Flu mounts COVID’s bustling stage

She recalls a conversation with someone who asked her, If we gave your company a couple million dollars, could you make a million tests a day? “Well, we’d have to build a whole new building and new production lines. And we can’t get raw materials. Everybody is trying their best, but you can’t do the impossible.”

Everyone is scuffling up the same mountain. The diagnostics companies share suppliers, Dr. Ginocchio explains. Even if manufacturers can lock in backup suppliers, those suppliers “may not be capable of making it in the same vast amounts as your primary supplier.” And it may not be reasonable, business-wise, for smaller suppliers to gear up for a massive demand that could vanish in a year.

Companies have been through the same economic challenges as everyone else, Waugh says, including different degrees of lockdowns in various states. They’ve also had to ensure worker safety, such as reconfiguring work spaces/production lines and perhaps offering COVID-19 testing. These are solvable problems, but they’ve “introduced some level of delay and caution,” Waugh says.

And while companies are working quickly to develop SARS-CoV-2/flu tests, Waugh says, they won’t scale up for mass production unless they have a very high level of confidence that they’re going to get EUA approvals. Otherwise, if the FDA requires change, “now they’ve made too many of the wrong product.”

There’s nothing new about the process, and most companies are savvy about how it works. But it is an added step, made more fraught by the pandemic.

Moving too quickly has its own perils, Dr. Ginocchio says, citing the FDA bulletins with alerts that a test is not performing correctly or will have its EUA revoked. “You can’t blame the manufacturer,” she says. “Everybody’s doing their best, quickly.”

She extends that praise to the FDA, which, she says, “has been doing an amazing job. I cannot give them enough credit. And I feel bad, because they’re always going to get blamed. They’re working 24/7 to get tests approved, constantly upgrading guidelines and protocols.” She anticipates fewer roadblocks in obtaining EUAs, “simply because the FDA has worked out its own kinks.”

All of this will doubtless make for a series of interesting case studies at Harvard Business School one day. But labs don’t have the luxury of time.

The manufacturer of one multiplex test Dr. Pritt is interested in says it hopes to have it available by October. “But none of that is guaranteed,” she says. And even if the test is ready on time, “we don’t know for sure that they’ll have enough to give us.”

Waugh isn’t worrying about delays, but he and others note that EUAs were taking longer to come through. “Initially the FDA had a very, very open policy on emergency use authorization,” Waugh recalls. EUA wasn’t spoken quite like a four-letter word, but many labs came close as they dealt with the fallout. “Once they opened the door we frankly had a lot of bad product that came into the U.S. and other parts of the world.

“The FDA has seen that,” he continues. “They know it, and they’ve heard from others, and there have been publications that have cautioned about products that have had poor performance characteristics or that were minimally tested, and now they are taking a more studied look at these.” He sits in on a weekly FDA call where these matters are discussed. His colleagues at diagnostic companies are a little surprised by the slower pace, he says, but no one is feeling a sense of urgency.

Ordering physicians may feel otherwise, especially with “flu season creeping closer to us all the time,” Waugh says. “Everybody would like the largest multiplex system that will give them the fastest results. Everybody wants to be in the express lane.”

But labs need to remain agnostic, says Waugh, given that they’ll be leveraging multiple systems with multiple supply streams of varying reliability. “We don’t want to steer them, or let them steer themselves, toward a specific test. We have worldwide constraints for these products, and the ones that are the most comprehensive and the quickest are the ones in heaviest demand.” That also creates internal constraints for large systems like Henry Ford that have multiple emergency departments and urgent care areas.

Demands for COVID-19 testing aren’t slowing down, either. “Everybody wants to be tested,” Schofield says. “For free. Yesterday.”

Much of the demand he’s seeing is coming from schools, corporations, and surrounding states. One asked about testing three counties’ worth of nursing homes, totaling 700 patients a day. “From a business standpoint I’d love to be able to do that,” he says. “From a being-able-to-deliver-the-goods standpoint, I’m very worried.”

Schools are contacting him about testing students. Each has its own algorithm (“It’s going to be fascinating to see what works and what doesn’t,” he says), each with a different demand for test kits, TATs, etc.

Tempting as those offers are, Schofield can’t lose sight of others in need of testing: the 1,400 MaineHealth patients a day who are symptomatic or need preprocedure/presurgical testing. “I can’t tell them to go away,” he says.

It’s possible two other approaches—pooling and antigen testing—could help ease pressure. Quest and LabCorp have EUA for pooling, Waugh says, and other organizations are likely to take their case to the FDA for consideration as well. “Just to have that in their back pocket if they need it.”

Pooling could help with lengthy TATs, though “it’s not a first option for us,” he says. In areas with low prevalence—maybe three or four percent—“pooling can extend the supplies you do have.” But it’s not an everyone-into-the-pool scenario. In addition to well-known concerns about loss of sensitivity, pooling triggers a separate set of sample management steps. And when prevalence starts to creep up, it becomes less attractive.

Antigen testing could fit into the flu picture if it can be done on automated systems. “Because then it becomes sort of the parallel of the antibody testing environment,” Waugh says, “where you’re leveraging chemistry automated analyzers able to handle large numbers of samples.” That could work for testing larger populations of people, such as schools, universities, businesses, and sports teams.

Those tests were still in development when Waugh spoke with CAP TODAY in mid-August, though he expects them to be available by the start of flu season. “And those will be another tool in the toolbox for some of these mass screenings.”

The tests may run into the NP swab supply problems that have dogged the pandemic response from the start, though, which has some eyeing tests that use saliva samples.

The same late-August day Dr. Pritt spoke with CAP TODAY, Illinois’ governor was hailing a University of Illinois-developed saliva-based test as a game-changer that would help students return safely to campus. When such tests make a media splash, says Dr. Pritt, “All of our colleagues are calling us: When are we going to get this?

“And then you have to educate them that it’s not that simple, and it may not be a good test for us, and here’s why. It’s a little frustrating,” she says. “Every time there’s a news headline, then things get a little blown out of proportion.” Though the saliva-based tests are easier for patients, “it hasn’t made testing any easier,” Dr. Pritt says. It’s still a three-hour test. And even if a new test is inexpensive, running it still requires staff and overhead. “Labs are still going to charge the normal price for it.”

Nor are samples foolproof. “You just don’t know from person to person what the full utility of a saliva sample is going to be,” Waugh says. “That’s why nasopharyngeal has stayed in first place as a sample of choice.”

Dr. Ginocchio has her qualms about antigen testing in general. In what situations do you trust a negative test, she asks. Likewise, repeat tests increase the chances of catching positives. But is it practical? Dr. Ginocchio has her doubts. “People won’t understand that: I had a COVID test, and it was negative—I’m fine. And to have people return two and four days later for repeat tests, I think is going to be quite difficult.”

There are no good markers for beliefs or behaviors, with their sometimes corrosive, sometimes ameliorating effects.

At Notre Dame, Touchdown Jesus did not appear to help suppress the virus, and the school—along with others since—had to shift, at least temporarily, to remote instruction after early COVID-19 outbreaks. And at the University of Illinois, the comprehensive and well-regarded testing plan took a hit when students continued their risky behavior even after testing positive; some tried to circumvent the app designed to vouch for negative results, reported The New York Times in September.

Human actions have become de facto pre- and post-behavior variables. “We’re never going to be able to meet the demands of people who want to get tested every day,” Dr. Pritt says. “We’re not going to have enough supplies for that. We hope we have enough to test all of our sick people and at-risk people. But it’s a limited resource, so we need to protect it. And to do so we need help from the public to prevent infections that are easily preventable.”

“I’ve had a lot of conversations about testing, limitations of testing, different approaches—should we use pooled specimen testing, should we use antigen testing,” she continues, running through the same questions labs have always tried to answer. “But one thing I always come back to is if everyone wore masks and socially distanced, the COVID outbreak would go away. We have very good data now that wearing masks prevents transmission. We know they’re effective. We need to continue that message of how important it is to wear a mask.”

Dr. Ginocchio puts it even more bluntly. “We don’t want to waste testing.”

The tail end of the last flu season offers encouraging information about how thoughtful behavior might affect the upcoming one.

Looking back, Waugh says, “When we went into COVID season, we had been on a seasonal flu protocol.” As SARS-CoV-2 testing got underway, “Our initial position in the February/early March time frame was let’s rule out flu first,” Waugh recalls. For those who tested negative for flu A/B but were symptomatic, SARS-CoV-2 testing was the next step.

As March began its free fall, providers decided it made more sense to look for SARS-CoV-2 infections first. “We essentially declared an end to flu season when we started seeing more flu B than flu A,” he says.

Dr. Ginocchio cites emerging data that tell “a fascinating story” regarding that time. Respiratory virus testing positivity rates can be as high as 60 to 65 percent in the peak winter months, she says, with flu between 20 to 35 percent of the positives. Respiratory viruses still circulate in the summer months, but overall positivity rates drop to about 30 to 35 percent.

At the start of last March, Dr. Ginocchio says, respiratory virus positivity rates were at their expected winter levels, with the typical, gradual decline evidently underway.

Then COVID-19 hijacked the health care system, and quarantines, social distancing, and masking took hold. “By the end of May,” Dr. Ginocchio says, “our detection rate for all respiratory viruses was down to less than 10 percent, which is incredibly low. We don’t even see that in the summer.”

It’s not that the viruses took a hike. “They’re always there,” she says. “It’s just that transmissibility went away. You should wash your hands.”

Dr. Ginocchio has her own version of phase one, two, three, etc. Unlike the governors who mark these as steps for reopening their states, she uses her version to get a handle on coinfections.

Phase one, in this scheme, describes the emergence of COVID-19 in the months of March and April. SARS-CoV-2 was low in most areas, but other viruses were circulating at their normal levels for this time of year. Coinfection studies at the time saw 20 to 25 percent of non-SARS-CoV-2 viruses circulating among patients with and without COVID-19 infections.

Phase two describes the massive influx of COVID-19 disease, as seen in New York in early spring. “The number of other viruses coinfecting COVID-positive and COVID-negative patients was two to three percent—really, really low,” Dr. Ginocchio says.

“Testing may have been biased at this time with a focus just on COVID-19, but also quarantine, lockdown, better hygiene played a major role. If you do not transmit COVID-19, you do not transmit other respiratory viruses.” She saw a marked decrease in gastrointestinal viruses also during this time.

Phase three covers more recent history, where COVID-19 positivity rates are trending up as reopenings expand. Each part of the country, and its inhabitants’ behavior, varies. “People are tired of being on lockdown,” Dr. Ginocchio says. “So we’re starting to see the reemergence of other viruses also, but less than normal.”

She expected clues to be seen by early October with the start of the rhinovirus season. That could be a good indicator, she says, of what might lie ahead. “And then RSV, which usually starts to come in drips and drabs around October/November, and then really goes up in December and January.”

“Usually” being the key word. This year, such norms might be as bankable as a Confederate dollar.

“We really don’t know,” Dr. Ginocchio concedes. For the traditional viruses, “I think the numbers won’t be what we normally expect, because people are being respectful of social distancing,” though, as she and others point out, this is partly geographic-dependent.

Waugh says that people “who want to be safe” have accepted social distancing and masks, and are avoiding oversized gatherings. “Of course, you have contrarians who go the other way,” he says.

And for himself? “I’m careful. I think about which way I’m pointed,” he laughs, “and who’s pointed at me.”

Australia, with its jump-start on winter, offers a ray of hope for the season ahead. Its influenza rates have been historically low, Dr. Pritt says, likely the result of behaviors that took aim at SARS-CoV-2 transmission. The same thing could happen in the United States, she says, leaning heavily on the word “if”—if people continue/start to mask, distance socially, and so on.

It’s not a given. “We have to prepare for the fact that people might be so burnt out, they might stop all those helpful measures,” she says. “Then we could see a really steep rise in cases.”

Dr. Pritt worries about what that could mean not only for testing, but for her already stretched-thin staff, who also are vulnerable to flu and COVID-19. It’s a headache that bedevils Schofield, too. “Adequate personnel is my number two worry, behind supply chain issues,” he says.

With a COVID-19 vaccine in the works but likely unavailable for the foreseeable future, physicians are emphasizing the importance of the flu vaccine this year. Some providers have mandated vaccinations; Mayo is using an opt-out approach.

Such approaches could boost vaccinations. On the other hand, with more employees now working from home, office sites may not offer the easy, widespread flu shot delivery they have in the past. “Good point,” says Dr. Pritt. Perhaps there will be drive-through vaccines at clinics, similar to the drive-through collection sites for COVID-19, she says.

The human behavior wildcard, mixed with vaccine skepticism in general, could also affect vaccination rates. “Although if the pandemic hasn’t motivated people to get a flu vaccine,” Schofield says, “I don’t know what’s going to.”

With more than enough “don’t knows” to go around, labs aren’t taking anything for granted.

Says Dr. Pritt: “We continue to prepare for the worst, hoping we won’t need to be in that worst-case scenario.”

Dr. Ginocchio agrees. “We have some very challenging times coming ahead of us. We’re just going to have to take it step by step.” And surge by surge, supplier by supplier, test by test by test by test.

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