Consequences of coronavirus infections for primitive and mature hematopoietic cells: new insights and why it matters.

PURPOSE OF REVIEW: In recent history there have been three outbreaks of betacoronavirus infections in humans, with the most recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; causing Coronavirus disease 2019 [COVID-19]) outbreak leading to over two million deaths, with a rapidly rising death toll. Much remains unknown about host cells and tissues affected by coronavirus infections, including the hematopoietic system. Here, we discuss the recent findings examining effects that coronavirus infection or exposure has on hematopoietic cells and the clinical implications for these effects. RECENT FINDINGS: Recent studies have centered on SARS-CoV-2, demonstrating that hematopoietic stem and progenitor cells and mature immune cells may be susceptible to infection and are impacted functionally by exposure to SARS-CoV-2 Spike protein. These findings have important implications regarding hematologic complications arising from COVID-19 and other coronavirus-induced disease, which we discuss here. SUMMARY: Infection with coronaviruses sometimes leads to hematologic complications in patients, and these hematologic complications are associated with poorer prognosis. These hematologic complications may be caused by coronavirus direct infection or impact on primitive hematopoietic cells or mature immune cells, by indirect effects on these cells, or by a combination thereof. It is important to understand how hematologic complications arise in order to seek new treatments to improve patient outcomes.

Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein.

Despite evidence that SARS-CoV-2 infection is systemic in nature, there is little known about the effects that SARS-CoV-2 infection or exposure has on many host cell types, including primitive and mature hematopoietic cells. The hematopoietic system is responsible for giving rise to the very immune cells that defend against viral infection and is a source of hematopoietic stem cells (HSCs) and progenitor cells (HPCs) which are used for hematopoietic cell transplantation (HCT) to treat hematologic disorders, thus there is a strong need to understand how exposure to the virus may affect hematopoietic cell functions. We examined the expression of ACE2, to which SARS-CoV-2 Spike (S) protein binds to facilitate viral entry, in cord blood derived HSCs/HPCs and in peripheral blood derived immune cell subtypes. ACE2 is expressed in low numbers of immune cells, higher numbers of HPCs, and up to 65% of rigorously defined HSCs. We also examined effects of exposing HSCs/HPCs and immune cells to SARS-CoV-2 S protein ex vivo. HSCs and HPCs expand less effectively and have less functional colony forming capacity when grown with S protein, while peripheral blood monocytes upregulate CD14 expression and show distinct changes in size and granularity. That these effects are induced by recombinant S protein alone and not the infectious viral particle suggests that simple exposure to SARS-CoV-2 may impact HSCs/HPCs and immune cells via S protein interactions with the cells, regardless of whether they can be infected. These data have implications for immune response to SARS-CoV-2 and for HCT. Graphical Abstract • Human HSCs, HPCs, and immune cells express ACE2 on the cell surface, making them potentially susceptible to SARS-CoV-2 infection. • SARS-CoV-2 S protein, which binds to ACE2, induces defects in the colony forming capacity of human HPC and inhibits the expansion of HSC/HPC subpopulations ex vivo. These effects can be at least partially neutralized by treatment with SARS-CoV-2 targeting antibody, recombinant human ACE2, or Angiotensin1-7. • S protein also induces aberrant morphological changes in peripheral blood derived monocytes ex vivo. • Thus, there are many different manners in which SARS-CoV-2 virus may impact the functional hematopoietic system, which has important implications for hematological manifestations of COVID-19 (i.e. thrombocytopenia and lymphopenia), immune response, and hematopoietic stem cell transplant in the era of COVID-19.