It was a chilly winter morning when the phone rang and Dr. Riccardo Valdez, Director of Clinical Pathology at Michigan Medicine, answered and heard the words, “Do we have a plan yet for this novel coronavirus, because I have a feeling it is going to really blow up.” It was Pathology Chair Dr. Charles Parkos on the line. This phone call radically changed the course for the Department of Pathology and this novel virus, which caused COVID-19, became the chief focus of the entire department. Valdez immediately contacted Dr. Duane Newton, who was the head of the microbiology and virology lab, asking him about plans for testing and lab support, and the rest is history.
“It wasn’t clear in the beginning what the impact would be,” said Dr. Michael Bachman, Associate Director of Clinical Microbiology. “We were reading in the news about cases in China and the concern that cases would emerge in the United States.” Previous health threats with Ebola and Zika Virus were handled by the CDC (Centers for Disease Control) and the state health labs assisted with identifying patients who had the virus. Initially, the plan was that COVID would be handled similarly. The FDA gave emergency use authorization to the CDC and state laboratories to do testing. “Initially, we felt that we would work closely with them so that samples would be sent to them for diagnostic testing,” explained Bachman. As soon as the FDA provided guidance for other laboratories to perform the testing, Parkos charged the molecular team with developing a COVID test.
Developing tests to quickly and accurately identify a novel virus was not an off-the-shelf solution. There were no commercially-available samples that were known to have or not have the virus. “Typically, we have well-characterized samples that we can use to validate a test. That wasn’t available. It was a struggle to even get materials that were known to have the virus in it, so we had to get viral RNA from a research laboratory in order to start validating the test,” explained Bachman. “We worked for 17 days straight to get that implemented. That involved trying to find materials we could use as controls, trying to get CDC reagents quickly, trying to make sure it would work on our existing platforms. There were things we weren’t sure about, like what kind of safety precautions we needed to take. It wasn’t clear how the virus spread. We thought we would have to heat deactivate all of our samples and put out requests for heat blocks for us to be able to do that. Then it became clear that that was not only unnecessary, but it was actually hindering the test, so we had to change directions.” The team successfully had the CDC test implemented within 10 days of the virus reaching Michigan.
It became clear pretty quickly that there were problems with the CDC assay, however. “The biggest stressor early in the pandemic was that the CDC test was the only test that was available and it was somewhat tedious and cumbersome,” said Parkos. “They didn’t get it right the first time.” COVID was spreading rapidly and “we knew we were going to need higher throughput testing and rapid testing, and those likely were going to be two different tests,” said Bachman. By that point, some of the diagnostic companies had come out with assays that were higher throughput or faster, so the laboratory implemented a couple of those. “We spent 17 days validating the CDC test and ended up using it for only 10 days,” recounted Bachman. “We moved through 3 different tests in less than a month.”
While testing was being developed in the laboratory, departmental leadership were trying to determine how to handle volumes in excess of what our laboratory could handle. “We began talking to Viracor, and they had tests up and running pretty quickly and that is one of the first COVID tests that we did,” said Valdez. “I remember being on a late-night call with Dr. Steve Kronick in the Emergency Department, Cybill Starr, our MiChart Liaison, Dr. Paul Lephart from our microbiology lab, and Beth Lawless from send-outs, to figure out how to organize tests for send out, how to name and code the test, how to determine when these would go out instead of being processed in our own laboratory, how to send them to Viracor, how many they could accept, and what the turnaround time would be.” There were many unknowns in the process including what the actual number of tests would be. “We just kept building capacity,” said Valdez.
One of the key drivers for decisions being made was diversity. Diversity of platforms, sample types, reagents – anything involved in the testing process. As a novel virus that was exploding across the world, there were severe supply shortages. Having a diversity of options enabled the department to continue testing. However, the nasopharyngeal swabs for obtaining the samples and the transport media for sending samples to the laboratories quickly became difficult to obtain. The supply shortage was due to multiple causes. “Manufacturing had their own challenges with staffing; there were raw materials issues,” explained Kristina Martin, Clinical Pathology Operations Director. “We were trying to be resourceful and look at all possibilities. When we couldn’t get the transport media, we outsourced to a compounding pharmacy and they made the collection tubes for us using a phosphate-buffered solution.” Calls went out to research laboratories and others who may have needed supplies in stock. “We tried to source them from China and tried to take advantage of opportunities of gifts that people were giving and something always happened,” Valdez lamented. “The shipment didn’t show up, or the shipment showed up and it was contaminated. We even tried 3D printing the swabs. A lot of effort in the department and the institution was just spent on trying to obtain the materials.” In an effort to conserve supplies, the microbiology lab began pooling samples for testing. Samples from five patients would be combined and tested. If the results came back negative, all five could be reported out as negative. If the results came back positive, the five samples would be retested individually. This helped the lab keep up with the high volumes as well as conserve supplies while getting test results back to patients more quickly.
The microbiology lab developed multiple tests to serve different purposes. After the CDC test was sunsetted, an assay called the M2000 was developed, but it was not sufficient to keep up with demand. “The ED (emergency department) patients needed a quicker turnaround, so we developed a test using the Diasorin Simplexa. We acquired more of those and validated those,” explained Valdez. “That became our STAT test with a 3-4-hour turnaround time. That was supplemented with point-of-care testing. Initially, we tried the ID-Now test, which was a 15-minute test, but that didn’t work because the swab that came with it wasn’t high enough yield for the virus. So we abandoned that and went another route for point-of-care testing.” The ED was being overwhelmed with patients. The 3-4-hour turnaround time wasn’t fast enough. They needed the results quickly so they could determine if patients needed to go to special isolation rooms or to standard rooms. “We eventually got them an accurate test that had results back in less than 1 hour and that was a game-changer for the ED,” said Valdez.
As volume increased to several thousand tests per day, the microbiology laboratory staff simply could not keep up with the demand. To provide additional capacity, the molecular diagnostics lab was asked to assist. “Bringing an infectious disease into the molecular diagnostics laboratory is not the type of testing they normally do,” stated Martin. “Jennifer Bergendahl (Administrative Lab Manager for the Molecular Diagnostics Laboratory) is to be commended for her can-do attitude in bringing on what normally doesn’t fit there – it really helped to ease the volume in microbiology. Then later, when all the variant testing started coming in, her lab was able to help with determining which kind of variant was causing the outbreaks. She was very systematic and figured out how to get it done.”
As the pandemic spread, University President Dr. Mark Schlissel asked the department to provide saliva-based testing for students. “We were already stretched pretty thin with testing for Michigan Medicine patients and employees,” recalls Parkos. “Developing a saliva-based test and adding another 30,000 tests per week was not going to be possible with the constraints we faced in staffing and equipment.” Parkos found the solution through Dr. Arul Chinnaiyan, who runs a very robust molecular platform in the department. Chinnaiyan was able to take the saliva-based testing protocol and onboard it at his UM start-up company, LinxDx, which was able to handle the high testing volumes.
Others stepped forward to help ease the burden as well. Laboratory staff and other departmental staff volunteered to help in any way they were able. Some unscrewed the specimen containers so others could aliquot the specimens for testing, while still others were busy labeling specimens. These volunteers would work their normal shifts and then, before or after their shifts, they would come to help. The MLabs call center team had phone calls for the laboratory routed to them so that the laboratory staff could do their work uninterrupted. Other staff ran specimens from the RICU (respiratory infection containment unit) to Specimen Processing. The Specimen Processing staff worked miracles in getting all of the thousands of additional specimens logged in each day. It was truly an all-hands-on-deck effort. “I want to give a shout-out to those working in the laboratories,” said Parkos. “Med techs and the folks in the trenches who were having to work overtime, night and day, to cross-cover for each other through this enormously stressful time. We would have been in a much more difficult place if the micro lab, for instance, said, ‘I quit, I’m not going to do this.’ But they didn’t. They came into work every day.”
There were other laboratory challenges the department faced. The Blood Bank was running out of blood for patients. There were no people to donate blood – everyone was staying home. All of the normal blood donation activities simply stopped. Early in the pandemic, hydroxychloroquine was thought to be effective against COVID. The hematology lab was asked to suddenly ramp up on a test for patients who were to get this treatment. While this test is normally performed once a week, now there were hundreds of tests to rule out a particular enzyme deficiency. This was at a time when the department was working on a “Lombardy schedule” – half of the department worked in the office while the other half worked from home in rotation, to limit exposure. The Chemistry lab was also tasked with developing and performing serology testing to test for antibodies to the virus. This was a whole new field for the laboratory team to learn. Then there were the researchers who wanted to study COVID. “Researchers were coming from everywhere wanting left-over swabs, left-over serum, left-over blood, and they wanted to come down to the lab to retrieve these samples,” stated Valdez. “We had Dr. Robertson Davenport, who is an IRB (Institutional Review Board) co-chair and a biorepository expert in our lab, coming in on evenings and weekends to try to pull COVID-related samples for researchers who were requesting this. This task typically falls to some of our laboratory staff, but they were overwhelmed with testing. So a senior faculty member came in on his weekends during a pandemic to retrieve research samples to support the institutional need.”
On the Anatomic Pathology side of the department, there were the autopsies and the management of the decedents that presented challenges. “One of the best tools we have in understanding a new disease is the autopsy itself,” explained Dr. Liron Pantanowitz, Director of Anatomic Pathology. “Doing autopsies, you can understand why the people died, what the disease is doing, and how that correlates to clinical findings.” Our morgue is equipped with negative pressure areas to help protect our staff when performing autopsies on those with infectious diseases. Dr. Allecia Wilson, Director of Autopsy and Forensic Services, really stepped up to perform autopsies on COVID-positive decedents. “She was quite brave,” praised Pantanowitz. “I don’t know how she plucked up the courage to say, ‘OK, I will do the autopsies to figure out what is going on and to get tissue for the researchers to start figuring out how to treat that disease.’ She didn’t send other people in to do the autopsies. She did them herself.” With the increase in the number of deaths due to COVID, storage of the decedents was another challenge. Early in the pandemic, before it actually became an issue, Christine Rigney, Director of Operations for the Division of Anatomic Pathology, had the foresight to prepare. “I was concerned about autopsy and forensic services,” she explained. “We had to make sure we had enough storage for our decedents if it affected us in the way we had seen it happening in other areas of our country or even overseas. So we had to get additional storage.” Rigney proceeded to locate and secure additional refrigeration units to be sure the department could properly care for our patients who died from COVID. “We had to be sure that we could care for these patients in a respectful manner. We needed to be able to assure their family members that their loved one was being handled with dignity.”
During the first wave of the pandemic, many clinics were closed and non-urgent operations were suspended. This helped to reduce some of the burdens on the laboratories, however, for the second and third waves, clinics were reopened and surgical centers were not just operational, but they had extended hours. The third wave of the pandemic was particularly challenging. “Following the first wave, the institution decided as part of the recovery to start operating on patients again, and the samples started to increase significantly,” recalls Pantanowitz. “It was like a rebound. With the recovery, there are more patients and more surgeries. In the last two months, there were two occasions in which we broke the record for the number of blocks accessioned – and we are supposed to be in a pandemic.” The operating rooms had expanded to include weekend hours and later hours during the week. In addition, the types of cases handled in the surgical outpatient clinics were expanded as well. “We had to deal with excess volumes with less staff due to COVID. People have various COVID issues to deal with, so we were short-staffed, especially in histology,” stated Pantanowitz.
The efforts of staff members were not overlooked. “I want to thank all the people in the laboratory, dealing with specimen processing and COVID testing. It really is a testament to their dedication to their work. They worked a lot of overtime, really long hours,” praised Bachman. “This has left me with a new level of admiration for the staff and faculty in our clinical laboratories, who, in many respects, are unsung heroes of healthcare,” said Dr. Jeffrey Myers, Vice Chair for Clinical Affairs. “One Saturday early in the pandemic,” he recalled, “I went down to the lab to see how they were holding up. I learned that one of the senior technologists who was developing COVID testing was staying at a hotel down the road instead of going home, so he could be closer to work and not risk not being able to return. Who does that? Where do you see that kind of commitment? That is amazing to me.” Myers continued, “There is a lot to grieve with the pandemic, but there are some things to celebrate and our people are number one.”