The impact of COVID-19 on pediatric hematopoietic stem cell transplant recipients

From Dr. Neel Bhatt, Clinical Research Division, and the Center for International Blood and Marrow Transplant Research

After over two years living in the COVID-19 pandemic, most people are aware of the symptoms of infection – cough, sore throat, fever – and fortunately, thanks to large-scale vaccination efforts for a majority of people, whilst unpleasant, a diagnosis of COVID-19 leads to mild/moderate illness. However, a subset of the population remains at higher risk for severe illness from COVID-19, particularly those who are immunocompromised. Patients who have undergone hematopoietic stem cell transplant (HSCT) fall into this category and are at increased risk for disease complications, such as requiring mechanical ventilation during treatment for COVID-19, in addition to worse overall outcomes. The impact on the pediatric population is less well understood. Severe COVID-19 and deaths after diagnosis among children and adolescents have been consistently lower when compared to the adult population, but does this remain true for pediatric HSCT recipients? Dr. Neel Bhatt, an Assistant Professor and Pediatric Hematologist-Oncologist in Fred Hutch’s Clinical Research Division, led a recent study that aimed to better understand the impact of a COVID-19 diagnosis on pediatric HSCT recipients. The study, recently published in Transplantation and Cellular Therapy, focused on determining overall survival after COVID-19, and secondary risk factors attributed to poorer outcomes. Discussing the premise of the study, Dr. Bhatt said “to our knowledge, this is the largest international series to date summarizing the cumulative incidence, risk factors, treatment patterns, and outcomes of pediatric HSCT recipients with COVID-19. Before our analysis, there was very limited literature describing outcomes of pediatric HSCT recipients after COVID-19. From prior studies, we know that patients with compromised immune systems due to malignancies, active cancer treatment, ongoing immune suppression, or those undergoing hematopoietic cell transplant are at a higher risk of adverse outcomes after COVID-19; but these studies primarily focused on adults. A previous analysis from our group including 318 HSCT recipients showed that survival at 30 days after COVID-19 for allogeneic HSCT recipients was 68% and 67% for autologous HSCT recipients. However, pediatric HSCT recipients comprised <10% of this cohort. While prior studies have shown that children in general have a lower risk of moderate to severe COVID-19 compared to adults, we did not really know the outcomes of pediatric HSCT recipients after COVID-19.”

Overall mortality among pediatric hematopoietic stem cell transplant recipients was low after diagnosis with COVID-19.
Overall mortality among pediatric hematopoietic stem cell transplant recipients was low after diagnosis with COVID-19. Figure provided by Dr. Bhatt.

The Center for International Blood and Marrow Transplant Research (CIBMTR) is an international database, formed through collaboration between the National Marrow Donor Program/Be the Match® and the Medical College of Wisconsin, that collects data about HSCT procedures performed at hundreds of global transplant centers. Using this resource, the authors were able to gather clinical data and COVID-19 status for 167 pediatric HSCT recipients. Most study participants were diagnosed with mild/moderate COVID-19, and, notably, when determining overall mortality risk from COVID-19 for this population, 45-day survival rates for transplants performed in the US were high, at 98%. This survival statistic dipped for transplants performed outside of the US (87%), with the authors postulating that this may be partly due to global disparities in COVID-19 care. The authors next utilized the hematopoietic cell transplantation comorbidity index to determine potential risk of a COVID-19 diagnosis. Pediatric HSCT patients who had a higher comorbidity score (examples of comorbidities include obesity, diabetes, infection) were more likely to be diagnosed with COVID-19, than those patients with a lower score. Summarizing their findings, Dr. Bhatt stated “Our analysis showed that the overall disease severity and mortality was lower when compared with previously published data on adult HSCT recipients. That could be in part due to the median duration between HSCT and COVID-19 diagnosis being more than one year, which has been identified as a risk-factor in our previous analysis. Additionally, only a very small number of patients were on any immune suppression before COVID-19 or required any oxygen/ventilatory support. It is important to note that the mortality was still higher than previously reported general pediatric mortality rates after COVID-19. The difference in mortality rates between pediatric HSCT recipients and the general pediatric population could be explained by nascent immune systems and overall organ impairment due to treatment-related toxicities among HSCT recipients.”

The ever-evolving landscape of the COVID-19 pandemic and continuous emergence of new viral strains means that additional research to provide insight into the impact of COVID-19 on pediatric HSCT recipients is essential. “Our study analyzed data on pediatric HSCT recipients diagnosed with COVID-19 between March 2020 and May 2021, submitted to the CIBMTR. Given the timing of our analysis, it pre-dates the emergence of variants of concern such as delta (B.1.617.2) and omicron (B.1.1.529) and the Food and Drug Administration announcement authorizing emergency use of the Pfizer-BioNTech COVID-19 vaccine for children and adolescents (5-15 years of age). Given the dynamic nature of the COVID-19 pandemic and the constantly evolving treatment paradigm, it would be pivotal to assess the outcomes of HSCT recipients at frequent intervals to understand the implications of emerging SARS-CoV-2 variants of concern and protection conferred by COVID-19 vaccination and treatment regimens. We believe that the findings from our study will provide a benchmark for such future studies focusing on this population. CIBMTR continues to voluntarily collect data from centers and we plan to conduct subsequent analyses focusing on these questions,” concluded Dr. Bhatt. 

This work was supported through funding sources that assist the CIBMTR.

Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Neel Bhatt contributed to this research.

Bhatt NS, Sharma A, St Martin A, Abid MB, Brown VI, Diaz Perez MA, Frangoul H, Gadalla SM, Herr MM, Krem MM, Lazarus HM, Martens MJ, Mehta PA, Nishihori T, Prestidge T, Pulsipher MA, Rangarajan HG, Williams KM, Winestone LE, Yin DE, Riches ML, Dandoy CE, Auletta JJ. Clinical Characteristics and Outcomes of COVID-19 in Pediatric and Early Adolescent and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Cohort Study. Transplant Cell Ther. 2022 Jul 4:S2666-6367(22)01436-1. doi: 10.1016/j.jtct.2022.06.026. Epub ahead of print. PMID: 35798233; PMCID: PMC9251957.