All Hands On Deck

At the end of March, George Hripcsak, MD, had expected to attend a symposium in England for a global interdisciplinary research collaborative whose coordinating center operates out of VP&S. Instead, on March 26, Hripcsak and fellow members of the leadership committee of the Observational Health Data Sciences and Informatics (or OHDSI, pronounced “Odyssey”) launched an 88-hour virtual study-a-thon with more than 300 investigators from dozens of countries in attendance.

“This is how we shifted our efforts to COVID,” says Hripcsak, co-PI of the international OHDSI, “an around-the-clock, four-day meeting of researchers from North America, Europe, and Asia, coming together to kick off our COVID study.”

Since 2014, Hripcsak and other volunteer members of OHDSI have amassed a database of electronic health records and claims data on nearly 600 million patients worldwide. That dataset put them in a unique position to combine efforts against the new disease. With real-world data at their fingertips, they developed an observational study designed to answer questions about this novel illness, for example, Who is getting the disease more often? Which therapies work? What are the myriad risks for complications?

“There wasn’t a lot of sleep during those 88 hours,” says Hripcsak, but those sleepless nights yielded quick results. By early April, the use of hydroxychloroquine alone or in combination with azithromycin was under consideration as prophylaxis for health care workers. Hripcsak and colleagues alerted the U.S. Food and Drug Administration and its European counterpart—the European Medicines Agency—that the OHDSI database shows a number of sudden deaths were associated with short-course hydroxychloroquine/azithromycin among patients without COVID-19. Ultimately, government officials did not recommend this form of prophylaxis.

In parallel with the OHDSI work, Hripcsak published other COVID-related papers between April and June, including a study run by VP&S medical students and published in the British Medical Journal that characterized the course of disease of the first 1,000 COVID-19 patients admitted to NewYork-Presbyterian Hospital and a study published in the New England Journal of Medicine, written with Joshua Geleris, MD, and Neil Schluger, MD, demonstrating that hydroxychloroquine was ineffective at mitigating the risk of intubation and death among patients with COVID-19. 

Hripcsak was one of dozens of VP&S faculty who leveraged ongoing work to briskly and substantively address clinical and investigative challenges that emerged as New York City became the epicenter of the pandemic starting in March 2020.

At the Center for Radiological Research, director David Brenner, PhD, had been working on a particular wavelength region of UV light (far-UVC, 222 nm) which he had shown was efficient at killing airborne influenza virus but, unlike conventional germicidal UVC light, was safe for direct human exposure. He quickly pivoted his focus to SARS-CoV-2, the coronavirus that causes COVID-19. In a paper published in June, Brenner showed that far-UVC light, used within current regulatory safety limits, inactivated 90% of airborne coronaviruses in eight minutes and 99.9% within about 25 minutes.

“Based on our results, far-UVC light from overhead lights could be safely used to markedly reduce the ambient level of SARS-CoV-2 virus in occupied indoor spaces,” says Brenner. Unlike conventional germicidal UVC light, far-UVC light is safe for human exposure and has the potential to become as necessary as other precautions people take indoors. “Far-UVC light has great potential as a third approach, in addition to face masks and social distancing, to limit the transmission of SARS-CoV-2 and other viruses in occupied indoor spaces.”

Eric Greene, PhD, professor of biochemistry & molecular biophysics, found a way to support the pandemic response after suddenly finding himself working from home, writing papers and grants that were already in the pipeline. The Greene Lab was shut down in mid-March as Columbia and New York sought to “flatten the curve,” but Greene wanted to help, especially with so many of his Columbia colleagues on the front lines. “The worst thing in the world is to have a scientist stuck at home with nothing to do,” says Greene. “I started asking folks how I could help and found many people who were trying to figure out the same thing. Quickly—within the first week—we coalesced. That’s what really made things work.”

Through the VP&S grapevine, Greene learned about an emerging grassroots effort among VP&S researchers. Dubbed CRAC—Columbia Researchers Against COVID-19—the collective enterprise was launched by postdocs who realigned their research goals toward the pandemic after their labs were shut down.  Greene and Kenneth Olive, PhD, associate professor of medicine who conducts pancreatic cancer research, became CRAC faculty advisers. “I suggested that one of the things we should do is build a Columbia-wide database, listing everybody who is working on COVID-19-related topics and specify what it is they do, just as a way to communicate with one another,” Greene says.

In the early phases, Greene gathered names ad hoc, then learned that Andrea Califano, PhD, chair of the Department of Systems Biology, was doing the same. They collated their lists, and the database was taken over by the CRAC team, led by postdoc Haotian “Howie” Wu, PhD.

This effort led to a bigger, more far-reaching project: the COVID-19 Virtual Symposia, a live, weekly online lecture series featuring eight to 10 presenters each week from Columbia and around the globe, who relay the most current science on COVID-19. “It was a way to bring people together at the university,” says Greene, “and keep everyone up to date on the latest understanding of the disease.”

The Virtual Symposia series is hosted by Greene, Califano, Andrew Marks, MD, the Clyde’56 and Helen Wu Professor of Molecular Cardiology and chair of the Department of Physiology & Cellular Biophysics, and Stephen Goff, PhD, the Higgins Professor of Microbiology & Immunology and Biochemistry & Molecular Biophysics. “The symposium,” Greene adds, “would not have been possible without the truly amazing efforts of the CRAC team volunteers like postdocs Ester Cynn, Jessie Brown, and many others who run all of the behind the scenes operations. I really cannot overstate the importance of these volunteers to the overall effort.”

The inaugural symposium on Zoom was held April 1 with more than 700 Columbia scientists and clinicians in attendance. During the series, speakers reported on knowledge gleaned from the front lines in Italy, China, and Spain; others provided the latest on vaccine development and treatments; others offered commentary on evolving social issues related to the disease.  Greene says much of the information was generously presented before publication. “People were very willing to share data,” he says. “It was amazing to see.” Within the first three months, VP&S hosted 13 sessions of the COVID-19 Virtual Symposia, with about 200 attendees per session.

A month into the pandemic, as the virtual symposia launched, clinicians at NYP-Morgan Stanley Children’s Hospital noticed a cluster of previously healthy children presenting with multiple and sometimes critical symptoms; the condition would come to be known as multisystem inflammatory syndrome in children, or MIS-C. “We had to rapidly recognize, investigate, and treat a whole new syndrome affecting children related to COVID-19 that very few people in the world knew anything about,” says pediatric critical care physician and cardiologist Eva Cheung, MD.

Although MIS-C shared many features with Kawasaki’s disease (KD) and toxic shock syndrome (TSS), Cheung says, these novel cases were occurring at a higher rate than expected, so doctors suspected something new was emerging. “On average, we see a child with KD or TSS every several months, or even less. Since we were admitting one child after another—and, at the peak of MIS-C, many children a day—it just didn’t align with those two diseases,” Cheung says. “We had a suspicion this was connected to COVID-19.”

Cheung characterized MIS-C in a case series published in JAMA in June. She reported that the main sign of the syndrome was fever accompanied by other symptoms, such as gastrointestinal upset, nausea, vomiting, rash, and abnormal chest X-rays. Together, Cheung says, these complications illustrated that something about exposure to COVID-19 triggered an inflammatory reaction that made children sick.

Researchers believe MIS-C is rare; among the thousands of children receiving care at NYP, MIS-C was diagnosed in just 60, all of whom were treated at the hospital and have since gone home.  Cheung continues her research, prospectively monitoring this cohort for long-term effects of MIS-C. She also leads an ongoing study on the MIS-C treatment given at NYP, compared with other institutions during the surge, to help pinpoint the optimal protocol for managing the syndrome.

Like their colleagues in adult medicine, Cheung and her fellow MIS-C investigators were simultaneously responding to and documenting strategies to treat COVID-19 and its complications while also adjusting to abrupt transformations in where and how they saw patients. Pediatric cases in the NYP health care system—COVID and otherwise—were centralized at Morgan Stanley Children’s Hospital, where many pediatric specialists were also redeployed to care for adults. “Because children were less affected by COVID-19, we had capacity to take care of our city’s children and also open our doors to adult patients with COVID,” she explains. Other pediatric specialists were transferred to adult hospitals to contribute to critical care efforts there. “I don’t think there was a clinician in this institution who didn’t have to find a different role during the pandemic.”

Reimagination was a common theme running through VP&S research programs during the pandemic’s peak in New York City. Led by Muredach Reilly, MBBCh, director of the Irving Institute for Clinical and Translational Research, researchers pivoted and accelerated a years-long project. Researchers in the Irving Institute, the Institute for Genomic Medicine, and the Department of Pathology & Cell Biology with multiple other partners at the medical center, including the Office for Research, joined forces to launch an institutional biobank sooner than planned and with a changed focus. “We were planning on going live, enrolling all patients who consented at CUIMC as of April 1 then proactively collecting samples,” says Reilly. “But when COVID happened, we quickly pivoted our focus to enroll patients who tested positive for COVID at NYP/Columbia and preserve residual samples once the clinical laboratory had finished with the samples.” The most common sample collected was serum, but others were also collected: plasma, nasal pharyngeal swabs, urine, feces, cerebral spinal fluid, and the concentrated white blood cell product known as “buffy coats,” which is used for DNA extraction.

“Patients were very interested in contributing and participating in this effort,” says Jennifer Williamson, MS, MPH, associate vice dean for research policy and scientific strategy, who worked with Reilly and other faculty to launch the biobank and oversee outreach to patients. The willingness of patients to help immediately made the biobank useful for COVID-19 and MIS-C research. “While other institutions said it could take up to five years before a newly established biorepository would make an impact, researchers were using our samples just four months after the biobank began,” Williamson adds.

By the end of June, about 7,000 current and former patients with COVID had agreed to the use of their samples—approximately 70,000 total samples had been collected, including one of the largest sets of longitudinal MIS-C samples in the country—in research. Almost 2,000 other patients have consented to ongoing involvement in the biobank and agreed to be contacted for other research studies.

“With samples from the biobank and electronic health records, we can provide patients with ongoing follow-up while also trying to answer important questions such as why some people get very sick and some don’t and why some people respond to some treatments and others don’t,” says Reilly.

Insights from the front lines of patient care have informed other areas of research, including women’s health. Cynthia Gyamfi-Bannerman, MD, a maternal-fetal medicine specialist, co-authored a research letter published in JAMA that revealed social determinants associated with an increased risk of infection—namely, a higher number of people living in a household, a more crowded household, and a lower socioeconomic status—among pregnant women delivering at two NYP hospitals between mid-March and mid-April. “One may think that because New York City is so dense, there’s little that can slow the spread of the virus, but our study suggests the risk of infection is related to household, rather than urban, density,” says Gyamfi-Bannerman.

Jeremy Beitler, MD, a pulmonary intensivist and director of clinical research for the Center for Acute Respiratory Failure, developed, implemented, and published a ventilator-sharing protocol as a public health preparedness tactic to mitigate anticipated ventilator shortages at the height of the epidemic. Through thorough review and pairing of compatible patients, these breathing machines were successfully used to support two people at the same time for two days. Results from the initial series of patients were published in the American Journal of Respiratory and Critical Care Medicine, and the protocol has been adopted by hospitals around the globe. “We’re doing something that hasn’t really ever been done before, but now is the time to do it,” Beitler told the New York Times.

The successful pivot to COVID-19 research during the height of the pandemic was borne out of a shared sense of purpose and unity across departments, say researchers. “We have learned to work with our colleagues in a way that we really didn’t ever need to in the past,” says Cheung. “Health care for adults and children are very separate—separate buildings, separate hospitals. But everyone adjusted their practice and cared for so many patients in so many different locations. It was an incredible demonstration of teamwork.”

Greene shares the same sentiment from the bench. “It has been remarkable to see how many labs have coalesced to attack the problem—both at Columbia and worldwide. I’ve gotten to know so many people I would have never had the opportunity to interact with before, which has been valuable.”

The collaborations formed through a shared commitment to fighting COVID-19 are likely to endure beyond the end of the pandemic. As Williamson puts it: “Whenever you’re working on something that is so important, everyone clearly knows the mission and focuses on making it work, it is incredibly rewarding. It’s the best part of Columbia.”

This article was originally published in the 2020 VP&S Annual Report.