College of American Pathologists
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Keeping cool-headed in the face of SARS

June 2003
Cover Story

Karen Titus

This is a story about SARS—specifically, how to handle SARS or suspected SARS specimens in the laboratory.

Ho hum.

That’s not to diminish the harm wrought by the disease, nor to make light of the threat it poses. Nor is it meant to undermine the considerable fears it has unleashed among laboratory workers.

But even in the most severely affected site in North America to date, Toronto, it’s hard to elicit dramatic statements about the impact SARS specimens have had on lab logistics. And at the Centers for Disease Control and Prevention, certainly one of the flash points for information about the disease, matter-of-factness has been the order of the day. As of late May, laboratory workers appear to be remarkably safe even in Asia, where SARS has been raging among health care workers and patients alike.

“Based on our experiences over the last couple of months, with thousands of specimens in multiple countries, we have yet to document a laboratory-acquired infection,” says Rob Weyant, PhD, chief of the laboratory safety branch in CDC’s Office of Health and Safety, who helped author the CDC’s interim lab biosafety guidelines for handling and processing SARS-related specimens. “We believe the risk of acquiring disease via a laboratory specimen is probably lower than the risk of taking care of a patient.”

Luck has nothing to do with it. The reasons laboratory workers have been safe—so far—appear to be rooted in solid adherence to standard (formerly known as universal) precautions. At the same time, however, labs face a frightening number of unknowns about the disease and a crushing amount of information as they continue to prepare for potential SARS cases.

“It changes on a daily basis. It changes on a minute-to-minute basis,” says Barbara Robinson-Dunn, PhD, D(ABMM), technical director of microbiology, William Beaumont Hospital, Royal Oak, Mich.

“The CDC has sent out an overwhelming amount. Not only that, but the state health departments send out guidelines, too,” says Steven Dallas, PhD, D(ABMM), director of microbiology, Presbyterian Healthcare, Charlotte, NC. “Then the county will give you information, so you quickly get overwhelmed and say, ‘Which one of these 30 bulletins should I keep?’ Probably better too much information than not enough, though.”

At Mount Sinai Hospital in Toronto, the unknowns could hardly have
been greater when the public health authority sent its directives in April in response to the unfolding SARS crisis: Two hospitals would be shut down and two—including Mount Sinai, which had handled the city’s early SARS cases and was caring for numerous SARS patients—would be placed on severe restrictions.

“When the restrictions came, they came with virtually no notice,” recalls Kenneth Pritzker, MD, FRCPC, pathology chief and director of pathology and laboratory medicine, Mount Sinai, and professor of laboratory medicine and pathobiology, University of Toronto. The mandate put a hold on all but essential services at Mount Sinai and the other restricted hospital; those not performing essential services were to stay away.

Though one reason for the directive was to limit spread of the virus,
“The primary consideration was that the screening procedures [to enter the hospital], which were instituted on an instantaneous basis, were quite elaborate,” says Dr. Pritzker. “And it was rather important to keep down
the number of people going through those procedures, so we could get the people performing the essential functions into the hospital to do their duties.”

The mandate, which also instructed hospital personnel to wear masks, was issued at 7 PM one evening; by midnight, all the hospitals had complied. And although the bulk of patients and staff don’t appear until the start of the 7 AM shift, the impact should not be underestimated.

“You have to understand the size of the screening magnitude,” Dr. Pritzker says. The screening process has involved some 30 screeners, plucked from hospital staff—including laboratorians—working at three different stations, where arriving employees filled out epidemiology questionnaires, performed prescribed handwashing, and had their temperatures taken. “So the drain on our staffing was very, very substantial,” he says. Separate screening procedures were set up for visitors and at exits.

The less traffic the better, obviously. But while other departments were cutting back, the laboratory kept its numbers high. “We made a decision—and it was a fortunate decision to make—that all the services that we were providing were essential. We did this because we really did not know what our volumes were going to be, or where our specimens were going to be coming from,” says Dr. Pritzker, noting that in addition to handling specimens from SARS patients, they continued to provide testing for inpatients and urgent outpatients, including patients in the hospital’s high-risk pregnancy unit. “Those kinds of things don’t wait,” Dr. Pritzker notes. They also knew that as soon as the crisis passed, they would face a flood of specimens. Only a small number of lab staff were excused from work during the first two days—not because of any imminent danger, but in response to the initial pressures to reduce staff.

“If we were to do anything differently, we wouldn’t have kept anybody in our services out, even for that 48 hours,” Dr. Pritzker says. “Every one of our staff would be asked to be there from the outset and would be put in a redeployable situation.”

For all the “Andromeda Strain” dramatics unfolding, however, the
laboratory has teetered on the edge of calm.

The most reasonable lab concern—how to handle SARS-related specimens—has actually been one of the least problematic issues for Mount Sinai’s laboratory. “The first thing we can tell you is we’ve been handling the specimens exactly the way we’ve been handling specimens prior to the SARS crisis,” says Dr. Pritzker. All the lab’s policies and procedures are geared toward standard precautions—any specimen coming from any site is considered potentially infectious. “We try not to differ for any particular group of patients. So that’s what we did in terms of the SARS patients,” he says.

The laboratory benefited from other standing procedures. Specimens from the intensive care and inpatient units are collected by those working in those units. Since the SARS-affected hospitals were trying to limit traffic in and out of units with SARS patients, the policy paid off. “This allowed the specimens to come to us without difficulties,” Dr. Pritzker says.

Specimens also continued to arrive in the lab via the hospital’s pneumatic tube system, per usual. Specimens traveling this route are routinely double-bagged, so if a spill occurs, it is contained immediately. But that has happened exactly “never,” says Nancy Hutton, technician, patient services supervisor at Mount Sinai.

At the same time, because of the tight screening restrictions, the laboratory had to quickly revamp how it received specimens from outside the hospital, directing couriers—who were no longer allowed into the hospital—to specific entry points. “It might sound trivial, but it certainly was not,” says Dr. Pritzker. “Every day we receive specimens from as many as 10 sites outside the hospital. So just getting organized was an effort.” Some of Mount Sinai’s ambulatory facilities also closed briefly, but the patients who visited those sites had urgent testing needs that had to be handled at Mount Sinai’s lab. As if SARS weren’t a heavy enough load, the region was socked with an ice storm at the same time. “Fortunately, almost every specimen that was supposed to arrive here and get processed did so successfully,”
he says.

Such adjustments point to the real problem Mount Sinai’s laboratory faced—how to look beyond SARS in the midst of the crisis. As Dr. Pritzker notes, potential disruptions to laboratory services are not new. Labs have to cope with everything from AIDS to hepatitis to electricity blackouts. “The key from the laboratory perspective is to pay very close attention to preventive maintenance and to drills and procedures so the staff can actually cope with the crises well, as soon as they come up.

“If we hadn’t been doing this kind of thing for years, we would have been faced with much greater problems,” he says.

That’s not to say there weren’t SARS-related concerns, or that such concerns have disappeared entirely. “The anxiety by the staff was quite considerable,” says Dr. Pritzker. “Appropriately so, because we had staff within this hospital who were working directly with the first SARS patients.” The small group of lab workers who had been excused in the first 48 hours were especially nervous—they thought they’d been sent home because the workplace wasn’t safe.

From the outset, Dr. Pritzker and his colleagues, along with the managerial staff, met those fears head-on. “We had to be out in the laboratory, talking with groups large and small, outlining for them, as best we could, what the situation was and letting them know that under no circumstances would we place them in any known danger,” Dr. Pritzker says.

It wasn’t easy. Fear swept over many staff when the edict came down for everyone in the building to wear masks—at the time, no one knew how SARS might be spread, and the concern was that anybody could be carrying it. “One of the hardest problems was trying to explain to the lab staff why they were wearing masks—in microbiology, pathology, chemistry, wherever—when they had no patient contact,” says Tony Mazzulli, MD, FRCPC, deputy chief, microbiology, Mount Sinai.

Dr. Mazzulli and other leaders were inundated with questions from lab workers, and trying to address them all proved to be one of their biggest challenges. But doing so helped keep the lab running smoothly. Many questions were occupational in nature. “Maybe they had young children or elderly parents at home, and some people were on forms of immunotherapy for a variety of diseases—and they all wondered if they’d be safe,” Dr. Mazzulli says.

Talking about safety wasn’t enough—lab leaders took the extra steps of showing their staff that the safety procedures were working. For example, lab hoods that are exhausted were checked again, even though they had recently passed inspection, as was airflow in the autopsy room. “At the outset we went through all our procedures to make sure they were, in fact, being done,” says Dr. Pritzker. “They were actually seen, by our staff, being done. That was a big part of the reassurance process. And since this is a fairly large laboratory, this had to be done in many different corners by people who know their areas well. And this assessment was done in a matter of hours.”

Throughout the ordeal, it was never clear how far the virus would spread, nor what, exactly, would be required of staff in responding to the crisis. “Our people had to make decisions on their own in order to expedite services, because things were changing so much,” Dr. Pritzker says. “Fortunately, it all went very, very smoothly, which indicates that staff on the whole have been very well trained. They’re capable of handling surprises and situations where they don’t know all the answers.”

Though Dr. Pritzker sounds justifiably proud of his institution’s quick response to SARS, he doesn’t hesitate to credit preparations that occurred far earlier. “All these kinds of things can only happen if the table has been set a long time back, and as you conduct practice sessions. The preparation for these things is not when you have a crisis. The time to do this is when things are calm.”

Most laboratories have not endured the SARS trial by fire that
MountSinai has, but they’re doing their best to prepare themselves
for the worst.

At Methodist and Children’s hospitals, Omaha, the microbiology laboratory—which splits services between the two institutions—underwent a dry run for SARS specimens in mid-April, reports Nancy Cornish, MD, director of microbiology. The timing couldn’t have been better, since two days later they had a suspected SARS case—a Toronto physician who arrived in the ER with respiratory symptoms and requesting a mask. “Everything went like clockwork,” says Dr. Cornish. The lab was notified, the Directigen tests were done in Methodist’s TB room, and the viral culture specimens were sent to the public health lab. “Everybody was properly gowned, wearing the right masks and working in the right room, and everyone knew what to do,” she says.

The dry run allowed Dr. Cornish and her colleagues to alter several practices. For example, they decided not to do their direct fluorescent antibody testing for influenza A, B, and RSV at the Children’s virology laboratory, which contains a biosafety level two facility. “With fresh unfixed specimens we wanted a level two with bio three precautions, and I wanted a negative airflow,” Dr. Cornish explains. In moving the DFAs over to Methodist, however, they discovered that doing them under the hoods was too cumbersome; they also wanted to avoid hauling the needed equipment from Children’s to Methodist. “We finally decided to go with the Directigen, which is a rapid test, and use it under the hood,” she says.

Like other laboratorians, Dr. Cornish and her colleagues are trying to balance the CDC, state, and other guidelines with the nuts and bolts of their daily operations. “If we were going to err, we tried to err on the side of doing a little too much. There’s no such thing as being too safe,” says Dr. Cornish. “But we also had to be practical, given how our workflow goes.”

Certain specimens are worked up in the TB room—which has a negative airflow—in a class two biosafety cabinet hood. Workers handling those specimens wear N95 masks, a solid-front gown, and gloves and eye protection. “This is for anything that requires aliquoting or dilution of specimens, uncapping of vacuum tubes, anything that could produce an aerosol or splash,” says Dr. Cornish.

The lab also considered how to work up routine specimens from possible SARS patients. The CDC recommends using standard precautions for routine serology, chemistry, hematology, and other tests; laboratorians should wear protective gear, Dr. Cornish says, including gloves, solid-fronted lab coats, eye protection, and a surgical mask. “If they’re going to be doing anything with aerosols, then they would have to do that under a hood,” she says. “Once it gets loaded into the chemistry analyzers, then we feel it’s OK—those are closed systems.”

Specimens for microbiologic analysis present their own dilemmas. The infection control team is supposed to notify the lab of any suspected or probable SARS cases; in turn, the lab has asked that specimens in those cases be identified with a hot-pink label reading “SARS,” which will be placed on the outside of biohazard bags for everyone to see, as well as on requisition forms.

The labs would work up fresh tissue or fluids under hoods that meet biosafety level two qualifications, as well as specimens for routine staining. “So we’d make Gram stains under a hood,” Dr. Cornish says. “In fact, we’d aliquot the specimen under the TB hood, because it can be aerosolized. Then once it’s fixed, it is handled using standard precautions.”

The morgue, surgical pathology room, and TB room are the institutions’ only negative-pressure rooms. “I get a little worried when I think about someone handling a possible SARS specimen in a class two hood in the middle of a busy lab where there’s no negative pressure,” Dr. Cornish says. The TB hood, on the other hand, is sequestered, away from traffic flow. “It’s probably the safest hood we have.”

The basic strategy in a possible SARS case, then, is to handle unfixed fluid and tissue specimens in the TB room. Failing that, the goal is to move the worker into a negative airflow room and make sure she or he is wearing an N95 mask. Viral cultures would be sent to the public health laboratory, which has a full biosafety level three facility.

“It’s a little confusing, I think, to try to follow all this,” Dr. Cornish concedes. “But we’re doing the best we can. And if we have an outbreak situation, well, then we’d all have to reconvene and discuss how to handle that.”

The CDC’s guidelines, posted on the agency’s Web site, are the
startingpoint for most discussions about handling SARS-related specimens. The guidelines have gone through multiple iterations, evolving as new information becomes available. That, in turn, creates potential for confusion, the CDC’s Dr. Weyant acknowledges. “We learn something new about this virus every week,” he says.

At the same time, he emphasizes that the biosafety level two guidelines cited in the April 16 interim SARS guidelines are standard practices in hospital microbiology labs already: no eating, smoking, or drinking in the laboratory; washing of hands; no mouth pipetting. “These should already be in place,” he says.

Handling specimens in nonmicrobiology labs gave them pause early on. “We really wrestled with this,” says the CDC’s Betty Robertson, PhD, deputy associate director for laboratory science. The data thus far indicate the virus may be present in blood, though it’s unclear what the level of viremia might be.

But the matter may be more simple than some labs have feared, Dr. Weyant says. “We say in the guidelines that blood and urine specimens can be handled using standard precautions in BSL2 laboratories, and then we specify the protective equipment that’s needed, which includes disposable gloves, laboratory coats, eye protection, and surgical masks or face shields.” The guidelines do not recommend aliquoting blood and urine in a safety cabinet, he emphasizes. That particular recommendation is for the area referred to in the guidelines as “other specimens,” which would “presumably be from sources where we would expect to find a higher titer of virus, such as respiratory specimens.”

With blood and urine specimens, adds Dr. Robertson, “We feel like the risk is minimal.” But, as the guidelines demonstrate and as many laboratory directors suspect, “We tried to err on the side of caution,” she says.

The interim guidelines suggest that laboratories turn to “administrative measures and/or additional personal protective equipment” if safety equipment recommended in the guidelines is unavailable—a vague-sounding phrase that’s caused consternation in at least a few laboratories.

“What we were thinking of,” says Dr. Weyant, “is, if necessary, limiting
the number of people in the laboratory during a higher-risk procedure”—
for example, centrifuging suspected SARS specimens using an instrument without safety cups or sealed rotors, with no recourse to a biosafety cabinet. In such cases, labs could relocate the centrifuge to a low-
traffic area.

Suspected SARS specimens should be labeled as such, Dr. Weyant says, clarifying another issue—as some laboratory directors have noted, standard precautions instruct labs to handle every specimen similarly, without such labels. “If there is a patient in the hospital in whom SARS is suspected, there should be good communication with the lab, so the specimens can be flagged and handled appropriately,” says Dr. Weyant.

The guidelines are a work in progress. Early versions had more stringent suggestions for respiratory protection, for example; as the CDC talked to more laboratorians and gained experience working with specimens, the guidelines became more flexible, allowing lab managers to make risk assessment-based decisions.

Dr. Weyant uses the word “flexibility” frequently when he discusses the guidelines. The authors tried to consider every possible scenario, he explains, from basic triage laboratories to sophisticated laboratories. They’ve had to provide guidelines despite a tremendous lack of data. Laboratory supervisors and safety officers have to take into account their own situations, equipment, and procedures. In each case, flexibility was
the watchword.

“These guidelines are designed to help labs perform a risk assessment,” he says. “They’re meant to give enough flexibility to do that.”

And they do, says Dr. Robinson-Dunn, of William Beaumont. “You take what’s in the guidelines and you say, ‘Does this apply to me? And what
do I need to do? What’s being recommended? And is this feasible or
not feasible?’”

Adds Jared N. Schwartz, MD, PhD, chair of the CAP Ad Hoc Committee on Preparedness for National Emergency, “There’s a reason the CDC calls these ‘guidelines.’”

The focus on SARS may be counterproductive if taken too far—
a little like someone losing sleep over terrorism, then failing to fasten his seat belt in the car. As they consider possible SARS scenarios, labs are discovering that the two best tools at their disposal are common sense
and experience.

“Our initial thoughts were this: that standard precautions work for everything so far,” says Presbyterian’s Dr. Dallas, pointing to TB, hepatitis C and B, and HIV. “We can prevent all kinds of infectious disease just using the biosafety level two workplace practices we always do. So unless this really is the virus from hell, I don’t see why we should change things.”

Other pathologists weigh in with kindred opinions. Robert Novak, MD, chair of the CAP Hematology/Clinical Microscopy Resource Committee, suggests that for blood specimens, no special treatment is required beyond the standard precautions recommended by CDC. “In terms of how the laboratory responds to any emerging infection, I think that standard precautions will be what general diagnostic laboratories will have to go with until these are shown to be inadequate.” Anthony Killeen, MD, PhD, who chairs the CAP Chemistry Resource Committee, says, “Basically, all samples are treated as potentially infectious. We don’t have any additional precautions for SARS in chemistry samples.”

Frankly, many laboratorians sound more concerned about non-SARS cases. “We don’t want to shortchange patients,” Dr. Dallas says. Possible SARS cases may also be RSV, or the flu or an adenovirus—in fact, they most likely would be, he says. “As they say back in school, if you hear hoofbeats, look for horses. So we want to look for the normal respiratory pathogens to make sure we get things diagnosed appropriately.”

“These public health concerns, which are on the outside of our hospital, distract from taking care of the sick people in our hospital,” he says. “Not that we shouldn’t prepare for it, but it really does take a lot of our mental energy away from the acutely ill people we already have in our ICU.”

SARS discussions, however, have enabled laboratories to review basic procedures and shore up areas that may have been weak. “It became clear we needed to do a much better job of making sure people understood the difference between different kinds of masks,” says Dr. Schwartz, director, Department of Pathology and Laboratory Medicine at Presbyterian. Not everyone knew, for example, that the recommended mask was the N95—and that this particular type must be fitted to the wearer. Likewise, he and his colleagues have used the situation to remind new and part-time staff of standard lab procedures, and to make sure they know whom to contact if they have questions. “We want to make sure every employee has a comfort level and understands they’re not going to be left on their own,” Dr. Schwartz says.

Like many others, he sees a potential upside to SARS preparations. If not SARS, it will be something else, he figures, so taking time now to prepare for the worst is the only sensible thing to do. Indeed, few laboratorians limit their SARS discourse to SARS. West Nile virus, Ebola, bioterrorism, avian influenza, anthrax, and the Norwalk virus all inspire worried musings—even from those who’ve been hit hard by SARS.

“Today the urgency is SARS. But tomorrow it’s going to be something else,” says Dr. Pritzker.

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