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MGH

Published On November 20, 2020

BASIC RESEARCH

Chapter 2: The Virtues of Necessity

As the first COVID-19 patients arrived, pressure mounted to discover how the disease worked and how it could be beaten back.

AFTER THE FIRST COVID-19 cases from the Biogen conference arrived in the MGH Emergency Department, normal operations quickly came to a halt. Hundreds of infected patients soon flooded in, many struggling to catch their next breath. “We were seeing a relentless tide of critically ill COVID patients in respiratory failure,” says David Brown, chair of the Department of Emergency Medicine. Where the ED might normally see two patients a day with lungs deteriorated enough to require a ventilator, physicians there were soon using the machines on some 20 patients a day. 

Brown and the 480 clinicians in his department were the first to encounter this surge, and even as they sought to help frightened people suffering from a poorly understood new disease, Brown and his team also had to consider their own safety. “At the start, we weren’t sure how transmissible COVID was, how dangerous it was to providers or whether our PPE would work,” he says. “We’re all used to taking care of horrendous injuries and devastating illnesses in emergency medicine. But that care doesn’t normally endanger ourselves or our families.” 

Brown assumed he would soon be infected, and to avoid passing along the virus to his wife and adult children, one of whom was pregnant, he moved out of his home and into an apartment near the hospital. There he roused himself every day at 2 a.m., logged into the hospital system to see how many patients were in the ED and then called colleagues on the floor to find out how they were faring. At 5 a.m., he would check in again before heading to the hospital. His usual team had been swelled by orthopedists and other surgeons who, when elective procedures were sidelined by the crisis, had eagerly stepped forward to help. 

In the ED, physicians barely had time to issue medical orders for one patient before moving on to the next. But Brown made time to visit the ICUs and COVID-only floors to look in on patients. “My department saw only acutely ill patients gasping for air,” he says. “It was really important for staff morale to know that the vast majority of COVID patients at the hospital got better and went home.” 

Worse outcomes—protracted illness and death—were also in the cards, and preparing for those meant developing a deployment strategy for a team of palliative care physicians, whose goal was to understand a patient’s suffering and reduce it if they could. “We were there to get to know them and understand their goals, to hold and support them and to be a conduit to families,” says Vicki Jackson, chief of Palliative Care and Geriatrics. One frequent task involved explaining to elderly patients what they could expect if they were intubated and admitted to the ICU—a job made especially challenging when dementia was involved. “They were confused, fearful and couldn’t be with someone they knew,” Jackson says. “It was so important for families to see that we were taking time to get to know their loved ones as we made our recommendations.” 

As infections in the Boston area multiplied, Inga T. Lennes, senior vice president of Practice Improvement and Patience Experience, oversaw the opening of three additional COVID-19 testing sites. At one, in the hospital’s sports medicine clinic two blocks away, an ambulance stood ready to take people to the ED. “Within hours of being referred for testing by their doctors, some patients’ conditions had rapidly deteriorated and we needed to get them in quickly,” Lennes says. “We used that ambulance every day.”

Meanwhile, a new kind of treatment area—a respiratory illness clinic, or RIC—was created. RICs serve as an intermediate step between testing and possible hospitalization. At the MGH testing sites, some patients with COVID-19 symptoms who were considered at high risk of getting very sick were sent immediately to one of the new RICs. There, doctors performed chest radiographs and checked oxygen saturation levels to gauge whether infections were progressing dangerously. Patients then might be directed to the ED or sent home to recover. By mid-April, clinicians in the RICs, which freed ED staff to concentrate on caring for those who were already critically ill, were examining about 320 patients a day. 

On April 5, the hospital had 201 COVID-19-positive patients, 82 of whom were in the ICUs. Infected patients ultimately filled 12 floors of the hospital, and the hospitalists—specialists who attend to hospitalized patients—and medical residents were stretched thin trying to take care of so many seriously ill people. So doctors from other specialties pitched in, and on COVID floors, a patient might be attended by a radiologist, a neurologist, a gastroenterologist, a general internist or a pediatrician. “At the peak, we had 30 teams taking care of COVID patients and only one-third of those were hospitalists and residents,” says Amber Moore, a hospitalist who led the deployment of physicians for COVID-19 patients. It was just one more example of the “all hands on deck” ethos that now prevailed throughout the hospital.

Source: Israel Vargas: Contains Photos by Getty Images

THOUGH MUCH OF MGH was transformed to respond to the crisis, there was no guarantee that the pandemic wouldn’t overwhelm every hospital in the Boston area. On March 31, retired Brigadier General John “Jack” Hammond got an urgent phone call from Massachusetts Gov. Charlie Baker asking whether he would oversee construction and management of a field hospital—1,000 new beds inside the Boston Convention and Exhibition Center equipped to host an overflow of post-acute COVID-19 patients. And also … could he get it built in a week?

Hammond is director of Home Base, a program run by the Red Sox Foundation and MGH for war veterans with mental health conditions and brain injuries. During his decades in the military, he led expeditionary missions in Afghanistan, Iraq and the United States. But this felt even more daunting. “In the Army, I learned that you can do pretty much anything as long as you have the right people and the right stuff,” Hammond says. “In the beginning, we didn’t have any people or any stuff.” 

The field hospital, to be called Boston Hope, would be reserved for patients who no longer needed acute care but who were too sick to go home or were still infectious. Boston Hope would also provide treatment for members of the city’s homeless population who tested positive for the coronavirus.  

Hammond quickly assembled a leadership team, which included Michael Allard, chief operating officer for Home Base, Jeanette Ives Erickson, chief nurse emerita at MGH, who agreed to co-direct clinical care and operations, and Giles Boland, president of the Brigham and Women’s Physician's Organization. On April 1, the new team met with Hammond at the 516,000-square-foot convention center.  Soon, construction crews were working around the clock, and in less than a week they had built and equipped all 1,000 patient rooms, including a six-bed rapid response unit for those whose conditions unexpectedly worsened. “Our goal was to deliver post-acute care, but when these patients crash, they crash quickly,” Hammond says.

Clinicians from Mass General Brigham—a health system that includes MGH, Brigham and Women’s and other area hospitals—volunteered to work shifts at the new facility,  and many others came from the large pool of doctors, nurses and other health workers who had been furloughed from local hospitals and clinics during the pandemic. The U.S. Army Reserve sent an 80-person team to pitch in. More than 1,000 people ultimately worked shifts at Boston Hope, and they treated more than 700 patients during the nearly two months it was in operation. 

WHEREVER COVID-10 SPREAD, physicians and nurses labored at a constant disadvantage, handicapped by a lack of knowledge about the new virus and what therapies might be effective against it. Those became the most pressing scientific questions of the decade, and to fill that knowledge gap, hundreds of COVID-19 research trials were launched around the world. The Mass General Research Institute was inundated by proposals from academic researchers looking to put their ideas into practice at the hospital. “Everybody wanted to do a trial at MGH,” says Maurizio Fava, chief of the Department of Psychiatry and director of the Division of Clinical Research of the MGRI. 

On March 20, most non-COVID-19 research at MGRI was put on hold, and many of the scientists and physicians who had been working on other studies shifted to COVID-19, aiding a wide range of efforts to find vaccines and treatments. 

These first clinical trials sponsored by the hospital were led by Lorenzo Berra, an anesthesiologist and medical director for respiratory care. Italian by birth and educated in Milan, Berra had heard from family members and colleagues about COVID-19’s devastating impact in Italy. Many severe cases there led to a life-threatening lung condition called acute respiratory distress syndrome, or ARDS. Nitric oxide, which can improve lung oxygenation, is a Food and Drug Administration–approved treatment for ARDS, and studies during previous coronavirus outbreaks suggested that the inhaled gas has a virus-killing effect. In late March, the hospital began testing inhaled nitric oxide. Berra is leading three multicenter trials sponsored by MGH: one using the gas with very sick patients, another for those with mild to moderate symptoms and a third testing whether it can protect health care workers. 

Clinical trials of another possible treatment, remdesivir, were already underway in China, and in late February, the National Institute of Allergy and Infectious Diseases (NIAID) announced it was spearheading a test of the antiviral, which had been used during the 2018 Ebola outbreak in the Democratic Republic of Congo. MGH became the first site in New England to take part in the NIAID trial. Enrolled patients, who had COVID-19 and were experiencing lower respiratory tract infections, were randomized into treatment and placebo groups. 

But as the hospital began recruiting patients for this and other trials, things were becoming chaotic on COVID-only patient floors. Nurses were already hard pressed to take care of so many sick and infectious patients, and now they also had to keep track of which ones were in what trials, each of which demanded a strict protocol. “It was clear we needed to organize a coordinated research response,” says Katrina Armstrong, physician in chief and chair of the Department of Medicine at MGH.

On March 24, Armstrong called Keith Flaherty, director of Clinical Research at the Mass General Cancer Center and a colleague for three decades. She asked him to help create a system that could keep abreast of all new COVID-19 trial proposals and coordinate the initial four trials already in motion. Over the next two days, Flaherty reached out by email to invite dozens of investigators to participate in an enterprise that would be overseen by three committees—a steering group, another devoted to scientific review and a third looking at trial implementation. “I didn’t know most of the people I contacted, but everybody said yes,” Flaherty says. “I don’t think they knew what they were getting into.” 

The steering committee inherited a deluge of proposals, with several more arriving every day. A randomized trial that would normally take a year or more to launch now needed to happen in weeks, even days. “We had to very quickly determine which studies might move the needle,” Flaherty says. During the pandemic’s first wave, the group seriously considered more than 100 proposals. 

Most didn’t make the grade, but one that did qualify was hydroxychloroquine, an antimalarial medication also used to treat lupus and rheumatoid arthritis. It was highly touted after several small studies in China and France suggested that it might help patients with COVID-19, and the FDA had issued emergency authorization to use the drug to treat hospitalized patients, despite known side effects that included heart irregularities and seizures. “It was a hot issue,” Flaherty says. 

Even as this study got started in mid-April, emerging research signaled that the drug might do more harm than good, and questions were raised about the validity of past studies. At MGH, only patients participating in the trial were given the drug, and in June the study was halted and the FDA emergency authorization withdrawn. 

Studies were also taking a fresh look at tocilizumab, also known as Actemra, a rheumatoid arthritis drug, and in mid-April, MGH led a study looking at its effects on COVID-19-related systemic inflammation. The treatment was designed to mitigate the body’s “cytokine storm,” an overzealous immune response observed in many COVID-19 patients that can lead to pneumonia, blood clots, organ failure and often death. Other area hospitals also began enrolling patients, and the study eventually included almost 250 patients. “Most were very sick and eager to participate,” says John Stone, director of Clinical Rheumatology at MGH and principal investigator in the trial. “We enrolled patients from early in the morning until late in the evening, and they typically received the drug within two hours of consent. Time was of the essence.” 

As these and other trials got under way, the trials network made changes to untangle the snarls they encountered in coordination and implementation. In early April, Flaherty appointed a team of three physicians to find and screen every COVID-19 patient for possible enrollment. “The teams organizing individual trials weren’t identifying anywhere near all of the infected patients,” says Michael Dougan, a gastroenterologist and immunotherapy researcher who was part of the team. “In this situation, if a COVID patient is in the hospital and isn’t offered a clinical trial, it’s a failure in standard of care. Our system was designed not just to prevent these trials from bumping into each other, but also to prevent people from being missed.”

Every morning, the team met to review patient medical records and generate a list of potential trial candidates. Team members had to consider an encyclopedic list of details governing each trial’s criteria for inclusion and exclusion. “Some required a positive COVID test within 48 hours, others within 14 days,” says Chana Sacks, an internist at MGH and another member of the team. “For one trial patients had to be intubated on a ventilator; for others, they couldn’t be.” Team members were in round-the-clock contact with trial researchers to let them know about possible new participants. 

Initially, there were more eligible patients than trial slots, but that quickly changed as more trials got up and running. From April 9 to July 9, the team screened more than 1,300 patients and referred as many as it could to trials involving antivirals, immune modulation, anticoagulants and several respiratory treatment strategies. 

The job of putting the trial protocols into practice—charting patient data, collecting blood or other biospecimens and administering treatments—fell to Kathryn Hall, nurse director for the Translational and Clinical Research Centers, and her team, including more than two dozen research nurses and nurse practitioners. Hall and her colleagues saw some trial patients recover, while others succumbed. “There was nothing else to offer these patients except the clinical trials, and we saw people holding on to hope that they were receiving a drug that would help them,” Hall says. “We didn’t know whether someone was receiving the drug or the placebo, and we watched many patients deteriorate quickly, in much larger numbers than we were used to. It was very distressing to all of the providers.”

At the end of April, early results from the remdesivir trials provided a sorely needed morale boost. The antiviral had helped some patients recover more quickly and appeared to improve survival as well. “The positive remdesivir results were a turning point,” Flaherty says. “I think many of us felt relieved that everything we were doing wasn’t futile.” 

Source: Israel Vargas: Contains Photos by MGH Photography

AS THE FIRST WAVE of COVID-19 patients began filling beds at MGH in March, chief resident Aisha James and several other physicians-in-training realized that language barriers could be an issue. In the early stage of the pandemic, a large percentage of patients came from four communities north of Boston that have large Spanish-speaking populations: Chelsea, East Boston, Everett and Revere. “There were so many more patients from these cities than the hospital was used to seeing,” James says. 

No community in Massachusetts had been hit harder than Chelsea, a densely populated city of 40,000 where about one in five residents lives below the poverty line. Multiple generations often share small apartments, where the virus spread through respiratory droplets.Almost 80% of employed Chelsea residents were also deemed essential workers during the pandemic, and most relied on public transportation to get to their jobs.  

All of those factors made Chelsea residents far more likely to be infected with COVID-19—and those who did get sick were also at increased risk for severe symptoms and complications. A large portion of residents have pre-existing conditions that include obesity, diabetes and heart disease, says Dean Xerras, medical director of MGH Chelsea HealthCare Center. The people of Chelsea, which is near Logan Airport and is clogged with heavy truck traffic, also have high rates of asthma and other respiratory illnesses.  And many there who developed symptoms of COVID-19 may have delayed seeking care out of fear they would lose jobs or, in the case of undocumented immigrants, be reported to federal authorities, Xerras says. That could explain why a significant portion of COVID-19 patients arriving from Chelsea and neighboring communities were so sick on arrival.  

As this data filtered up to the Hospital Incident Command System, it became clear that a coordinated effort in these neighborhoods would have to be a critical part of the hospital’s response. Joan Quinlan, vice president of Community Health at MGH, joined with Joseph Betancourt, vice president and chief equity and inclusion officer at MGH, to create the Mass General Equity and Community Health COVID Response Team. “These places are on fire,” Betancourt recalls thinking. “We had to figure out a way to stop the spread.” 

Betancourt, Quinlan and other MGH officials developed a plan. Their launch pad was the MGH Chelsea HealthCare Center, which had opened in 1971 and now serves 32,000 patients a year. Converting one of its four floors to a respiratory illness clinic, or RIC, meant that COVID-19 tests and evaluations of symptoms could be given daily to as many as 300 people from Chelsea and neighboring East Boston, Everett and Revere. Patients who visited the RIC also received “care kits,” which contained masks, hand sanitizer, cleaning materials and educational pamphlets in English and Spanish. Another 80,000 of the kits were handed out across the city. Radio spots in English and Spanish, as well as infographics for Instagram and Facebook, reinforced advice about mask wearing, social distancing and other protective measures. “If you can’t change people’s social conditions, at least you can mitigate spread by offering some basic tools,” Betancourt says.

The biggest puzzle in the MGH response was to find a way to help people in the community who had been diagnosed with COVID-19 but whose symptoms were mild. Because they were still contagious, they risked infecting family members or roommates if they went home. “We started to get particularly concerned when we heard that people who had tested positive were being summarily thrown out of their apartments by roommates,” says Chelsea City Manager Thomas Ambrosino. 

The solution was a bold plan, worked out with the help of municipal officials, that transformed a 147-room Quality Inn off Route 1 in Revere into an isolation center for those who had COVID-19 and nowhere else to go. MGH took responsibility for delivering medical care, which was overseen by Dean Xerras and registered nurse Jacky Nally, program manager for the MGH Center for Disaster Medicine. Under their guidance, the hotel lobby became a nursing station and an intake area. Hand-washing stations and areas for removing PPE were set up throughout the hotel, which was staffed with doctors, nurses, medical assistants, nurse practitioners and social workers. Nally tried to make sure that at least half  of the workers were multilingual.  

When the isolation center opened on April 16, a clinical team in full PPE was there to check on residents’ symptoms twice a day. “Sometimes we simply took their vital signs and asked a few questions to ensure that they were still improving,” Nally says. “Sometimes it involved a lot more than that.” Many patients had medical conditions other than COVID-19 that needed management. Social workers called patients twice daily to monitor their mental health.  

The isolation center closed on June 9 after caring for 153 adults, children and infants. “I think we absolutely slowed the transmission of the coronavirus,” Nally says. At the height of the spring surge, Chelsea recorded more than 80 new cases of COVID-19 per day, but that figure had dropped into the single digits by August, Ambrosino says. The percentage of people in Chelsea testing positive for the virus continues to be disproportionate, about three times as high as the state average at the end of October. “This is not over,” Xerras says. “It’s a marathon, not a sprint to the finish line.”

THE SENSE OF FIGHTING BACK, together, against an implacable foe animated the staff at the hospital during those months, which day to day involved long and grueling hours and a fear that everyone’s best efforts would not be enough. Sometimes an encouraging development would arise, as when it was reported that “proning”—rolling patients onto their stomachs—could ease the breathing and improve oxygenation of some COVID-19 patients on ventilators. But proning in practice turned out to be a delicate, complicated procedure, requiring six practitioners to turn a patient safely without dislodging the endotracheal tube or any of the other tubes, lines and drains. “If the procedure isn’t done precisely, proning can destabilize patients, causing them to have a severe and sustained drop in blood pressure, and some can develop cardiac arrhythmias,” says Robert Kacmarek, director of Respiratory Care at MGH.  

So the hospital created five specially trained proning teams, made up of 95 operating room nurses, operating room assistants and physical therapists. Each team is supported by the patient’s primary nurse and respiratory therapist. On April 9, the teams were deployed in MGH ICUs, led by Colleen Snydeman, executive director of nursing and patient care services in the Office of Quality, Safety and Practice. “I will never forget being greeted by the angels of the proning team—arriving en masse like the 82nd Airborne Division to expertly flip over intubated critically ill patients with hypoxemia,” says Walter O’Donnell, clinical director of the Pulmonary/Critical Care Unit.  

Another promising way to deliver more oxygen to patients on ventilators is extracorporeal membrane oxygenation (ECMO). Blood is pumped outside the body to a heart-lung machine that removes carbon dioxide and adds oxygen before sending the rewarmed blood back into the patient. ECMO gives the lungs a chance to rest and heal while antibiotics and other therapies do their work, and reports from China and Italy showed it was effective for some patients with COVID-19. But ECMO is by no means benign therapy; bleeding complications are common and can be fatal, and blood infections also occur. “Using ECMO on the wrong patients is harmful and will just prolong the dying process,” says Yuval Raz, medical director of Respiratory ECMO at MGH. 

Indeed, the dying process was a bitter constant. While death in a hospital is by no means a rare occurrence, the pandemic rules that limited exposure to the virus meant patients usually were alone in their last moments, far from family and even their caregivers. In more normal times, says Kerry Reynolds, clinical director of Inpatient Oncology Services, doctors would hold patients’ hands and take their time when they had to deliver bad news. “But we couldn’t do that with COVID patients,” Reynolds says. Face shields and masks could blunt the empathy in clinicians’ faces. “Patients having to be isolated was traumatic for all of us,” Reynolds says. Adds Kathryn Hibbert, director of the Medical Intensive Care Unit, “Watching patients, some of them young, die alone without family were the darkest, saddest times for me.” 

Beginning in March, however, the rules were changed to allow one or two family members to visit dying patients in a special unit at the hospital. Todd Rinehart, social work director for the Division of Palliative Care and Geriatric Medicine, collaborated with nursing leadership for that policy shift. With palliative care physician Kathleen Doyle and chaplain Sarah Byrne-Martelli, he created a program they called No One Dies Lonely, which found ways to connect absent loved ones with patients to say goodbye. Rinehart also organized, in coordination with primary care physician Kerri Palamara McGrath and others, a memorial service for MGH workers to honor patients who had died, an event at which cellist Yo-Yo Ma performed. 

Yet most patients survived, and every time one became well enough to leave the ICU, it was a vindication and a cause for hope. Staff members would line the hallways and cheer as another person they had helped through many difficult and desperate moments was wheeled out. “Seeing those successes helped keep everyone’s spirits up,” Hibbert says. Patients continued to leave the hospital, and on one day in April, a milestone was reached, with fewer than 100 patients on ventilators. On that day, 20 doctors, nurses and respiratory therapists had an impromptu celebration on a parking garage roof. “We were just so elated and relieved,” Hibbert says.

READ CHAPTER 3: THE FIGHT THAT LIES AHEAD

DOSSIER

Veno-venous Extracorporeal Membrane Oxygenation for Respiratory Failure in COVID-19 Patients,” by Asishana Osho et al., Annals of Surgery, May 2020. The piece outlines the use of ECMO as a life-saving therapy for COVID-19 patients.

The Experience of Emergency Department Providers With Embedded Palliative Care During COVID,” by Emily Aaronson et al., Journal of Pain Symptom Management, August 2020. Palliative care in the ED has particular value during a mass emergency event.

Improving Clinical Trial Enrollment – In the Covid-19 Era and Beyond,” by Crystal M. North et al., The New England Journal of Medicine, July 2020. The overview shows MGH's clinical trial strategy during the surge.