COVID-19 in immunocompromised patients after hematopoietic stem cell transplantation: a pilot study

Abstract

Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients at early stage of immune reconstitution after hematopoietic stem cell transplantation (HSCT) are limited. In the present study, we retrospectively investigated the incidence and clinical features of SARS-CoV-2 infection in patients who underwent HSCT in 2022. Patients (allo-HSCT, n = 80; auto-HSCT, n = 37) were consecutively included in the study. The SARS-CoV-2 infection rate was 59.8%, and the median interval of HSCT to coronavirus disease 2019 (COVID-19) was 4.8 (range: 0.5-12) months. Most patients were categorized as mild (41.4%) or moderate (38.6%), and 20% as severe/critical. No deaths were attributable to COVID-19. Further analysis showed that lower circulating CD8⁺ T-cell counts and calcineurin inhibitor administration increased the risk of SARS-CoV-2 infection. Exposure to rituximab significantly increased the probability of severe or critical COVID-19 compared with that of mild/moderate illness (P < .001). In the multivariate analysis, rituximab use was associated with severe COVID-19. Additionally, COVID-19 had no significant effect on immune reconstitution. Furthermore, it was found that Epstein-Barr virus infection and rituximab administration possibly increase the risk of developing severe illness. Our study provides preliminary insights into the effect of SARS-CoV-2 on immune reconstitution and the outcomes of allo-HSCT recipients.

Keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Immunocompromised patients; Severe acute respiratory syndrome coronavirus 2.

Figure 1.

Flowchart of the study. allo-HSCT = allogeneic hematopoietic cell transplantation, auto-HSCT = autologous hematopoietic cell transplantation, NRM = non-relapse mortality, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2, SOS = sinusoidal obstruction syndrome.

Figure 2.

Swimmer plot of clinical characteristics among HSCT patients at diagnosis of COVID-19. CNI = calcineurin inhibitor, COVID-19 = coronavirus disease 2019, CR = complete remission, HCT-CI = hematopoietic cell transplantation-comorbidity index, HID = haploidentical donor, HSCT = hematopoietic cell transplantation, MAC = myeloablative conditioning, MMUD = mismatched unrelated donor, MRD = measurable residual disease, MSD = matched sibling donor, MUD = matched unrelated donor, NR = non remission, RIC = reduced intensity conditioning.

Figure 3.

Swimmer plot of clinical characteristics among mild/moderate and severe/critical SARS-CoV-2 infections. CNI = calcineurin inhibitor, COVID-19 = coronavirus disease 2019, CR = complete remission, HCT-CI = hematopoietic cell transplantation-comorbidity index, HID = haploidentical donor, HSCT = hematopoietic cell transplantation, MAC = myeloablative conditioning, MMUD = mismatched unrelated donor, MRD = measurable residual disease, MSD = matched sibling donor, MUD = matched unrelated donor, NR = non remission, RIC = reduced intensity conditioning, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Figure 4.

Factors affecting the severity of COVID-19 infection. Univariate (A) and multivariate (B) analysis of severe/critical illness predictors at diagnosis of COVID-19. (C) Comparison of severity between COVID-19 patients with or without rituximab administration. (D) Swimmer plot of the last infusion of rituximab and SARS-CoV-2 infection. ****P < .0001. ATG = anti-thymocyte globulin, CI = confidence interval, CNI = calcineurin inhibitor, COVID-19 = coronavirus disease 2019, EBV = Epstein–Barr virus, HSCT = hematopoietic cell transplantation, OR = odds ratio, SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

Figure 5.

Immune subsets within 6 mo after SARS-CoV-2 exposure. SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.