Yale School of Medicine adapts to the COVID-19 pandemic

The COVID-19 outbreak forced the Yale medical community to remake clinical care, research, and education at almost unimaginable speed. Doctors and nurses played new and unfamiliar roles; patients were moved between hospitals or cared for by video link. Surgeries were postponed and labs closed. Methods of educating students changed significantly, and some researchers turned on a dime to study the disease. And everyone Zoomed—a lot.

It was trial by fire for Nancy J. Brown, MD, the Jean and David W. Wallace Dean of Medicine and C.N.H. Long Professor of Internal Medicine, whose job began in February. “There’s nothing like a good crisis to help you learn an institution quickly,” Brown said. What has impressed her most about her new school? “How committed and generous our faculty and staff have been, how willing to pitch in, how collaborative they are,” she said. “It’s been really a pleasure to see people rise to the occasion.”

The Clinical Response

On March 13, the first COVID-19 patient was admitted to Yale New Haven Hospital while the Department of Internal Medicine had already been preparing for a month, led by its chair Gary V. Desir, MD, Paul B. Beeson Professor of Medicine.

Beginning in mid-March, elective procedures were postponed across the health system, freeing 700 inpatient beds. The move also preserved precious personal protective equipment. Led by Gail D’Onofrio, MD, MS, chair and Albert E. Kent Professor of Emergency Medicine and professor of epidemiology (chronic diseases), and Andrew Ulrich, MD, professor of emergency medicine and vice chair of operations—along with a multidisciplinary taskforce—the emergency department rapidly developed new protocols for patient flow and the safety of patients and staff, including outdoor triage tents. Developing innovative techniques for high-risk procedures such as intubations, along with the constant adaptability of the staff, reduced exposures and improved patient care.

Hospital authorities decided to house COVID-19 patients on the top three floors of Smilow Cancer Hospital, which were originally built to allow for negative-pressure ventilation if necessary. Cancer inpatients were transferred one by one via ambulance to the Saint Raphael campus. The move from her workplace on the 14th floor went smoothly, said Maggie Zampano, RN. “It was a beautiful dance. There was not one thing chaotic about it,” she said, “because all the oncology floors came together and worked as one for the greater good of our patients.”

Within minutes of the final patient’s departure, Zampano added, electricians arrived to prepare the unit for COVID-19 patients. “That’s how quickly Yale reacted,” she said. Additional COVID-only units were set aside at the York Street and Saint Raphael campuses.

Thanks to a backup-staffing plan led by Lynn Tanoue, MD, MBA, professor of medicine (pulmonary) and vice chair for clinical affairs (internal medicine), numerous Yale physicians stepped up to help the Department of Internal Medicine take the lead in caring for COVID patients. By late March, Tanoue was calling for additional ICU volunteers, saying it was an “unprecedented, all-hands-on-deck situation, which will require the united efforts of all our physicians.”

The sickest COVID-19 patients can have an outsized effect on hospital capacity. Normally, patients in the medical intensive care unit (MICU) experience three- to four-day lengths of stay, according to Jonathan M. Siner, MD, associate professor of medicine and then-medical director of the MICU. But by late March, it emerged that COVID-19 survivors’ average stays lasted 14 to 21 days, while those who did not survive typically were there for seven days before succumbing. Those statistics worried Siner and other critical care specialists. “You don’t necessarily need to have that many more admissions per day [to affect the ICU] if the length of stay goes up by that degree,” Siner told a Dean’s Workshop audience on March 31, as he described the Section of Pulmonary and Critical Care’s shift to a quasi-wartime footing.

Attending physicians who specialize in pulmonary and critical care led teams of attendings with less ICU experience. In all, nearly 200 attending faculty, residents, and fellows from the departments of Anesthesiology, Neurology, Dermatology, Pathology, Surgery, Radiology, Psychiatry, and Pediatrics cared for COVID-19 inpatients, along with dozens of community physicians. Infectious-disease physicians played a stewardship role, reviewing charts and advising each patient’s physician.

For frontline providers, the work was grueling. Because many consultants were working remotely and most visitors were no longer allowed, it could be isolating, too. Gary V. Desir, MD, chair of internal medicine and Paul B. Beeson Professor of Medicine, said, “There’s much less foot traffic on the floors. All the doors are closed. The hallways are empty. It’s a very different place compared to the bustling atmosphere when you work on the medicine floor” in normal times. Some clinicians working multiple long shifts or who needed to self-isolate away from family slept in hotels in downtown New Haven, their rooms covered by the medical center.

To help providers manage the stress of COVID care, the psychiatry department arranged for virtual stress and resilience town halls, a web-based hotline, and peer support.

By Tuesday, April 7, admissions and discharges of COVID-19 patients were beginning to balance out—a hopeful sign. At last, on April 13, Yale Medicine CEO and Deputy Dean for Clinical Affairs Paul A. Taheri, MD, MBA, reported that the number of inpatients was declining. Field hospitals of last resort went unused.

“As predicted, we are now in the midst of the anticipated surge of COVID-19 patients and expect to remain so for several weeks. Our planning has paid off and operations are running smoothly,” Taheri commented on April 15.

“Those beds [in Smilow] filled up, they filled up, they filled up. It was kind of like watching water in a bathtub. It came right up to the top, but it didn’t overflow,” said Edward H. Kaplan, PhD, the William N. and Marie A. Beach Professor of Operations Research and professor of public health and of engineering.

Telehealth, where doctors can see patients virtually without an office visit, has long been seen as the treatment option of the future, with years of pilot programs looking to pave the way. With the COVID-19 emergency, which increased concerns about in-person visits to medical offices and made it crucial to conserve PPE, telehealth took off, with thousands of outpatient visits that had previously been conducted almost exclusively in person now being done via video or phone. “We converted to 30% telehealth within the span of a month—it was amazing,” Desir said. While, in January, only 100 telehealth visits took place, in March their number approached 7,000, in April there were nearly 25,000, and in May there were more than 28,000 such visits. By June there was an average of 1,200 visits per day, and total telehealth visits for all of 2020 exceeded 500,000.

Clinical Studies

Many clinical studies went on hold, although those that involved patients receiving drug infusions for such diseases as cancer did continue.

With a pressing need to better understand how the virus affects patients, researchers and clinicians scrambled to stand up new studies. By May 19, a vastly busier institutional review board had approved more than 180 new COVID-related human-subjects protocols or adaptations to existing protocols, meeting seven days a week to go over proposals. “To the great credit of the institutional review board, they were basically meeting every day by Zoom, doing accelerated reviews so that researchers could get started on COVID-related studies,” noted Brian R. Smith, MD, the deputy dean for scientific affairs (clinical departments); professor and chair of laboratory medicine; professor of biomedical engineering; and codirector of the Yale Center for Clinical Investigation (YCCI).

Smith added that it also had been especially important to understand how COVID-19 affects Black and Latino patients, who have suffered higher numbers of hospitalizations and deaths due to the virus. Through its longstanding Cultural Ambassadors program, YCCI connected with these communities effectively. “We held town halls with our partners from the African Methodist Episcopal Zion Church and Junta for Progressive Action to listen to their concerns,” he said. “They were able to help distribute masks and health literature to their constituents, and also provide valuable leadership on how to engage them in clinical research. They have been instrumental full partners in directing and driving our research agenda.”

Versatility

Infectious disease specialist Mahalia Desruisseaux, MD, associate professor of medicine (infectious diseases), never thought she would find herself leading a hematology study. In addition to seeing patients, she normally had run a lab that investigates cerebral malaria. Desruisseaux had arranged to take time off from clinical work to focus on that research. Then her lab had to close as part of a university-wide safety protocol, a situation that made her feel useless.

“I had slated that time to do lab work. Then not only was I not on the floor seeing patients, but I wasn’t doing research,” Desruisseaux said.

When she learned the U.S. Food and Drug Administration (FDA) was authorizing emergency access to convalescent plasma for COVID-19 patients, she signed on as a principal investigator for a clinical safety study. “It was very therapeutic to do this,” she said. “I did feel like I was actually doing something to help.”

Desruisseaux’s was in the majority of research labs across the university that were forced to close because of the need for physical distancing.

“Obviously in a research lab, you’ve got lots of people crowded around,” Smith said. “All of that came to a halt.”

Some labs were able to change course to study COVID-19. In fact, the pandemic seeded an extraordinary network of collaborations among researchers at the School of Medicine and across the university.

Dean Brown founded the COVID-19 Response Coordination Team (CoReCT), which fostered collaborations among clinicians; researchers from the Yale Schools of Medicine, Nursing, Public Health, and Engineering; and social scientists affiliated with the Yale University Faculty of Arts and Sciences or with the Tobin Center for Economic Policy. Smith called CoReCT “terrific,” adding that “people who really may not previously have known [that each other] existed suddenly began talking about research they could do together.”

In early March, researchers on the medical campus founded a laboratory working group that came to be known as IMPACT (Implementing Medical and Public health Action against Coronavirus, [Connecticut, CT]). It was headed by Albert Ko, MD, professor and chair of epidemiology (microbial diseases) at the School of Public Health, and professor of medicine (infectious diseases). The group began to test patient samples for the coronavirus, characterize the virus, and map the human immune response.

“In our work at Yale, we had a giant head start” because of a preexisting collaboration between Ko and Akiko Iwasaki, PhD, in the Department of Immunobiology,” said Ruth R. Montgomery, PhD, professor of medicine and of epidemiology (microbial diseases); director of the Yale CyTOF Facility; and associate dean for scientific affairs.

“Because Albert is a real live epidemiologist and had very recently been through the Zika epidemic in Brazil, he knows how to handle an outbreak,” Montgomery said. “They just jumped fast.”

Montgomery’s own lab made a “natural pivot” to COVID-19, she said, since she studies human responses to viruses. Using high-throughput technology and advanced computational analysis, she began to study the proteins produced by COVID-infected airway cells.

Testing was an urgent problem, and Yale’s Department of Laboratory Medicine rose to the challenge. In late February, Marie-Louise Landry, MD, professor and vice chair of laboratory medicine, professor of medicine (infectious diseases), and medical director of Yale’s Clinical Virology Laboratory, began working to create a reliable version of the CDC’s diagnostic test adapted to the equipment available on site. It was a process fraught with difficulties regarding regulations, obtaining scarce reagents, and most important, getting access to the virus to validate that the test would be accurate.

By mid-March, Landry, supported by IMPACT and working with David Ferguson—her former lab manager who returned for the assignment—and the clinical virology molecular leadership staff Robin Garner and Jody Criscuolo, had created and validated an in-house COVID-19 test. It was the first laboratory-developed COVID-19 molecular test outside of a national reference laboratory to receive emergency use authorization from the FDA. Testing went live on March 13, and the first Yale New Haven Hospital patient to test positive was diagnosed that same day. The Yale Virology Lab was soon testing hundreds of people a day.

The effort to refine testing did not stop there. In August, a saliva-based laboratory diagnostic test created by researchers at Yale School of Public Health received an emergency use authorization by the FDA. SalivaDirect was developed by Anne Wyllie, PhD, associate research scientist in epidemiology (microbial diseases), Nathan D. Grubaugh, PhD, assistant professor of epidemiology (microbial diseases), and other members of Grubaugh’s lab, and validated as a test for asymptomatic individuals through a program that tested players and staff from the National Basketball Association. It is simpler, less expensive, and less invasive than the method that was most widely used earlier in the pandemic, known as nasopharyngeal swabbing. “We simplified the test so that it only costs a couple of dollars for reagents, helping to make large-scale testing more affordable,” said Grubaugh.

Meanwhile, IMPACT built a biorepository of clinical samples from health care workers and COVID-19 patients. This library has become a rich resource for researchers studying immune responses to the virus.

Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology and Molecular, Cellular and Developmental Biology and Howard Hughes Medical Institute investigator, formed numerous collaborations to study the human immune response to the virus, including with Ko, Grubaugh, and Craig B. Wilen, MD, PhD, assistant professor of laboratory medicine and of immunobiology and medical director of the Immune Monitoring Core Facility. Wilen studies how the virus infects airway cells, how it compares to other lethal coronaviruses, and which human genes permit infection.

Though some federal grants became available, funding was, for many, a scramble. Discretionary departmental and medical school funds covered some expenses, while private donors stepped up to pay for others. Wilen’s experiments required that he upgrade some equipment in Yale’s biosafety level 3 containment lab. Thanks in part to alumni, Dean Brown came up with funding the same day, he recalls.

Many other researchers studied the pandemic from home offices. Kaplan, for example, created “scratch” mathematical models to predict the course of the local outbreak; his results helped inform the university’s decisions about re-opening.

Summer was the time when clinical trials to evaluate the safety and efficacy of COVID-19 vaccines proceeded in earnest. Led by principal investigator Onyema Ogbuagu, MBBCh, associate professor of medicine, Yale ran clinical trials for the mRNA vaccine developed by Pfizer and Germany’s BioNTech. Efforts by Ogbuagu and colleagues, and those who volunteered for the trials, helped establish a 95% efficacy rate for the vaccine and a strong safety profile. On December 11, the Food and Drug Administration gave emergency use authorization to the vaccine, and three days later vaccinations began in New Haven and other locations around the country. Ogbuagu said he was thrilled to be one of the first recipients. “You study a drug, you find out it works, and then you become part of receiving it yourself and experiencing the benefit.”

Testing / Screening / Safety

As early as January 2020, the Yale New Haven Health System began laying in extra supplies of PPE. In February, it began buying them from the industrial sector. New protocols reduced the rate at which PPE was used up and discarded, but the need to conserve it grew so pressing that it contributed to halts in elective surgeries and student clerkships.

With most operations in her department postponed for the duration, Lisa L. Lattanza, MD, professor and chair of orthopaedics and rehabilitation, threw herself into the battle to secure more PPE. With the usual vendors unable to meet demand, she fielded and made countless phone calls about possible sources, always weighing the risk of receiving PPE that was fraudulent or ineffective. Lattanza worked with the Coalition for Health Innovation in Medical Emergencies, an initiative of Yale’s Center for Engineering Innovation and Design, to develop a way to test whether donated and third-party N95 and KN95 masks were safe to use. She also worked with Connecticut manufacturers of sporting goods and other consumer products to repurpose their plants to create masks, face shields, and gowns.

Patrick A. Kenney, MD, assistant professor of urology and clinical vice chair of Yale Medicine Urology, is the medical director of corporate supply chain for YNHHS. Kenney led a team including Richard A. Martinello, MD, associate professor of pediatrics and of medicine (infectious diseases), and medical director, infection prevention; Mark Russi, MD, MPH, professor of medicine (occupational medicine) and of epidemiology (environmental health); and Ben Chan, PhD, research scientist. They demonstrated that vaporized hydrogen peroxide is able to eliminate virus on respirators. A reprocessing facility was rapidly built with the capacity to reprocess more than 200,000 respirators per week. It was used to sterilize respirators for YNHHS and other entities including Emergency Medical Services. Kenney’s team also sourced thousands of elastomeric respirators, crafted a sterilization and distribution plan, and deployed them across multiple sites of care.

Efforts to reduce PPE utilization, such as by care redesign and extended use of respirators, had a dramatic impact including a roughly 90% reduction in respirator burn on a per patient basis compared to baseline. Based on the successful efforts of YNHHS Supply Chain, Kenney was asked during the crisis to provide information and advice to Vizient membership, the U.S. Defense Logistics Agency, the World Bank, and FEMA.

Education From Home

On March 11, the university asked students not to return to campus after spring break, announcing that classes would resume online. Within a week, faculty and the Office of Education had created remote-learning experiences for medical and physician associate students—a “heroic” effort requiring intensive faculty training in the online tools, said Michael Schwartz, PhD, associate professor of neuroscience; director of medical studies in neuroscience; and associate dean for curriculum in the School of Medicine’s Office of Education. Fortunately, many lectures were already available by video or podcast.

More disappointing and disruptive news came on March 16. Postponed procedures and the need to conserve PPE and limit the number of people at patients’ bedsides led Dean Brown and Richard Belitsky, MD, the Harold W. Jockers Associate Professor of Medical Education, associate professor of psychiatry, and deputy dean for education, to cancel clinical clerkships and electives, followed by nearly all subinternships on March 28. “Our ability to provide you with meaningful educational experiences during your clerkships has been eroded,” Brown wrote the students in an open letter.

“You can imagine the angst that the students are going through that need these [clerkships and subinternships] for graduate residency matching,” Schwartz said. Though the problem is nationwide, which led the Association of American Medical Colleges to discourage away rotations and recommend virtual interviews, that was small consolation, he said: “While the environment has changed for almost everybody, competing in it doesn’t make the student feel good.”

Under Schwartz’s leadership, faculty, students, and the Medical Education staff quickly created six new electives, particularly aimed at students whose rotations and subinternships were on hold. In one, students practiced management of acute disease processes through virtual case scenario simulation; another covered research methods, focusing on critically appraising literature about COVID-19, which often has not been peer reviewed. Two explored the pandemic through interdisciplinary lenses and two allowed students to rejoin clinical teams through telehealth.

While sheltering at home, students found additional ways beyond electives to help with the pandemic effort. Some helped in COVIDrelated clinical studies. Others assisted clinical teams by performing literature searches or calling patients for follow-up. In addition, many took it upon themselves to be as useful as possible to members of the New Haven community in need.

Second Look Weekend, Match Day celebrations, Medical Education Day, and Commencement were successfully moved online.

Reopening

On April 21, COVID-19 admissions peaked, with a census of 791 inpatients across the health system. On April 29, at last, more patients were being discharged than admitted. It was time to discuss reopening laboratories and childcare, resuming clinical trials and elective procedures, and bringing students back to the wards. Some clinical electives and subinternships resumed in late May, and clerkship clinical rotations resumed on July 6. Preclinical students made up for lost time with accelerated courses.

Some COVID-19-related changes are likely to become the new normal, such as telehealth.

“I don’t think the patients or the doctors want to go back” to mostly in-person visits, said outgoing urology chair Peter Schulam, MD, PhD, who spent much of the pandemic working on COVID-19 testing protocols in his role as chief innovation and transformation officer at YNHH (Schulam has since left Yale for a senior position at Johnson & Johnson). “This is the silver lining,” he said. “This may be the one good thing. The rapid adoption of telemedicine may improve the efficiency of our health care delivery.”

In the meantime, weary frontline providers were thinking about the next wave. “Phase two, scaling down to some unknown COVID plateau, on top of our usual hospital volume, is the current challenge. Preparing for the likelihood of recurrent surges in the future is the next challenge,” Tanoue said. “There’s this huge uncertainty. Where will the bottom [of the pandemic curve] be? Where will it settle out? Will there be recurrent surges? If so, how big will they be? We can try to plan ahead, but it is challenging with so much unknown.”

Desir said teams needed to be ready to “flex up” for that reason. He was part of discussions about how many people needed to be on infectious-disease or intensive-care teams. “We don’t quite know yet how big [these teams] should be, but I think we should be ready to serve as the referral center for Connecticut if we have another peak,” Desir said.

Meeting the COVID-19 challenge has brought out remarkable energy in doctors and nurses, Tanoue said. “It’s just amazing, how much people are willing to give, how committed they are to the mission.”

Zampano, who spent 16 years caring only for gynecologic oncology patients, staffed an end-of-life care unit for the first time during the pandemic, as well as a COVID-19 rapid evaluation clinic. The pandemic was awful, she said. “I’ve had my share of tears. I hope I never see another pandemic in my lifetime.”

But, she added, her glass is half full. “I’ve worked with some unbelievable people. The camaraderie that has come out of this and the ability to be flexible have been amazing!” Zampano said. “I wouldn’t consider myself a flexible person. I’m a nestbuilder. And I have flown out of my nest beyond anything I thought I would ever do.”

“I am pleased that we were able to do what we did—it was really extraordinary,” Desir said. “The entire system came together really quickly to make major, major changes. The idea of one team really came together.”