Coronavirus disease 2019 (COVID-19), a respiratory illness caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in March 2020, and has caused over a half-million deaths in the US. Hematopoietic stem cell transplant (HCT) or chimeric antigen receptor-T cell therapy (CAR-T) recipients have a higher risk of mortality with COVID-19 due to profound immune dysregulation.
In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T recipients.
We conducted a single-center prospective study, including all (n=58) adult HCT/CAR-T patients who were diagnosed with COVID-19 at the University of Kansas Medical Center from March 2020 to May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (SPSS Inc, Chicago, IL). Bivariate analyses, using the chi-square and t-test, and logistic regression analyses were conducted.
The study included 58 HCT/CAR-T patients who acquired SARS-CoV-2 infection, including allogeneic HCT (n=32), autologous HCT (n=23), and CAR-T (n=3) recipients. The median age was 58 (24-77) years and 64% were males. Median time since HCT/CAR-T to SARS-CoV-2 infection was 17.7 (0.2-201.9) months, and 22% of patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T. Primary hematologic disorders were plasma cell (36%), myeloid (38%), or lymphoid (26%) malignancies. Myeloablative conditioning was performed in 62% of patients. Donors were autologous (45%), matched sibling (15%), matched unrelated (21%), and haploidentical (19%). Prior history of grade II-IV acute graft-versus-host disease (GVHD), active GVHD, and current immunosuppressive therapy (IST) was noted in 22%, 31%, and 36% of patients respectively. Concurrent infections were observed in 19% of patients. Lymphopenia (p=0.049) and high ferritin (p=0.020) were associated with mortality. COVID-19 severity was mild (50%), moderate (22%), or severe (28%). Clinical findings included pneumonia or abnormal chest imaging (50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (41%), convalescent plasma (35%), dexamethasone (22%), monoclonal antibodies (19%), and tocilizumab (3%). The median duration of viral shedding (positive SARS-CoV-2 PCR) was 7.7 weeks (2-18.7) and 2 patients (post-CAR-T) had a persistent infection for over 5 months. After a median follow-up of 6.1 (0.5-13.6) months, the mortality rate was 16% in all patients and 28% in allo-HCT patients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 (14-140) days. In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (1.1-24.7). Among allo-HCT recipients, 5 patients (16%) developed subsequent pulmonary chronic GVHD requiring systemic steroids and additional immunosuppression. Significant predictors of COVID-19 severity included allo-HCT (OR 3.6, 95% CI 1.2-10.8, p=0.020), history of grade II-IV acute GVHD (OR 4.6, 95% CI 1.10-18.86, p=0.036) and concurrent IST (OR 5.9, 95% CI 1.8-19.8, p=0.004).
Hematopoietic stem cell transplant and CAR-T cell therapy recipients are at an increased risk of moderate-severe COVID-19 pneumonia and higher mortality with SARS-CoV-2 infection. Our findings confirm the need for continuing vigilance with social distancing and masks, vaccination prioritization, close monitoring, and aggressive treatment in HCT/CAR-T patients.
Copyright © 2021. Published by Elsevier Inc.
About The Expert
Muhammad Umair Mushtaq
Moazzam Shahzad
Sibgha Gull Chaudhary
Mary Luder
Nausheen Ahmed
Haitham Abdelhakim
Rajat Bansal
Ramesh Balusu
Shaun DeJarnette
Clint Divine
Robert Kribs
Leyla Shune
Anurag K Singh
Siddhartha Ganguly
Sunil H Abhyankar
Joseph P McGuirk
References
PubMed