A rationale to prioritise vaccination of HSCT patients against COVID-19.

Patients who are frail or have significant comorbidities are especially susceptible to severe acute respiratory syndrome coronavirus 2 infection, and are more likely to develop severe disease, with a higher risk of death than in the general population. This increased risk is notably true for patients with cancer, including those with haematological malignancies.1, 2, 3 When such patients receive a haematopoietic stem-cell transplantation (HSCT), either allogeneic or autologous, it is possible that their vulnerability to COVID-19 would increase further because of the profound and long-lasting immunosuppression, as well as specific organ toxicities, induced by these procedures. Unfortunately, data on this issue are scarce, with existing data mostly coming from single-centre studies. Although these studies tend to show a high rate of mortality among HSCT recipients with COVID-19, their lack of robustness and statistical power precludes the drawing of firm conclusions and identifying specific risk factors associated with survival in this context.

In The Lancet Haematology, Akshay Sharma and colleagues report on 318 HSCT recipients (184 allogeneic HSCT and 134 autologous HSCT) across various transplantation centres mainly based in the USA, who were diagnosed with COVID-19 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. The insufficiency of robust data from large-scale cohorts in this high-risk population renders the present study of importance for physicians caring for HSCT recipients worldwide.

Two important messages can be drawn from the results reported by Sharma and colleagues. The first is the confirmation that the prognosis of COVID-19 is particularly poor in HSCT recipients, and that its prevention, in the absence of any specific curative treatment with sufficient efficacy, should be at the forefront of concerns. Despite the fact that most patients in the study were diagnosed more than 1 year post transplantation, and that only 34 (18%) of 184 allogeneic HSCT recipients had received immunosuppression within 6 months of COVID-19 diagnosis, at least 45 (14%) of 318 had severe disease requiring mechanical ventilation and 66 (21%) had died, with COVID-19 being the primary cause of death in the majority of cases. Consequently, the probability of overall survival at 30 days after the diagnosis of COVID-19 (ie, the main endpoint of this study) was poor, at 68% (95% CI 58–77) for allogeneic HSCT and 67% (55–78) for autologous HSCT recipients.

The second important finding is the identification of risk factors associated with death from COVID-19 in this setting. Besides risk factors that have already been identified in the general population (ie, male sex and age—although a cut-off of 50 years was retained in this study), some transplantation-specific factors also seem to affect prognosis, with time from allogeneic HSCT to COVID-19 associated with an almost three-times increased risk of death when less than or equal to 12 months. Regarding autologous HSCT, the underlying haematological disease had a significant effect on survival, with a higher risk of death observed in patients transplanted for lymphoma, as compared with plasma cell disorder and myeloma. Lymphopenia of less than 0·3 × 109 cells per L at time of COVID-19 diagnosis was also associated with worse overall survival.

Sharma and colleagues' study has several significant limitations, mostly related to its retrospective nature. Notably, the amount of missing data is substantial, follow-up is short, and the risk of a selection bias is quite high. Therefore, further large and well designed studies with longer follow-up are needed to confirm and refine the results from the CIBMTR experience and, possibly, address some of the questions that remain unanswered. Do long-term survivors of HSCT, who are at higher risk of developing diabetes, hypertension, and cardiovascular events, also have a worse survival as compared with the general population? How does COVID-19 affect the general health condition of the patients and other transplantation-related outcomes? Do the immunosuppressive drugs administered to allogeneic transplantation recipients, besides potentially increasing their vulnerability to COVID-19 infection, prevent or modify and eventually ameliorate the natural evolution of severe cases, as has been shown for dexamethasone in the general population? Can immunity from a COVID-19-seropositive donor be protective for the recipient after transplantation? Will vaccination protect HSCT patients as well as in the general population? A better understanding of the distinctive features of COVID-19 infection in HSCT recipients will be a necessary and essential step towards improvement of the remarkably poor prognosis observed in this setting.