Judith A. Aberg, MD, is the principal investigator of multiple COVID-19 prevention and treatment trials at the Mount Sinai Health System.
“I did not anticipate how difficult it was—both for me and for the people who were turning to me for answers—to hear myself saying, ‘I just don’t know’ as often as I did during the early days of the pandemic.” Insights like this, and a look at the progress of COVID-19 vaccines, are offered by Judith A. Aberg, MD, a central figure in the Mount Sinai Health System’s pandemic response. Dr. Aberg, the Dr. George Baehr Professor of Clinical Medicine at the Icahn School of Medicine at Mount Sinai, is principal investigator of multiple COVID-19 prevention and treatment trials.
What was your most challenging day during the pandemic?
During the peak of the pandemic, there were so many challenging days and sleepless nights that it is difficult to choose just one! There were challenges, but there were also so many times that I felt pride in my own Infectious Diseases (ID) and Infection Prevention faculty and also in all the amazing triumphs occurring throughout the Mount Sinai Health System. We had so little knowledge about this disease and so few therapies to offer patients, yet there was the expectation that ID would have the answers.
As Chief, I needed to gather and disseminate the best available evidence, whether from our own observations, from preprint research or press releases, or from discussions with colleagues across the globe, in order to maintain the ID Division’s optimism and confidence in our recommendations. I have always been comfortable acknowledging the limitations of my own knowledge, but I did not anticipate how difficult it was—both for me and for the people who were turning to me for answers—to hear myself saying, “I just don’t know” as often as I did during the early days of the pandemic.
Nevertheless, we proceeded with the development of system-wide treatment guidelines based on best available evidence at the time, which would be frequently revised as more data became available. I am also proud that, despite the considerable clinical burden that COVID-19 placed on ID, we immediately launched into clinical trials and emergency use of investigational therapeutics. I am an experienced clinical trialist, but many of my faculty and our trainees are not. We all had to learn how to consent patients or their family members remotely, which is unprecedented in my experience, but necessary because family were not allowed to visit in person, and often they themselves were in quarantine. It was heartbreaking, listening to their stories and knowing that I had no answers or even the words to alleviate their fear and sadness.
At times, tensions ran high; it seemed as though everyone wanted their loved one to get whatever latest therapy was in the news. I received frequent calls and e-mails from patients’ family and friends, all advocating for their loved one to receive a potential therapy, regardless of limited supplies or use restrictions. It was a fine line, having to remind desperate families that every sick person is somebody to someone, while still maintaining compassion for their specific, personal grief. There were many nights when I would come home past midnight and sit with my laptop and phone, answering requests for help with what I hoped was reassurance and support, despite having no proven therapies to offer. Each patient lost was a tragedy, but the seemingly constant despair, particularly of those whose loved ones were rapidly worsening toward needing mechanical ventilators, was cumulatively overwhelming.
We were all just learning this disease, and yet therapeutic decisions still had to be made—so that is what I did. We have learned so much more now, even that some of our choices were not helpful, if not outright wrong. But at the time, we could only do what we thought was best.
How did the COVID-19 response affect you personally?
Like many, I have lost all semblance of balance between my work and personal life. And like many, I have lost colleagues and friends to the wrath of COVID-19. My ID faculty and staff know me as a person who is always on top of everything and available for them, but I have had to learn to let go and to accept that I just cannot do everything that I would like to. Since February, COVID has consumed almost every waking moment. I have seen my family only a handful of times and missed a few once-in-your-lifetime events of my grandchildren, and I haven’t turned off my cell or taken a day without work emails. COVID-19 has disrupted my life in ways both big and small. Fortunately, my family understands my sense of obligation and is supportive of my personal mission to push forward studies of potentially life-saving therapeutic and preventive interventions via the COVID Clinical Trials Unit.
What are the biggest challenges ahead in the search for a COVID-19 vaccine?
The first challenge was deciding which of the many vaccine studies we would offer. In consultation with the basic scientists, I learned as much as possible about the various novel vaccine platforms being developed and then made an executive decision to offer the trials of three vaccines, in addition to any that may be developed at Mount Sinai. One of the three vaccine uses messenger RNA (mRNA) to carry genetic instructions that prompt human cells to produce antibodies to COVID-19; another uses DNA to carry this kind of instruction; and the third, more traditional, vaccine uses a common adenovirus as a vector, or delivery system. Then we had to decide which sponsors to contract with. We have completed enrollment of 280 diverse participants in the Pfizer mRNA vaccine trial, which is expected to be the first vaccine to get an emergency use authorization at the end of this year or early next year. And this week, we opened the Janssen/Johnson & Johnson adenovirus vector vaccine at Mount Sinai Brooklyn and Mount Sinai Queens.
The biggest challenge will be assuring that every vaccine given emergency use authorization (EUA) has adequate safety, tolerability, immunogenicity, and efficacy despite the record pace at which they are being developed and tested. An EUA designation means that the vaccine may be beneficial; it does not mean that it is beneficial, which is a subtle distinction for the general public. If a vaccine is rushed into EUA and is later found to be unsafe or ineffective, there could be grave consequences for future vaccine acceptance and public trust. Appropriate expectations for the vaccine also have to be clearly conveyed. It will likely not bring an immediate end to COVID-19 by itself, but rather will become one of many measures in the prevention toolbox. We still will need to wear masks, use hand hygiene, social distance, and stay home when sick.
The other major issue is how the vaccines will be distributed globally. Who receives the vaccine first? Who will distribute it, and how? Some of the vaccines currently in clinical trials require storage in a deep freeze and are only stable for a short time, but most pharmacies and doctors’ offices do not have ultralow freezers. Some vaccines require two doses, which doubles the effort required to deliver it. Even if an EUA is issued, vaccine trials will still need to continue, possibly for years, to determine which vaccine is the safest, most well tolerated, and most effective at preventing infection or disease. To do so, vaccine trial participants will need to be willing to continue in the trial, not knowing if they have received vaccine or placebo, even when they become eligible to receive vaccine through the EUA process. The trial sponsors will need to assure that those who received the placebo will eventually be offered an active vaccine when available.
There are many challenges, but there is also much optimism that globally we can end this pandemic together. Never before have we had so many tools and resources at hand to rapidly employ and implement yet still had so much uncertainty of what the future will bring.