Successful outcome of pre-engraftment COVID-19 in an HCT patient: impact of targeted therapies and cellular immunity

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell transplantation (HCT). Here we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by RT-PCR on day -1 of matched unrelated donor (SARS-CoV-2 IgG negative) T-cell-replete HCT. This experience allowed for implementing a virologic and immunomonitoring panel to characterize the impact of SARS-CoV-2 on the recipient's nascent humoral and cellular immune response. The finding of robust, functional, and persistent levels of SARS-CoV-2 specific T-cells, starting early after transplant was unexpected, and in combination with the clinical strategy may have contributed to the favorable outcome. Additionally, it is plausible that pre-existing cross-reactive endemic coronavirus immunity in the allogeneic graft reduced recipient susceptibility to COVID-19 disease. This case supports the critical role that T-cell responses may play in mitigating SARS-CoV-2 infection, even in the context of transplant immunosuppression, in which reconstitution of humoral response is commonly delayed. Interventional approaches to transfer SARS-CoV-2-specific cellular immunity such as HCT donor vaccination and adaptive cellular therapy could be of benefit.

Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study

“…To our knowledge, this is the first reported evidence of the possible protective role of donor-derived SARS-CoV-2 T cells in recipients who survived post-HCT COVID-19. This study outcome confirms that donor-derived SARS-CoV-2 T-cell-mediated responses can be preserved in immunosuppressed patients during immune-specific reconstitution and can increase COVID-19 vaccination effectiveness (12,16,24,43), even in the presence of ongoing immunosuppressive treatment (5,44).…”

“…The gradual but continuous decline of the SARS-CoV-2 adaptive humoral response observed in the first 6 months post-HCT (Figure 3) is in sharp contrast with the concomitant growing trajectory of donor-derived SARS-CoV-2-specific cellular responses, measured in the recipients during the same post-HCT timeframe. This result supports the notion of delayed B-cell functional reconstitution and adaptive humoral immune recovery post-HCT (43,49). SARS-CoV-2-specific humoral response profiles in patients who received a licensed COVID-19 vaccine or had SARS-CoV-2 infection pre-transplant were both of donor and recipient origin and therefore difficult to interpret.…”

“…As the early post-HCT immune deficit gradually improved, levels of donor-derived SARS-CoV-2-mediated cell immunity increased and closely mirrored those measured in HCT donors by 6 months post-HCT (Figure 1). This interesting finding strongly suggests that donor SARS-CoV-2-specific T cells are preserved and can actively proliferate post-HCT during immune reconstitution (12,24,43). Donor-derived SARS-CoV-2-specific CD4 + T-cell responses in the recipients were predominant compared to CD8 + T-cell responses, as typically observed in healthy individuals infected with COVID-19 (39).…”

“…TCM is also known for its ability to persist in circulation, proliferate, and give rise to effector T cells (48). Collectively, our data suggest that functionality of T-cell subset dominance and memory phenotypes of donor-derived SARS-CoV-2-specific T cells were preserved early post-HCT, and donor T-cell frequency was restored by 6 months post-HCT (12,24,43).…”

Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia

“…Two reports are available on performing allo-HSCT during active SARS-CoV-2 infection, both diagnosed during conditioning chemotherapy. The first patient received remdesivir and convalescent plasma, experiencing at neutrophil engraftment a cytokines release syndrome associated with mild pneumonia, successfully cured with remdesivir again, casirivimab/imdevimab, tocilizumab and methylprednisolone ( 17 ). The second patient received a transplant from a donor with asymptomatic SARS-CoV-2 infection, developing a transient respiratory failure shortly after PBSC infusion ( 18 ).…”