A lab world embroiled in pandemic

Kaiser Washington was running 200 to 300 tests daily in early April, for the most part limiting testing to patients with symptoms of COVID-19. Dr. Greene acknowledges that waiting to test asymptomatic but clearly exposed patients is controversial. “Should we be trying to adopt more universal screening?” she asks. “Or should we be saving resources? I don’t know. It’s a very interesting ethical problem. We know we have a limited amount of swabs and transport media. And then there’s some amount of bottleneck in the analytical capabilities.”

In Atlanta, Dr. Rogers, who is also adjunct professor of pathology and pediatrics, Emory University School of Medicine, says she faced tremendous pressure from colleagues to have an in-house test. “We weren’t going to bring up our own LDT. We have a great molecular diagnostics lab, but it’s small and does a large volume of clinical testing.” In the meantime, she sent samples to a commercial lab, which went from a two- to three-day turnaround to what she calls an I-don’t-know-what TAT. Finally she was able to send samples to another institution in town, which gave her 24-hour TAT—and some much-needed if short-lived breathing room. “People were relaxing a little bit at that point.” Dr. Rogers spoke to CAP TODAY on April 7, the day testing was brought in-house. “But soon the doctors are back, saying, ‘We need more testing than what we are getting.’”

“The surgeons are anxious,” she says—“understandably so.” To conserve testing for symptomatic patients, the surgical services were given an allotment of collection kits to test asymptomatic patients before surgery. Then a surgical director thought to ask: If we use them at this pace, we’re going to be out in April—can we have more?

“It has been tough to comprehend that raw materials to make kits and reagents aren’t available,” she says.

One surgeon asked her, “Bev, what can I do to make this happen?” she says. “And I said, ‘Not a thing. Allocation is allocation, and children’s hospitals aren’t high on the list to get test kits.’”

While necessity is the mother of invention, a pandemic can be the parent of possibility. “We’ve seen a lot of great things,” says Dr. Sundin. Early assays were able to go live quickly, with manufacturers then “going back to update their EUA to allow more sources, or to validate saline—one vendor is allowing you to use pool chlorine to clean their hardware after a run. So we’re all getting creative about what’s going to affect test performance.” (Dr. Rogers reports a lab colleague who was trying to validate urethral swabs.)

Dr. Sundin heaps praise on vendors in the midst of the madness. “I’m so impressed by the collaboration between diagnostic companies. I’ve never seen anything like it.” No one is demanding she use their instrument solely or commit to volume. “We’ve been really open with them that they’re supporting a portion of our volume and not all of it. The only thing they’ve asked for is standing POs,” which she can adjust in ensuing months. It boosts confidence on both sides, she says: Vendors know their assay will be used, and she feels more sure-footed of her future supply chain. “We also don’t want to hoard supplies,” she says.

Your first time in a lab?
At Kaiser Washington, deciding who would be tested fell to leaders “way above me,” Dr. Greene says, which she suspects has been the case throughout the country. “This is not a lab director decision.”

That’s led to other novel scenes, she suggests. “This is a time where everybody thinks they know how to run the lab,” she says with a laugh. Indeed, it bears a resemblance to the exuberant lead-up to the stock market crash of 2008, when everyone seemed to be a whiz at investing and mutual fund managers were media darlings. “I’m not saying I should be the one who decides who gets tested, but in many cases, the lab and the people with lab expertise are probably being consulted less than they should be.”

She casts her gaze cross country. Has a laboratory expert been named to prominent task forces? Spoken at White House press conferences? She answers her own questions. “There has not.”

“There have been very smart physicians who are part of our federal government response,” Dr. Greene continues. “But none of them have been laboratory people to explain what’s going on.”

Dr. Rogers saw a similar problem locally. “People are so anxious in this environment that well-meaning conversations about capacity occur among administrators and physicians outside the lab with other organizations. This happened with a promise to help made by someone at another institution, but when I called the lab director myself, he said, ‘Bev, I wish we could do your testing, but we don’t have any capacity.’ Multitudes of suggestions come into the lab about how to increase our lab’s testing capability. We have to investigate and bring things back to reality about what is and isn’t possible.”

Dr. Sundin has been encouraged as she watches lab testing become part of the conversation. Sentara’s senior leaders have walked through the labs on a handful of tours (as have local news organizations). “We actually had the COO ask, ‘What do you all do on a normal day?’” The answer—virology, genetics, and oncology-related testing for the entire system—may not have previously been apparent, she says. She’s also used the opportunity to explain sensitivity and specificity on the analytic side versus the clinical side. “Now that they’re in here they understand that we are central—no more for COVID than anything else—and they actually get it. And they’ve all said, This is your time to shine.”

“I would actually call it a silver lining of this whole process,” Dr. Sundin adds.

Dr. Rogers also finds herself explaining lab medicine to other colleagues. In response to the nonstop questions she was getting, in fact, she put together what she calls tip sheets—sort of a field guide to COVID testing basics, including major vendors. She was spurred to do this by a seemingly small incident: As she sat in on endless rounds of meetings, she realized leaders were trying to make decisions about tests whose names they couldn’t pronounce.

The tip sheets, simple and low-tech, helped with that and more. “People felt better simply because they had facts,” Dr. Rogers says. She followed this with a one-page brief on the assay Children’s started using—sensitivity, specificity, how it’s validated, how it’s done. She even included pictures of the instrument. “You know what? People became calmer.”

Everyone in
As Waugh watches the surge beds fill up, he marvels at the response from colleagues. “Exceptional—just exceptional—work has been done by our entire team. I have never encountered a situation where people step up, and cross over into other areas and backfill, and continue to come to work. I’ve just never, ever seen that kind of thing happen before.” This included those from the transplant immunology lab who began working in the microbiology lab. “They helped extend our staff, who at that point had been working nearly 28 days straight.”

He also commends the work done by the transfusion medicine division head. “I was initially concerned about our blood supply,” given that collection sites closed under stay-at-home orders. The supply has been skillfully managed, he says, and the division has worked to harvest plasma from convalescing patients who tested positive. He applauds the work of the pathology informatics group as well, who brought order to the intricate daily testing reports, surge beds, and new order codes.

In trying to keep laboratory personnel working, members of the lab outreach team—no longer engaged with private offices that had closed—were deployed to the lab customer service center, Waugh says. “We were getting hammered with telephone calls from people who wanted to know, Where is my result?” That was especially difficult to untangle early on, when samples were being sent to five different locations: in-house, the state public health lab, and a reference lab that referred it in turn to another reference lab, which then passed it along to yet another site. “It took a lot of detective work,” Waugh says.

Sometimes the samples were much closer, but untested. “At one point we had a queue of 900 health care [worker] samples in our refrigerator waiting to be tested because we did not have testing supplies.” The alternative? Send them to a commercial lab and wait two weeks.

Ultimately all those were tested. “There was a lot of heavy lifting by our staff,” Waugh says. “I’m extraordinarily grateful.”

Dr. Sundin, too, lauds her colleagues inside and outside the lab. “I have a team I can’t thank enough,” says Dr. Sundin. “But I’m also seeing that with my other colleagues—our teams are all stepping up and managing the pandemic from the front line. I think that is really true for most lab professionals.”

Henry Ford has its own LDT but also turned to four other EUA procedures. “We bounce back and forth between different ones, depending on when the consumable supplies are coming in,” Waugh explains. The replication—of workstations, training, IT, supply and delivery orders, and payment—has added levels of complexity. It also was an opportunity for others to shine, he notes. He says he’s “exceptionally proud” of colleagues who work in supply chain and in finance, “who helped speed things along that we needed desperately. It didn’t matter the hour of the day or the day of the week.

“I said to people, ‘Every day is Monday. That’s just the way it’s going to be. Pandemics do not take time off. Pandemics do not have weekends or holidays.’”

Dr. Greene applauds the work of colleagues throughout her state. “We’ve done a really good job getting lab tests out, which is partly the work of Alex Greninger. We aren’t actually being recognized for the speed at which we’re doing this, and for the positive predictive value of the test.” By late April, Washington, along with California and Oregon, had begun shipping ventilators to East Coast hot spots, reported The New York Times. Until mid-March, Washington had the highest number of confirmed cases in the country.

Says Dr. Greene, “We’ve been able to calm down a little because we’ve seen what we’re doing is working.” Early on, one of her colleagues at UW said he wanted Washington to be the South Korea, so to speak, of the United States. “I thought that was a great goal,” Dr. Greene says. “That’s not to say we’re not having an increase in cases, but it is to say our strategy has mitigated risk. And that includes testing people.”

Facts versus wishful thinking
The pandemic has pushed the importance of lab testing into the national conversation. It hasn’t always been a pretty sight.

The challenges of testing have crashed head-on with perceptions at a fundamental level, says Dr. Rogers. “We live in America. We have our comforts; we have our freedoms. We have every test we want, when we want, how much we want. And that’s just not life right now,” she says.

“Part of the issue that we’re seeing with the national news is setting up an expectation that anybody can be tested before we were really capable,” Dr. Sundin acknowledges. She sighs heavily.

Those promises popped up around the time labs were pushing ahead with their LDTs. “Millions and millions—everybody’s going to get tested,” echoes Waugh. “And the reality is no.” The backlog was at least three weeks, he says, when leaders were making those promises.

That optimism trickled down to clinicians. “We’re all being cautious,” Dr. Sundin says, “and our physicians want more data rather than less. But we have to manage their expectations about what a proper turnaround time looks like. Most of these tests are not point-of-care, even though they’re being marketed as such.” That has translated into national news reports saying that POC tests can provide results in five minutes. “We can’t fulfill that promise,” she says. That was also a frustration with the drive-through testing sites—not testing sites at all but rather collection sites. “But the local and national news presented this as ‘testing’ and talked about the limited supply of ‘testing kits.’ There was a lot of confusion.”

That confusion was being perpetuated from a high level outside the lab, Dr. Sundin says. “It almost sets the lab up not to meet the expectation that’s been given.”

Dr. Rogers marvels at the leaders who are talking about testing. “And so inaccurately,” she adds.

That made it more difficult to manage her colleagues’ expectations. “When we didn’t have this test in-house, there was such anxiety. Because we’re a lab that delivers. And we couldn’t deliver. It’s the first time that anything has been this extreme, where I said, Sorry, I can’t do it.” She did what she could to meet the needs but it often wasn’t enough. “I felt helpless and like I was personally failing.”

“Part of my job as a laboratory medical director is just to be an anxiety sink,” she continues. That’s why her fact sheets worked so well, she says—they tamped down the anxiety colleagues felt when everything felt chaotic and in constant flux. “I think just giving them facts is useful,” she says.

Of course, she adds, “To some degree, that’s all I could do.”

But it’s valuable, she says. “It’s so important to give a clear message at a time of crisis and chaos. If I could share one thing with the federal government, it’s that clarity of message, and basing every comment on fact rather than emotion, is extremely important in times of crisis.”

The conversation continued when the first antibody kits came on the scene, Waugh says. And it persists as governors publicly discuss the merits and meaning of antibody testing. Such scenes, which at the start of 2020 would have seemed astonishing if not downright disorienting, are now the norm. Once again, those with no laboratory experience are placing enormous demands on it. Will antibody tests be used to reopen economies? Will there be similarities to HIV testing, when patients who are positive but have undetectable viral loads are unable to transmit the virus? “We’ve always used lab testing to change behaviors,” Dr. Greene says, “but this is on a global scale. It’s unprecedented.”

At the same time, those who worried about the slow rollouts of LDTs are simultaneously asking the pendulum not to swing too far in the other direction with antibody testing. “My fear,” says Dr. Greene, “is that things are oscillating to the other side. There is a lack of regulation that’s a little bit unnerving.” Then again: “We are in a high state of emergency.”

What’s ahead?
In between managing diagnostic testing and antibody testing, labs are also considering the next wave of the pandemic, which many deem inevitable. Preparations might be different, or they may not be.

A member of Children’s leadership asked Dr. Rogers if anything could have been done differently. She responded that it’s likely nothing would have made a difference, because of the scarcity of raw materials. “And pediatrics is not where the greatest problems are.” (Even so, the virus looms large at Children’s. “While we are the least affected by all this, it feels like we’re extremely affected because COVID is what we do all day,” says Dr. Rogers. On the day she spoke with CAP TODAY, she had five scheduled COVID meetings, with additional COVID meetings squeezed in between.)

She told him she could plead with an adult hospital to take on her admittedly low volume of cases—“but that means there’s an adult they can’t test. And they’re sending tests out themselves.”

Dr. Sundin, who oversees molecular diagnostics as well as serology (“It’s not like I’ll get past RNA testing of COVID and then get to hand it off,” she says with a laugh), had sourced rapid IgG/IgM kits. “We’re not exactly sure where the testing will move,” she says, “but we want to have the option to move in that direction.” She was also fielding questions about employee health screening, as well as hearing from vendors that plan to offer serological boxes with an EUA. “So we will probably transition quickly to an automated method for that—hopefully on a chemistry line, which I could hand off to the chemistry clinical specialist.” As with the RNA testing, she’ll likely diversify the supply chain.

She sees the need for more data from serological assays to understand how they’ll pair with both PCR assays and patient management. “I’ve seen the data on serological conversion for IgM; with IgG, we need more data to know when they’re going to convert, and is it specific to COVID versus other coronaviruses.” In addition to such data, she hopes the WHO or CDC will suggest an algorithm that combines serological and PCR testing. Without that, Dr. Sundin predicts widespread confusion as physicians try to interpret both results. “We want to make sure we’re giving guideline-driven care despite the fact that this is moving fast.”

Large-scale data will be hard to get, and no one has the luxury of time. But Dr. Sundin says her institution will be able to perform smaller studies using their own samples—“discarded serum from patients who we know are positive or negative, and actually challenge the assay.”

Looking back and looking forward, Dr. Sundin says she’s hard-pressed to figure out if the lab should have reacted differently, or will in the future. Since it’s based in the hospital, there’s little storage space to accommodate larger supply stocks. Off-site storage might be an option, but that would lead to worries about expiration dates and test performance, given that a warehouse is not temperature controlled.

The larger issue is that, “although I would love to be prepared with enough reagent, we don’t know what testing is going to be required” in a future pandemic. “Is it going to be an antibody test? A chemistry test? A PCR test?”

Dr. Rogers agrees. “You don’t know what test you might need. Storage space is limited. And specimen collection kits don’t last forever.” Ironically, she says, clinicians might actually use fewer collection kits in the future, perhaps having been spooked by the lack of supplies this go-round.

The changes she would like to see would be ones outside the lab. “One thing that would have gone much better is if we had had testing capability earlier. I think the U.S. let down its guard. I hope this will be a reminder about scaling up fast to do the testing, define the protocols, et cetera. That’s really the area that let the country down. And I don’t think it’s the manufacturers at all.”

“I would hope,” Dr. Rogers continues, “that this is an opportunity for us as a nation to learn something. If you don’t learn from a crisis, then it’s wasted. And I would hope that those who can effect national changes will do so, so we can be prepared when, not if, this hits again.”

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