Impact of SARS-CoV-2 in Hematopoietic Stem Cell Transplantation and Chimeric Antigen Receptor T Cell Therapy Recipients

Abstract

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 more than 600,000 deaths in the United States at the time of this report. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have a higher risk of mortality with COVID-19 owing to profound immune dysregulation. In this study, we investigated the impact of SARS-CoV-2 in HCT/CAR-T therapy recipients. This single-center prospective study included all (n = 58) adult HCT/CAR-T recipients who were diagnosed with COVID-19 at the University of Kansas Medical Center between March 2020 and May 2021. Baseline and disease-related characteristics were ascertained from medical records. Data were analyzed using SPSS version 21 (IBM, Armonk, NY). 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 recipients of allogeneic HCT (n = 32), autologous HCT (n = 23), and CAR-T therapy (n = 3). The median patient age was 58 years (range, 24 to 77 years), and 64% were males. The median time from HCT/CAR-T therapy to SARS-CoV-2 infection was 17.7 months (range, 0.2 to 201.9 months), and 22% of the patients acquired SARS-CoV-2 within the first 100 days post-HCT/CAR-T therapy. The primary hematologic disorders were plasma cell (36%), myeloid (38%), and 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%. Lymphopenia ( P = .049) and high serum ferritin concentration ( P = .020) were associated with mortality. COVID-19 severity was mild in 50% of the patients, moderate in 22%, and severe in 28%. Clinical findings included pneumonia or abnormal chest imaging (in 50%), hypoxia (28%), intensive care unit admission (19%), and mechanical ventilation (10%). Therapies included remdesivir (in 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 (range, 2 to 18.7 weeks), and 2 patients had a persistent infection for >5 months post-CAR-T therapy. After a median follow-up of 6.1 months (range, 0.5-13.6 months), the mortality rate was 16% in all patients and 28% in allogeneic HCT recipients. Among 9 patients who died, the median survival after SARS-CoV-2 infection was 23 days (range, 14 to 140 days). In survivors with moderate-severe COVID-19, the median time to recovery was 4.2 weeks (range, 1.1 to 24.7 weeks). Among allogeneic HCT...

Coronavirus disease 2019 in immunocompromised patients: a comprehensive review of coronavirus disease 2019 in hematopoietic stem cell recipients

“…As reported for other immunocompromised patients (solid organ transplantation (SOT), solid tumors) [ 2 ▪▪ ], most HSCT recipients displayed lymphopenia at the time of infection, while median leukocyte and neutrophil counts were within the normal range [ 2 ▪▪ , 6 ▪▪ , 7 , 9 ▪ , 10 – 12 , 15 ]. In the series from Shah et al [ 9 ▪ ], COVID-19 was associated with a reduction in all lymphocytes subsets, not only including CD4 and CD8 T cells but also B lymphocytes and natural killers.…”

“…In the largest published studies focusing on adult HSCT recipients with COVID-19 (Table 1 ), median age ranged from 35 to 67 years and most of patients were men [ 2 ▪▪ , 4 , 6 ▪▪ , 7 , 8 ▪▪ , 9 ▪ , 10 – 12 ].…”

Severe acute respiratory syndrome coronavirus 2 infection in the stem cell transplant recipient − clinical spectrum and outcome

“…The combined effect of ongoing immunosuppression, SARS-CoV-2-induced immune dysregulation, prolonged hospital and intensive care unit (ICU) stay and immunomodulatory therapies – such as dexamethasone or anti-IL-6 agents – may contribute to the development of infectious complications, either as co-infection at presentation or most commonly during the disease course. The incidence rates of microbiologically confirmed superimposed infections range from 13% to 25% [ 15 , 17 ▪ , 19 ]. Most reported episodes were bacterial, with predominance of hospital-acquired pathogens such as methicillin-resistant Staphylococcus aureus or nonfermenting Gram-negative bacilli.…”

“…Some studies have observed higher serum procalcitonin levels in recipients with co-infection as compared to those free from this complication [ 17 ▪ ]. The diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA) has been only occasionally reported [ 15 , 17 ▪ , 25 , 26 ], and HSCT recipients are marginally represented in case series of CAPA [ 27 , 28 ]. There have been also an anecdotal report of an aseptic meningitis with negative reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 in the cerebrospinal fluid after initial clinical recovery from COVID-19, suggesting a potential pathogenic role for molecular mimicry [ 29 ].…”

“…After a median follow-up of 6.1 months, all-cause mortality in the overall cohort was 16.3%, reaching 28.1% among allo-HSCT recipients. Prior grade II–IV acute GvHD, immunosuppression and allo-HSCT (compared to auto-HSCT or CAR-T therapy) were associated with the combined outcome of illness severity [ 15 ].…”