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MGH

Published On November 20, 2020

BASIC RESEARCH

Chapter 3: The Fight That Lies Ahead

When the caseload began to ease, clinicians came to grips with the new normal as researchers set their sights on ending the pandemic for good.

AFTER COVID-19 CASES in Massachusetts peaked at the end of April, they fell to a low by July and then rose moderately through the summer and fall. At MGH, this easing of the pandemic meant respite for exhausted workers throughout the hospital. But most understood that the drop in new infections merely marked a new phase, and that the fall and winter might well bring a second wave as the virus continued to spread through the rest of the country and around the world. There was an urgent need to develop better testing, more effective treatments and successful vaccines, research frontiers now being explored even more aggressively at MGH and the Ragon Institute. And while COVID-19 patients no longer overwhelmed the emergency department, the toll of delayed diagnosis and treatment throughout the hospital was another reckoning to be faced. 

The push to treat and contain COVID-19 had led, nationally, to the unintended neglect of other serious conditions. In March, as widespread stay-at-home orders took effect, people who needed care unrelated to the pandemic stayed away from hospitals in great numbers. U.S. emergency department visits declined by more than 40% during the early months of the pandemic, according to the CDC, and in the 10 weeks between March 15 and May 23, heart attack patients dropped by nearly a quarter and potential stroke victims dropped by a fifth, compared with the preceding 10 weeks. At MGH, similar patterns emerged. Patients needing treatment for stroke, heart attacks, appendicitis and brain hemorrhages were noticeably absent in April, says ED chair David Brown. “Our volume of acute medical emergencies dropped by 30%, but the incidence of those diseases didn’t drop,” Brown says. “People were waiting out those conditions at home because they were afraid of becoming infected. That’s the hidden morbidity and mortality of this epidemic—most of those people could have been treated and survived pre-COVID. But by delaying time-sensitive treatment, some people died. Others were more acutely ill when they finally came to the ED and died as a result of that.”

One area in which time is of the essence—cancer diagnosis and treatment—also experienced delays, as diagnostic procedures and surgery were postponed. That could lead to an as-yet-unmeasured rise in new or more advanced cancers, suggests Daniel Haber, director of the Mass General Cancer Center. Indeed, in a United Kingdom study that modeled the potential impact of medical service delays, deaths from breast, colorectal, esophageal and lung cancers in the five years after diagnosis were expected to increase by 5%. 

Addressing this backlog of care has become a priority at MGH and other hospitals. Yet even as the pandemic waned and with new precautions in place, many patients seemed reluctant to come back to the hospital or to local clinics. In the spring, MGH and other Boston medical centers came together with a television advertising campaign urging people not to delay care and emphasizing new safety measures. Since then, the ED and other parts of the hospital have seen the return of a more normal mix of patients. 

This is an issue that will certainly reemerge, however, if there is a second COVID-19 wave. “Last winter, we cleared the decks and shut down much of our routine operations,” says Inga T. Lennes, senior vice president of Practice Improvement and Patient Experience. “But if we’re in the same position again, we know we won’t want patients to put off urgent medical care, and we won’t shut down as much as we did before.” Still, she adds, “we know so much more about treating COVID-19 now. We’ll call on what we’ve learned to innovate in a more complex environment.”

Source: Israel Vargas: Contains Photos by Getty Images

ONE WAY TO AVOID shutting down doctor-patient visits even at the height of an infectious disease outbreak is to make those connections happen virtually, and the widespread adoption of telemedicine during the COVID-19 crisis has led to a range of tantalizing possibilities, most of which have already been battle tested. “In eight weeks, Mass General Brigham went from having 400 physicians who regularly used telemedicine to 11,000 providers who needed to be enabled," says neurologist Lee Schwamm, director of the Center for TeleHealth at MGH and vice president of Digital Health Virtual Care at Mass General Brigham. "Volume went from 0.2% of ambulatory care delivered virtually to 62%, which translated to some 200,000 visits per month.” 

The advent of “virtual video intercoms” could have a lasting impact, letting patients see and speak with clinicians outside their rooms and often far from the hospital. As COVID-19 cases rose and infection risks multiplied, clinicians began to use tablet computers mounted on IV poles. These devices, equipped with auto-answering software, provided a technological link to nurses and physicians who didn’t have to wear masks and shields. “It’s very frightening and impersonal for patients to only see providers covered in PPE,” Schwamm says. In addition to conserving PPE, virtual connections by video led to warmer, less rushed interactions, and also enabled remote monitoring of patients who may have been sleeping, sedated or confused. More than 1,500 of these intercom setups had been deployed at Mass General Brigham hospitals by the end of April, and that equipment stands ready to be moved back into patient rooms if there’s a new surge of COVID-19 cases.

Other innovations have included “virtual rounds,” in which clinicians in multiple locations can look in on patients and provide consultations—of particular value in treating complex COVID-19 cases, where there are few simple answers about the most effective therapy. And in some specialties, telemedicine has had a particularly profound impact. In hematology and oncology, for example, few specialists saw patients in virtual visits before the pandemic, says David Ryan, chief of Hematology/Oncology at MGH. But by the fall, 30% of oncology visits and 80% of initial outpatient hematology consultations were still happening via telemedicine. 

“This has opened the way to major changes in how cancer care will be delivered from now on,” Haber says. Many “surveillance” visits, in which oncologists and hematologists review scans and lab results, can now be conducted remotely, and providers can check in with patients virtually before and after chemotherapy sessions. “And many patients who normally would have to drive to Boston for those sessions and to see their oncologist now can choose virtual visits and go to a Mass General Brigham satellite near them for their treatments,” Ryan says. “This erases geographic boundaries,” adds Haber, who notes that telemedicine is extending the reach of MGH across the country by offering virtual consults with its specialists. 

Schwamm estimates that up to 30% of ambulatory visits will remain virtual even when there are no restrictions on patients coming to hospital clinics. The cost and logistical complications of traveling to a doctor’s office can be high, especially for patients who live far away or have conditions that make it hard to leave home. And in some cases virtual care may be better care, offering doctors a view of their patients that wasn’t possible before. “A video visit with a patient at home may provide important clues about why that person isn’t doing well, and family members can be there to answer questions,” Schwamm says. Virtual visits also make it easy for patients who have returned to a distant home after a hospital stay to continue to see MGH specialists, which can be important for continuity of care. “Physicians who once told me that telemedicine would never work for them now understand how much of a benefit it can be and how big a role it will play in their practices,” Schwamm says.

Still, not every patient is set up for telemedicine, and the next step is to make virtual care accessible to those who don’t have broadband internet, are visually impaired or have limited English. “Finding ways to deliver care virtually to patients who don’t have or can’t use existing technology is an intense area of focus for us,” Schwamm says.

RESEARCH AT MGH EXPLORING possible COVID-19 treatments continued through the spring and summer. In October, The New England Journal of Medicine published final trial results for the antiviral remdesivir showing that the drug cut recovery time by nearly one-third and also reduced the length of the initial hospital stay. While preliminary results from a larger international trial cast doubt on its effectiveness, the FDA in October granted full approval for the drug.

By August, however, the number of hospitalized patients at MGH who were eligible for COVID-19 trials had dwindled to the single digits, and participation in many studies—which needed those patients as test subjects—had slowed. One such trial was investigating a monoclonal antibody, LY-CoV555, that was derived from the blood of a recovered COVID-19 patient during the March outbreak in Washington state. In early June, MGH was one of several sites for a phase 1 safety trial of the drug being developed by drugmaker Eli Lilly. Following expanded testing at other sites, Lilly released data in September showing that the medication had helped improve the elimination of the virus that causes COVID-19 and may have reduced the rate of hospitalizations. 

Other treatments failed to live up to expectations. A study published in October found that tocilizumab—which lead investigators at MGH thought might ease the "cytokine storm" that can prove deadly in COVID-19 patients—in fact didn't reduce the need for breathing assistance or prevent deaths.

In the meantime, with a possible resurgence looming, Keith Flaherty, director of Clinical Research at the Mass General Cancer Center and leader of the COVID-19 clinical trials platform, says that he and his colleagues have six new treatment trials ready to launch. They are also prepared for additional studies of possible vaccines. 

But researchers have shifted some of their efforts to basic science, with work in the lab probing questions that include one of COVID-19’s biggest mysteries—why some people who are infected get severely ill while others have mild symptoms or none at all. Age, underlying health conditions and genetics play a role in deadly complications, but how they do so remains unexplained. In one of the largest basic research efforts to date, Nir Hacohen, director of the MGH Center for Cancer Immunology, is co-leading a 30-person team conducting molecular analyses of COVID-19 blood proteins, blood cells and antibodies. That work is providing a high-resolution look inside human immune cells as a way to find what separates infected patients who manage to shrug off the disease from those who become extremely ill. “We’re working to identify underlying cellular molecular causes of good and bad outcomes,” Hacohen says. 

Discovering genetic signatures associated with COVID-19 susceptibility could lead to drugs or combination therapies targeting specific kinds of cells in the blood, for example. This kind of precision medicine is a hallmark of cancer research, and COVID-19 studies could learn from the groundwork cancer has covered. Many cancer clinical trials now include multiple treatment arms or “baskets” that can help gauge the response to a range of drugs by patients with different genetic mutations or locations of cancer in their bodies. Flaherty, who has been a pioneer of such “adaptive” trials, now wants to do something similar with COVID-19 patients, testing whether particular treatments work in those who share specific genetic or nongenetic biomarkers. 

Source: Israel Vargas: Contains Photos by MGH Photography and Getty Images

BY SUMMER'S END, MANY disrupted, non-COVID-19 clinical trials at the Massachusetts General Research Institute were back on track, and new ones were actively recruiting patients, says Maurizio Fava, MGRI director of the Division of Clinical Research. But many protocols were different. Often, trial subjects were recruited virtually, and rather than being required to show up at the hospital for testing, procedures and data collection, patients in many cases were able to have home visits with nurses. Many of these changes, which may save time and money while promoting safety, could become permanent, Fava says.

In several other areas, too, alterations made during the pandemic are being embraced as better ways to do things even during more normal times. “We're working to pilot a continued palliative care presence in the Emergency Department, for example,” says Vicki Jackson, chief of Palliative Care and Geriatrics. And in the ICU, determining which patients would benefit from extracorporeal membrane oxygenation (ECMO) will still be made by a group of at least four ECMO experts, rather than giving a single physician the responsibility of what is often a life-or-death decision, according to Yuval Raz, medical director of Respiratory ECMO.

If fall or winter leads to a second surge of COVID-19 patients at MGH, materials management head Ed Raeke, charged with having sufficient supplies on hand, will be prepared. The hospital is currently supplied with a four-month cache that includes more than 600 items, which in addition to PPE includes disposable thermometers, stethoscopes and arterial blood gas syringes. 

“Every department has been asked to come up with a plan to manage a variety of future COVID scenarios,” says David Brown. “So we’ll be ready for whatever happens.” 

On September 25, the research team team of Dan Barouch, of Beth Israel Deaconess Hospital and the Ragon Institute, published results from the human trials of their vaccine effort that started the day the coronavirus genome was made public. Nearly 100% of the subjects had an immune response with only mild to moderate side effects, and of the vaccines to reach phase 3 trials, it is the first that could require only one dose. Barouch's team plans to enroll more than 60,000 volunteers, and some may come from the MGH satellite clinic in Chelsea, which is encouraging community members not only to get involved in vaccine trials but to get vaccines once the FDA has approved them. 

This approach—research working hand-in-hand with clinicians and community efforts—will continue to be a cornerstone of the hospital's response. As cases rise nationally, everyone at MGH will continue to look for answers, remain prepared and hope. 

READ CHAPTER 1

READ CHAPTER 2

DOSSIER

The Art of Oncology: COVID-19 Era,” Kerry Reynolds et al., The Oncologist, July 2020. An essay from nine staffers of the Mass General Cancer Center walks through the emotional and logistical difficulties of shifting focus during the COVID-19 surge.

A Digital Embrace to Blunt the Curve of COVID19 Pandemic,” by Lee Schwamm et al., npj Digital Medicine, May 2020. The overview of virtual care innovations at MGH during the surge points to possibilities for enduring change in digital medicine.

The Disproportionate Impact of Covid-19 on Communities of Color,” by Thomas D. Sequist, NEJM Catalyst, July 2020. The chief patient experience and equity officer at Mass General Brigham explores how racism caused poor pandemic outcomes.