Through innovative research, medication management, open communication with colleagues and patients, and customized protocols, experts in the Johns Hopkins Comprehensive Transplant Center have worked doggedly throughout the pandemic to preserve the health of people who have received a transplant. Their efforts are paying off: Inpatient mortality rates have been under 5% at Johns Hopkins — far lower than the 20% or higher rates reported nationally.
“Big picture, we recognized the urgency of COVID and what we needed to do,” says Daniel Brennan, the center’s medical director. With similar infectious disease concerns such as West Nile virus and Zika, he says, patients undergoing transplants were particularly susceptible to disease and complications due to their immunosuppressed states.
The team’s multidisciplinary professionals care for a roster of over 5,500 solid organ transplant recipients, says Willa Cochran, an infectious disease nurse practitioner with the center.
The Transplant Teams’ Approach When COVID Struck
When the virus that causes COVID-19 hit in March 2020, Brennan instituted a daily video call to discuss strategies with the transplant nurse coordinators, Cochran, the transplant physicians on service, and transplant center administrator Jaclyn Bannon. One approach was to adjust medication regimens: lessening or halting the drug mycophenolate, which also lowers immune system white blood cells; maintaining tacrolimus, a drug to prevent organ rejection, because of its antiviral activity; and adding vitamin D and aspirin.
Under Bannon’s direction, the team sent pulse oximeters to patients’ homes to monitor oxygen levels in the blood, and instructed patients to come to the hospital or emergency department if levels dropped below 93%. Additionally, they took advantage of access to newer drugs as they emerged, such as remdesivir and convalescent plasma for inpatients — referring less-sick patients reporting COVID-19 symptoms to the Baltimore Convention Center Field Hospital for outpatient treatment with monoclonal antibodies.
The group also moved clinic visits from in-person to telehealth appointments, and used a blood test to study circulating cell-free DNA from donor organs that could indicate organ rejection, sparing many kidney and lung transplant recipients from invasive biopsies.
Nurse Coordinators and Their Crucial Role in Saving Lives
Much credit goes to nurse coordinators, who addressed concerns for each patient with surgeons, infectious disease physicians and others, says Cochran: “They were working on the ground to save lives long before the emergency room, long before the ICU, long before the intubation — by telephone calls to patients’ homes.”
As COVID-19 vaccines became available, transplant center staff members sent messages to all recipients and to those on the waitlist to stress the importance of vaccination. Additionally, the team encouraged early use of certain monoclonal antibodies for outpatient treatment. In this nurse- and nurse practitioner-driven initiative (initially bamlanivimab and casirivimab/imdevimab, then more recently sotrovimab during the omicron surge), teams worked with colleagues at the Baltimore Convention Center Field Hospital, Johns Hopkins Home Care Group and other agencies, who worked tirelessly to make these products available. The treatments “undoubtedly saved many lives and prevented many hospitalizations,” says transplant infectious disease physician Robin Avery, one of eight such experts involved.
The Trials of the Omicron Surge
The omicron variant that emerged in late November 2021 was “by far the biggest challenge of our personal and professional lives,” Cochran says. While vaccines help somewhat, transplant recipients achieve far less immunity against the virus than the general population. Between March 2020 and June 2021, the team managed around 600 cases of COVID-19 among their patients. Starting late December 2021, they saw as many as 35 new COVID cases a day.
With early access to sotrovimab, a monoclonal antibody that demonstrated effectiveness against omicron, the multidisciplinary team screened new cases daily to identify those who would most benefit from the treatment. When Evusheld, a preventive combination monoclonal antibody against omicron, became available, infectious disease physician Bill Werbel and others developed a tiered system for the limited supply based on risk, starting with lung transplant recipients who had no antibody response to vaccines. For the most part, Brennan says, the team kept patients out of the hospital.
Since the start of the omicron surge, some team members awaken as early as 3:30 a.m. to review treatments and literature reports, respond to messages from patients and contribute to ongoing research studies. To date, team members have counseled hundreds of anxious immunocompromised individuals by phone or email, both Johns Hopkins patients as well as others with no connection to Johns Hopkins who found their contact information.
Monitoring emerging treatments and medications has been an ongoing process for the transplant team. For example, paxlovid, an oral antiviral medication for COVID-19, was considered an exciting advance for the treatment of COVID in outpatients. But there is a potentially dangerous drug-drug interaction between paxlovid and certain immunosuppressive drugs, including tacrolimus, so Brennan and other team members educated the Johns Hopkins community and other clinicians not to give it to transplant recipients.
Helping Guide the Public Through Scientific Research
Throughout, researchers have been publishing their work so other centers can benefit and preparing patient guides to cover safe living during the pandemic. The Johns Hopkins Epidemiology Research Group in Organ Transplantation — under the direction of transplant surgeon and epidemiologist Dorry Segev — has led the field in characterizing suboptimal COVID vaccine responses in transplant recipients in a nationwide observational vaccine study involving thousands of transplant recipients, and has called for more studies involving people who are immunocompromised. Building on this foundation, ongoing NIH-funded clinical trials led by infectious disease physicians Christine Durand and Werbel are exploring novel ways to enhance vaccine responses in this vulnerable population.
“We are not going to rest until we get everyone protected, or until the pandemic ends,” Avery says. “So many immunocompromised people have remained completely isolated for the entire pandemic, and have had to put their lives on hold. I am encouraged that we now have more effective treatments to offer them, but we still are not yet at the point where we know enough about what constitutes protection that we can counsel people to relax their safety precautions.”
For more information, visit the Johns Hopkins Transplant Center website.