During the COVID-19 pandemic, it quickly became clear that certain populations were particularly at risk for severe disease. Individuals undergoing hematopoietic cell transplants (HCT) or chimeric antigen receptor T-cell (CART) therapy for hematological malignancies were particularly at risk for severe disease, as these patients often undergo treatments which heavily reduce their immune cell reserves and leave them vulnerable to infections, including by SARS-CoV-2. Dr. Emily Rosen, now an infectious disease fellow in Dr. Catherine Liu’s Group in the Vaccine and Infectious Disease Division, described her experience working as a medical resident during the peak of the pandemic; “I saw first-hand the devastating impacts of COVID-19 on patients who are immunocompromised.”
Poor outcomes among immunocompromised populations were especially common during times of early circulating SARS-CoV-2 variants, Alpha and Delta, and prior to the widespread use of therapeutic interventions such as nirmatrelvir/ritonavir (Paxlovid), remdesivir and dexamethasone, among others. However, in late 2021, the Omicron variant arose as the dominant circulating strain, and we have since seen a reduction in virulence overall. In the wake of the changing landscape of COVID-19, Dr. Rosen and her colleagues were interested in understanding if these new, less pathogenic strains, as well as the increased use of effective COVID-19 therapeutics, might impact COVID-19 outcomes in HCT or CART recipients. The team recently published their findings in Transplantation and Cellular Therapy.
To study this, the research team conducted a retrospective cohort study of 65 Fred Hutch patients who had tested positive for SARS-CoV-2, after the emergence of Omicron, shortly before or after their cellular therapy. About half (54%) of their cohort had tested positive for SARS-CoV-2 prior to cellular therapy, and the post-cellular therapy patients were primarily HCT recipients. Prior to any patient’s COVID-19 diagnosis, most of the cohort (80%) had received at least 2 doses of a COVID-19 vaccine, and some had also received pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld). Most (80%) of the cohort had received at least one antiviral therapeutic following their COVID-19 diagnosis, including the commonly prescribed Paxlovid and remdesivir, as well as other therapies.
One observation the research team was glad to see, was that relatively few (12%) of their cohort had been hospitalized for COVID-19-related illnesses, split evenly between the pre- and post-cellular transplant recipients, and only one patient had severe infection. Dr. Rosen remarked that, “we were pleased to see that our study results support the conclusion that outcomes of COVID-19-related hospitalization and mortality appear to be improving in the HCT/CART population, compared to earlier in the pandemic.” They did, however, observe that there was a significant portion of patients (20%) who developed persistent COVID-19 - where they continued to test positive after 30 days, with or without symptoms. All of the patients with persistent COVID-19 had received some form of initial therapeutic, but only a few required additional treatment or hospitalization for the persistent infection. However, 3 of 8 pre-cellular therapy patients had a delay in their cellular therapy because of persistent COVID-19, highlighting the importance of understanding this clinical syndrome and how to prevent it.
Dr. Rosen and her colleagues believe that their study is an important piece in the, so far, small body of literature characterizing the risk of severe outcomes from COVID-19 in HCT and CART recipients, especially after the peak of the pandemic. Their cohort showed a decrease in severe outcomes from infection, consistent with similar studies, yet, as Dr. Rosen pointed out, “our study highlights that persistent COVID-19 is still a very relevant issue for this patient population.” The research team also noted that their cohort size was relatively small, and therefore more studies would be needed to “to compare outcomes in patients who received treatment for COVID-19 versus those who did not or compare efficacy among,” Dr. Rosen explained.
Building off this work, there are many future questions the team is excited to pursue, including determining optimal treatment strategies for COVID-19 in the HCT/CART population, preventing and treating persistent infection, and understanding if the different types of cellular therapy contribute to differences in risk of having poor COVID-19 outcomes. “It’s important to continue to study COVID-19 outcomes and treatment in the HCT/CART patient population to understand how we can continue to improve our clinical approach to COVID-19 treatment and use data to directly inform our daily clinical practice,” emphasized Dr. Rosen.
Rosen EA, Krantz EM, McCulloch DJ, Wilson MH, Tverdek F, Kassamali Escobar Z, Drucker D, Sanchez E, Ueda Oshima M, Mielcarek M, Gauthier J, Pergam SA, Hill JA, Liu C. COVID-19 Outcomes Among Hematopoietic Cell Transplant and Chimeric Antigen Receptor T-Cell Recipients in the Era of SARS-CoV-2 Omicron Variants and COVID-19 Therapeutics. Transplant Cell Ther. 2024 Aug 22:S2666-6367(24)00590-6. doi: 10.1016/j.jtct.2024.08.010. Epub ahead of print. PMID: 39179107.
This spotlighted work was funded by the NIAID and NCI.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Masumi Ueda Oshima, Marco Mielcarek, Jordan Gauthier, Denise McCulloch, Steven Pergam, Joshua Hill, Catherine Liu contributed to this work.