COVID-19 Partnerships: Katharine Bar, University of Pennsylvania

During the COVID-19 pandemic, ArgoPond provided services to several research teams by leading clinical trial Data and Safety Monitoring Boards (DSMBs) and assisting with other clinical research strategic oversight. We are excited to present a series of interviews with some of these researchers, who effectively conducted clinical trials during a remarkable moment in history. In this blog, we speak with Dr. Katharine Bar of the University of Pennsylvania Perelman School of Medicine.

Dr Katharine Bar, Virologist and Director, Virus and Reservoirs Core, Penn CFAR

Dr. Katharine Bar, MD

Assistant Professor of Medicine

Division of Infectious Diseases

Director, Virus and Reservoirs Core, Penn Center for AIDS Research

University of Pennsylvania

The Leader and Her Research Focus Prior to the Pandemic

Dr. Katharine Bar is an infectious disease physician with clinical and basic science expertise in HIV at the University of Pennsylvania. A graduate of the University of Iowa College of Medicine, she completed her internal medicine residency at Virginia Commonwealth Univers`ity, where she also served as chief resident. Katharine completed her infectious disease training at the University of Alabama-Birmingham and joined the faculty at Penn in 2012 as an up-and-coming expert in translational HIV research.

In addition to her clinical practice in Infectious Disease, she leads a laboratory working on molecular and translational virology within the University of Pennsylvania Center for AIDS Research. At the CFAR, she directs the Virus and Reservoirs Core. Of particular interest to Katharine and her team are neutralizing antibodies in HIV – antibodies that are capable of either rendering the virus noninfectious or targeting it for destruction.

Why She Pivoted to a COVID-19 Trial

In many ways, the COVID-19 pandemic was something Dr. Bar had been training for her entire professional career. As a member, and often a leader, of large multicenter HIV trials, she had deep familiarity with the details of clinical studies of life-threatening viral infections. Furthermore, her expertise with neutralizing antibodies made her an obvious choice for a trial using convalescent plasma.

Although convalescent plasma is most widely considered a source of neutralizing antibodies, the material contains many other immune mediators that might impact the clinical course of COVID-19. (Autoimmunity Reviews Volume 19, Issue 7, July 2020, 102554)

As shown in the figure above, convalescent plasma is a non-cellular fraction of blood that is donated by a patient who has recovered (that is, convalesced) from COVID-19. It is harvested much like blood is donated. The component of plasma that is felt to be most important are antibodies against the SARS-CoV-2 virus, and in particular against the spike protein, which is what the virus uses to infect cells.  All plasma is tested prior to use for safety and its content of these antibodies. As the figure shows, there are many other components within that unit of liquid that, while incompletely understood, may be beneficial to struggling patients.

Historically, convalescent plasma has been used to treat other infectious diseases. Shortly after the onset of the COVIC-19 pandemic, some physicians recognized that there might be a role for convalescent plasma in the treatment of the sickest patients. At the University of Pennsylvania Perelman School of Medicine, the research and clinical leadership understood immediately that Katharine, with her basic science and clinical trials expertise, was an ideal physician-scientist to lead the convalescent plasma effort.

She was quickly convinced. ‘When the whole world seems to be falling apart, it is rewarding to try to do something to help.’

The Trials: A Study of Convalescent Plasma in Mechanically Ventilated COVID-19 Patients; a Randomized Trial in Severely Ill Patients

The studies Katharine and her team designed acknowledged two important facts. First, much was still unknown about the benefit of convalescent plasma, and it wasn’t guaranteed that the material would be safe or helpful when used in this setting. Second, the most severely affected patients were truly life-threatened, and without another proven therapy available, plasma might represent a last best hope for recovery.

Their approach was to design two trials. The first focused on the most severely ill patients, those requiring mechanical ventilation to survive. Rather than randomized some patients to not receiving the therapy, they made it available to many critically ill patients and took advantage of an ongoing NIH-sponsored trial to provide a type of ‘control’ group of similar patients enrolled elsewhere who did not receive plasma.

In the second trial, a more familiar trial strategy was employed – with patients randomized to receive either convalescent plasma or the current best standard of care.

At the time of this writing, both trials have closed enrollment – with 112 patients cared for between the two studies – and their results are being analyzed. The final conclusions of each trial are expected later this spring.

The Biggest Surprises

Like other researchers we’ve worked with, Dr. Bar says the biggest surprise was how challenging it was to carry out the trials when the ground was shifting so quickly. New information was arriving daily about the disease and how it might be best treated, so the ‘standard of care’ against which her therapies were being compared was constantly improving. The health system was updating recommendations and policies very frequently throughout the spring and summer, meaning the daily routines of the trials had to be updated just as frequently. Lastly, as additional new studies were being announced almost weekly, the research teams at Penn established standing daily meetings to determine which clinical trial best suited individual patients that wished to participate in the important work of finding new treatments.

Although the circumstances required that Katharine quickly establish two small, single center studies, she appreciates the power of the large multicenter trials with which she has the most experience leading. ‘It’s important at many levels: as an investigator, an institution, and a country, that we be prepared to quickly contribute to really high-quality evidence building.’ Small trials can rapidly establish plausibility of a new treatment, but large cooperative efforts are needed to definitively accept or reject new ideas. ‘The beginning of the pandemic may have been too entrepreneurial,’ she notes, ‘with so many scientists advancing so many different ideas. In the future, a strategy for efficiently graduating promising ideas into multicenter trials would help reduce a lot of the therapeutic uncertainty we faced in 2020, and continue to face today.’

Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption

HIV-1 latent reservoir size and diversity are stable following brief treatment interruption.

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.