talking about politics. But concerns about politicization weigh heavily over testing, they say, as does the fact that individual states are charged with figuring out how to manage testing, sometimes in competition with one another. Policy and government have become almost unspoken pre- and postanalytical variables, though they have nothing to do with testing itself.

“And yet it’s all a lab problem,” Dr. Nolte says.

Eyeing the “intersection of public health, politics, panic, regulation, fear of the unknown, and media hype,” Dr. Nolte sees a pileup. “This became a political event rather than a public health event. That’s where this really went bad,” he says.

The lack of a national health system in the United States has added to testing woes, Dr. Fuhrman says. The dispersion of individual hospitals and health systems spread across 50 states was a liability against a virus that doesn’t respect man-made borders. And any wider response “has been appallingly disorganized,” she says.

That includes reporting, which Dr. Fuhrman calls a nightmare. Labs had to submit reports to three different agencies—state, county, and federal—all of which use different forms and require different information. “That’s inexcusable.”

She called on groups such as the CAP, CLSI, and AMP to lobby for changes to “stop the madness,” as she puts it. “You want us to do the tests, we can do it. But the amount of time we’re spending just writing software because they cannot get their act together—that’s just not right.”

Her comments came weeks before HHS issued, on July 10, new requirements for reporting COVID-19, including for laboratories (https://j.mp/HHS-reportingfaq). Responding to that change, she voiced a concern that many shared—that the new requirements bypassed the Centers for Disease Control and Prevention.

“To use precious lab resources appropriately, we should have a streamlined reporting mechanism to a single entity, presumably the state, as they have generalized authority and jurisdiction over public health,” she wrote in an email. “The federal government should obtain the data from the states. We shouldn’t be cutting the states and CDC out of the data flow nor should we have to provide two, three, or four data reports.”

The change involves a technical challenge as well, she wrote. “Many of the new required elements of reporting require information from patients that we do not normally gather nor do we have discrete data fields in our IT systems to record the data.”

The aforementioned pressures on labs to justify their use of, and requests for, supplies and reagents may point to another issue, says Dr. Sossaman, whose vendors ask him for a strict accounting of how he uses resources. “They say, We can’t just send you this. Are you really running these tests?” He suspects it reflects the tremendous pressure vendors are under to justify their own actions.

“It’s been very confusing from a national perspective,” he adds. He hears conflicting messages from vendors about how the federal government is maneuvering reagents and supplies “to affected areas or snapping them up and redirecting them.” It’s a tricky situation, he says, because there’s no transparency around the process. The only thing that is clear, he says, “is that there’s absolutely no national testing strategy. It really shows.

“We need one,” Dr. Sossaman continues, in no uncertain terms. Leaving the states to fend for themselves isn’t working, in his view. Encouraging competition between local and regional entities has led to imbalances in the supply chain, and it’s been left to vendors to rebalance. Large systems like Ochsner have an advantage, he notes, and disparities in health care delivery will only increase.

Dr. Fuhrman concurs that vendors are following the directives of the government, and that the process remains shrouded in mystery. “I don’t know their secret sauce,” she says, adding that she’s been told one vendor has been lobbied by a congressional delegation. “So if you don’t have your governor or senator on the case, forget it,” she jokes. She, like others, notes that there’s been unprecedented cooperation between labs over the course of the pandemic. At the same time, she can’t starve her own system, either. “It’s been really, really hard,” she says.

A national strategy would make it easier for sites with unused capacity to support labs that are getting slammed, Dr. Sossaman suggests. It would be a huge step to have a national database—“almost like a dashboard”—to monitor unused capacity and allow, say, Texas, to send testing to New York. “How does that not make sense?” he asks. “Right now, everything is so fractured.” It would be fairly easy to put together such a scheme, he says, but it would require federal authority to pull it all together.

Dr. Nolte pulls no punches when he considers the national scene. Current use of testing resources “isn’t the best utilization. We know it’s not sustainable.”

“I’m sorry, but we have had a total failure in leadership at the federal government level,” he adds. “I think that if the current Administration realized this was a significant problem, and that they need to get the best and brightest people working on it, and to step out of the way, things might have gone differently. It’s been a mess. Unfortunately, there are lives at stake here. Lots of lives.”

He speaks highly of medical leaders such as Deborah Birx, MD, and Anthony Fauci, MD, but they don’t represent the clinical lab practice—a frustrating situation that he sees being played out on the local levels as well. “We can’t get a seat at the table,” Dr. Nolte laments.

The inability to amplify the lab voice has also bothered Dr. Thomas Williams. Nebraska, rarely a state to draw attention to itself, has maintained its unassuming profile during the pandemic as well, managing to stay out of headlines and dealing with numbers that produce neither scary spikes on graphs nor maps colored red. But it, too, has been affected by the lack of a national test strategy, and along with others, Dr. Williams has felt the frustration of having non-lab voices calling the shots. “In the course of surveying the state, I talked to a number of laboratory people and they were enormously frustrated, just like the reps were. They couldn’t blame the reps. The decisions were made above them.”

That’s important for two reasons, he says. One is on the technical level, obviously. “The other is the Realityville test of what’s out there.” As he listened to physicians on the federal level—whom he admires—talk about the ability for labs everywhere to perform COVID-19 testing early on, and the reports of reagents being widely distributed, he knew his colleagues in the state had a different story to tell. “I’m looking at Nebraska, and it’s sucking canal water.

“From my perspective, they should listen more to what is really happening out there,” Dr. Williams continues. “They were very adamant that we were swimming in reagents, and I can tell you that outside of Omaha, nobody—not one lab—had reagents. And that’s a lot of labs. I practically threw something at the TV on a couple of different evenings” when he heard nonphysician leaders proclaiming their success in distributing reagents. “That made me very angry.”

For all the changes wrought by COVID-19, some basics in the laboratory have changed not one bit.

Dr. Sossaman has been able to work so proactively with his clinical colleagues because the lab had already had deep bonds with them. “It’s been interesting to see how those relationships really crystallized during this period of time,” he says.

It’s a point Dr. Williams returns to as well. His years of working with public health professionals, other professional associations, and vendors, as well as his time working in government, were invaluable as he helped prepare communities and counties in Nebraska for SARS-CoV-2. “There isn’t going to be cavalry coming in to take care of it for you,” he says.

His own survey of test availability turned out to be far more accurate than the map distributed by the federal government. “I knew where every assay analyzer was,” Dr. Williams says. “They missed a whole bunch of them. They said, ‘We have a map of where all the tests are in your state.’” Dr. Williams’s response is swift: “No, you don’t. You have a map of where some of the tests can be done.

“I don’t know where they got their data,” he says. But he knows where he got his—by reaching out directly to colleagues, many of whom he already knew.

Dr. Fuhrman sees another steady aspect in the midst of otherwise relentless change. The laboratory has “always knocked it out of the park,” she says. But now the stands are filled with people and the game is being broadcast. “We step up to the plate all the time,” she says. “I don’t know that it’s ever been so public. We’ve always made a huge difference, but it wasn’t as noticeable.”

The camaraderie and can-do response from her laboratory colleagues has buoyed her. “Everyone has just dug in, and we’re working all the time, weekdays, weekends, round the clock, and everyone is doing whatever they can to help patients. It’s phenomenal. It’s been a defining moment for the laboratory.”

Oddly enough, it’s one she almost missed. “I was originally planning on retiring in January,” she says.

Karen Titus is CAP TODAY contributing editor and co-managing editor.