COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA) (preprint)

Patients with acute myeloid leukemia (AML) are at high risk of mortality from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients with COVID-19 diagnosis between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the prior 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died. Death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%). Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with an improved survival when AML treatment could be delayed. Patients with COVID-19 diagnosis between January and August 2020 had a significantly lower survival. COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment.

Human Erythroid Progenitors are Directly Infected by SARS-CoV-2: Implications for Hypoxia and Emerging Hematopoiesis/Erythropoiesis in COVID19 (preprint)

We document here that intensive care COVID19 patients suffer a profound decline in hemoglobin levels but show an increase of circulating nucleated red cells, suggesting that SARS-CoV-2 infection either directly or indirectly induces stress erythropoiesis. However, the impact of SARS-CoV-2 on erythropoiesis has not been well investigated. We show that ACE2 expression peaks during erythropoiesis and renders erythroid progenitors vulnerable to infection by SARS-CoV-2. In particular, we characterize two erythroid progenitor populations as primary targets for the virus. Early erythroid progenitors, defined as CD34-CD117+CD71+CD235a-, show the highest levels of ACE2 and constitute the primary target cell to be infected during erythropoiesis. In addition, SARS-CoV-2 can also bind and infect mid-late erythroid precursors, defined as CD34-CD117-CD71+CD235a+. Our findings constitute the first report of SARS-CoV-2 infectivity in erythroid progenitor cells and can contribute to understanding both the clinical symptoms of severe COVID19 patients and how the virus can spread through the circulation to produce local inflammation in tissues, including the bone marrow.Funding: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001045), the UK Medical Research Council (FC001045) and the Wellcome Trust (FC001045) to DB.Conflict of Interest: The authors declare no competing interests.Ethical Approval: Peripheral blood was isolated from consenting unscreened healthy adult volunteers following approved protocols by the ethics board of the Francis Crick Institute and the regulations of the Human Tissue act 2004. Peripheral blood mononuclear cells (PBMCs) were isolated by centrifugation over a Histopaque-1119 gradient (Sigma-Aldrich 11191).