Transfer of COVID-19 Immunity Between Allogeneic Transplant Donors and Recipients

The novel coronavirus, SARS-CoV-2, the agent causing COVID 19 respiratory syndrome has caused a global pandemic, with a toll of significant morbidity and mortality. SARS-CoV-2 infection is expected to be very serious in the vulnerable population of non-Hodgkin lymphoma (NHL) patients, who received an allogeneic hematopoietic stem cell transplant (HCT), as a curative procedure for relapsed NHL (Project 1). Due to their immunocompromised status, HCT recipients are at increased risk for severe COVID 19 disease, including respiratory complications and exacerbated lethality of the infection. There are still critical gaps in our knowledge of the immune response and its role in clinical manifestations of COVID 19, in HCT recipients. In transplant practice, we know that donor immunity can often be transferred to the recipient as part of the graft. Hence, our goal is to investigate if viral immunity is transferred from the HCT donor, who was exposed to COVID 19, to the HCT recipient. SARS-CoV-2 donor derived immunity could benefit the recipient, contributing to reduced COVID 19 morbidity and mortality, and improving HCT outcomes in high risk NHL recipients. Our previous and ongoing studies with cytomegalovirus (CMV), a respiratory virus causing major post-HCT complications, laid the groundwork for the design of the current proposal. Data from our group demonstrated that donor-derived CMV specific immunity can benefit post-transplant outcomes, by reducing the duration and recurrent need of antiviral treatment in the HCT recipient. Additionally, vaccinating donor and/or recipient posttransplant with Triplex, a CMV vaccine developed by our team at City of Hope (COH), augments protective antiCMV immunity. These clinical data lead to our hypothesis that a HCT donor, recovering from COVID 19, will transfer protective antiviral immunity to the HCT recipient. Guided by our established experience in transplant immunology, we propose a one-year observational study to pursue the objective of characterizing levels, quality, and duration of SARS-CoV-2 immunity, which could protect against viral infection when transferred from matched (sibling or unrelated) and half-matched (haploidentical) family donors to HCT recipients. Specimens from SARSCoV-2 seropositive donor/recipient pairs will be extensively assessed for the presence of functional antiviral immune responses. The immune monitoring study will focus on the six months interval post-HCT, when immunity in HCT recipients is mostly donor derived, to assess whether SARS-CoV-2 immunity transfer occurs, and contributes to protection against serious COVID 19. Our proposed research will broadly impact the transplant field, by providing critical information on the role of protective donor-derived SARS-CoV-2 immunity in HCT recipients, during immune reconstitution. This study will also lay the ground work for the use of a novel COH COVID 19 vaccine in the transplant setting, with the goal of amplifying the HCT donor immune response to SARS-CoV-2, and/or eliciting protective immunity by immunizing the recipient.