NEW YORK – While it's unclear whether or not the US ever exited the first round of the SARS-CoV-2 pandemic, many fear another wave of infections could hit in the fall when the country will enter its typical high season for respiratory viruses.
Preparing for such a wave will present a number of challenges for the lab industry, foremost among them the continued difficulties around reaching sufficient test capacity and the issue of other respiratory infections like influenza complicating the diagnostic picture.
"You really have two components of testing that we have to think about," said Nathan Ledeboer, medical director of the microbiology laboratory at the Medical College of Wisconsin and Froedtert Hospital. "One, it's about having enough having enough capacity. Then number two, we'll now layer in all the additional respiratory viruses, in particular flu and RSV."
Given the similarity in terms of symptoms between these respiratory viruses and SARS-CoV-2, multiplexing will be a key consideration, Ledeboer said, noting that at Froedtert he and his colleagues have begun discussions on beginning to develop multiplexed assays so they can test for at least flu and SARS-CoV-2 in a single test.
"That is a major shift in how we test and what we test," he said. "We were really at the tail end of our flu season [when SARS-CoV-2 hit]. And the social distancing that was implemented really knocked off our flu numbers very quickly."
He noted that when pandemic-driven social distancing started, his lab was seeing around a 25 percent positivity rate for flu, which dropped to around 1 percent over the next two weeks.
The coming flu season combined with the SARS-CoV-2 outbreak will likely put further pressure on molecular testing capacities for both diseases, Ledeboer said.
"In starting to engage with our vendors [about the fall] they are basically telling us, yeah, we'll be able to supply you with flu tests at the same level we did last year," he said. However, he added, last year his lab ran only around 600 flu tests per week, while it currently runs around 1,500 to 2,000 SARS-CoV-2 tests per day. Multiplexing the two together won't be possible if the lab's flu testing supplies remain the same as the year before, Ledeboer noted.
"That's a huge problem, and nobody has really started to think that through yet," he said.
The reopening of hospitals for more routine care also complicates the situation, Ledeboer said.
"We support very, very large immunocompromised populations, and in those populations, we are very interested in the broader respiratory virus panels, because we isolate differently for those patients," he said.
For instance, he said, if an immunocompromised patient had respiratory syncytial virus (RSV) the hospital would treat that patient with the antiviral drug ribavirin. Being able to specifically determine what respiratory virus a vulnerable patient has is likely to influence treatment.
This raises the question of what access will look like this fall to broader respiratory virus panels, Ledeboer said.
To address these issues, he said his lab aims to expand the number of infectious agents it tests for while diversifying its testing supply chain to help avoid shortages.
"It's hard to predict whether flu will be bad [this year] or what the clinical implications may be," said Robert Boorstein, medical director at Brooklyn-based Lenco Diagnostic Laboratory. "But labs have to be prepared for physicians who are trying to sort out if something is the flu or coronavirus."
At the same time, he noted, labs are still working to manage SARS-Cov-2 testing while also working to bring their more routine testing levels back up to baseline.
"It's a complex environment," he said. "I think most laboratories will probably have flu-coronavirus testing options, but it will be a matter of reimbursement and ordering patterns that affect how they get used."
Boorstein said that most manufacturers of syndromic respiratory panels have testing that covers flu and SARS-CoV-2. Additionally, he noted, combination SARS-CoV-2-flu tests are coming online. Both Qiagen and BioMérieux's BioFire Diagnostics have received Emergency Use Authorization from the US Food and Drug Administration for tests that detect the coronavirus and influenza A/B viruses. Further, the US Centers for Disease Control and Prevention this month received FDA EUA for a molecular SARS-CoV-2-flu test. Meanwhile, Cepheid plans to launch a rapid 4-in-1 test for detection of the coronavirus, flu A, flu B, and respiratory syncytial virus from a single patient sample in Q3 of this year, and Roche said it will launch in the coming months a multiplex test for detecting SARS-CoV-2, flu A, and flu B.
"I think it will be interesting in terms of reimbursement and algorithms," Boorstein said. "Will insurers reimburse two tests upfront? Will they ask you to do them in some order? Would it be better to do flu first and then COVID, COVID first and then flu? If the flu is positive, will you not get reimbursed for a COVID test? I think all of those are questions that will be asked."
He said that while his lab has done fairly high volumes of syndromic panels during the last few flu seasons, "there hasn't been a lot of clarity around the use of syndromic panels with COVID, and I think people are reluctant to order a lot of them because they are afraid that there will be insurer pushback."
In response to questions about potential challenges of SARS-CoV-2 amidst a wave this fall, Pattie Kushner, Laboratory Corporation of America's chief communications officer, said the company is "aware of the potential convergence of flu testing on top of COVID testing, and [is] putting plans in place to address the demand for both tests, including utilizing various testing methodologies and platforms to manage potential volumes."
Quest Diagnostics spokesperson Kim Gorode said that the firm recognizes "that preparing for this year’s flu — along with other respiratory viruses that typically increase in fall/winter months — will require additional planning. We plan to align with CDC guidance by offering panels that test for both respiratory viruses and COVID-19 through a range of platforms, in addition to offering a variety of options for flu and COVID-19 testing, separately."
Capacity remains a major issue, of course, and will almost certainly still be a challenge in the fall when testing for employees returning to the workforce and students going back to school could spike demand even higher. The lab industry is already struggling to keep up with the demand generated by the current spike in SARS-CoV-2 infections. Last week, LabCorp said that its average turnaround time for SARS-CoV-2 tests was between three and five days while Quest said this week that its average turnaround time for high-priority patients was now more than two days, and for non-priority patients, the turnaround time was seven days or more.
The company also indicated that it was working to tamp down the flow of incoming SARS-CoV-2 test orders, noting that "the inflow of specimens to our labs has stabilized … due to our efforts to modulate orders for low risk patients."
In a recent interview with the Financial Times, James Davis, executive vice president at Quest said that PCR testing capacities would not be able to grow enough in coming months to meet anticipated demand.
On a conference call following the release of Quest's Q2 2020 financial results on Thursday, Steve Rusckowski, the company's chairman, CEO, and president, said that while the company expects to expand its SARS-CoV-2 molecular testing capacity from 130,000 tests per day to 150,000 per day in the next several weeks and to continue to build capacity in the months ahead, it was constrained by a number of factors, including access to instrumentation, reagents, and manpower.
He said the company was exploring a range of options to further boost testing capacity and highlighted the EU
A the company received last week from the US Food and Drug Administration for pooled SARS-CoV-2 testing.
Rapid antigen testing could help close the gap. Last week, the US Department of Health and Human Services said it was shipping instrumentation and tests for rapid point-of-care antigen testing to nursing homes in areas with high levels of SARS-CoV-2 infection. The agency will be sending Quidel's Sofia and Sofia 2 and Becton Dickinson's BD Veritor Plus instruments and rapid protein antigen tests developed for those systems, both of which have received FDA EUA.
BD said this month it expects it will be able to produce 2 million rapid tests per week by the end of September. Quidel has said it expects to be able to produce around 9 million rapid tests per month.