Phenotypical changes of hematopoietic stem and progenitor cells in COVID-19 patients: Correlation with disease status

Abstract

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.

Keywords: COVID-19; SARS-CoV-2; hematopoietic progenitor cells (HPCs); hematopoietic stem cells (HSCs).

Fig. 1

Gating strategy of HSCs and their subpopulations. A) Gating on CD34+/lin(CD3/19/33/14)– population. B) CD34+/lin(CD3/19/33/14)– populations were further gated on CD38 and CD45RA expression. C) Within CD34+/lin(CD3/19/33/14)– CD38–CD45RA– population, CD90+CD49f+ expression defined HSCs and CD90–CD49f– expression defined MPPs. D) CD34+/ lin(CD3/19/33/14)– CD38+CD45RA– population were further subdivided into CD45RA– CD123+ (CMPs), and CD45RA– CD123– (MEPs) compartments. E) Within the CD34+/lin(CD3/19/33/14)–CD38+CD45RA+ population, CD123+ expression defined the GMP compartment

Fig. 2

Heat map showing baseline characteristics and laboratory features of the 48 COVID-19 patients

Fig. 3

Comparison of the percentages of HSCs and MPPs in COVID-19 patients versus recovered and healthy controls. A) HSCs, B) MPPs, C) CMPs, D) GMPs, and E) MEPs. The p value: *p < 0.05, ***p < 0.001, ****p < 0.0001 indicated the significant correlation among different groups

Fig. 4

Comparison of the percentages of HSCs and HPPs between severe and non-severe COVID-19 patients. A) HSCs, B) MPPs, C) CMPs, D) GMPs, and E) MEPs. Asterisks indicate significant correlations among different groups with the following p values: **p < 0.01, ****p < 0.0001

Fig. 5

Levels of CRP, D-dimer, and ferritin and their correlation with HSCs and their subpopulations in severe and non-severe COVID-19 patients. Levels of CRP (A), D-dimer (B), and ferritin (C). Relationships between levels of CRP, D-dimer, and ferritin and percentages of HSCs (D, E), MPPs (G-H). Asterisks indicate significant correlations among different groups with the following p values: **p < 0.01, ***p < 0.001, ****p < 0.0001

Fig. 5

Levels of CRP, D-dimer, and ferritin and their correlation with HSCs and their subpopulations in severe and non-severe COVID1-19 patients. MPPs (I), CMPs (J-L), GMPs (M-O), and MEPs (P)

Fig. 5

Levels of CRP, D-dimer, and ferritin and their correlation with HSCs and their subpopulations in severe and non-severe COVID1-19 patients. MEPs (Q, R)

Fig. 6

ROC curve analysis for evaluation of the diagnostic performance of HSCs, HPCs CRP, D-dimer, and ferritin in differentiating between healthy controls and COVID-19 patients (A) and severe and non-severe cases of COVID-19 (B, C)