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URL: https://pubmed.ncbi.nlm.nih.gov/34087216/

⇱ Physical phenotype of blood cells is altered in COVID-19 - PubMed

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Abstract

Clinical syndrome coronavirus disease 2019 (COVID-19) induced by severe acute respiratory syndrome coronavirus 2 is characterized by rapid spreading and high mortality worldwide. Although the pathology is not yet fully understood, hyperinflammatory response and coagulation disorders leading to congestions of microvessels are considered to be key drivers of the still-increasing death toll. Until now, physical changes of blood cells have not been considered to play a role in COVID-19 related vascular occlusion and organ damage. Here, we report an evaluation of multiple physical parameters including the mechanical features of five frequent blood cell types, namely erythrocytes, lymphocytes, monocytes, neutrophils, and eosinophils. More than four million blood cells of 17 COVID-19 patients at different levels of severity, 24 volunteers free from infectious or inflammatory diseases, and 14 recovered COVID-19 patients were analyzed. We found significant changes in lymphocyte stiffness, monocyte size, neutrophil size and deformability, and heterogeneity of erythrocyte deformation and size. Although some of these changes recovered to normal values after hospitalization, others persisted for months after hospital discharge, evidencing the long-term imprint of COVID-19 on the body.

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Figures

👁 Figure 1
Figure 1
Scheme of an RT-DC measurement of a peripheral blood sample. 50 μL of venous citrate-anticoagulated blood is diluted and mixed gently in 950 μL of measurement buffer consisting of phosphate-buffered saline and methyl cellulose. The blood cell suspension is pumped through a microfluidic chip mounted on an inverted microscope, and single-cell images are processed in real time to obtain the physical parameters of each cell. During postprocessing, cell populations of interest are manually gated according to brightness, and the physical properties of each population are analyzed.
👁 Figure 2
Figure 2
Decreased size and deformability of erythrocytes of hospitalized COVID-19 patients. Typical scatter plot of erythrocyte deformation versus cell size (cross-sectional area) of a healthy blood donor with no known viral infection (A) compared with a patient 4 months after undergoing COVID-19 (B) and a patient with COVID-19 in an intensive care unit (C) is given. The erythrocytes shown in (D) are representative images of cells in the clusters marked by corresponding numbers in the scatter plot. (E) Kernel density estimate plots demonstrating the differences in cell size and deformation between the three donors (A–C). The comparison of median values of deformation (F) and SD of deformation (G) between the control group of blood donors (n = 24), recovered patients (n = 14), and patients hospitalized with COVID-19 (n = 17) is shown. Statistical comparisons were done using Kruskal-Wallis test with Dunn’s post hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
👁 Figure 3
Figure 3
Lymphocytes are less stiff in peripheral blood of hospitalized COVID-19 patients. Typical scatter plot of lymphocyte deformation versus cell size (cross-sectional area) of a healthy blood donor with no known viral infection (A) compared with a patient 4 months after undergoing COVID-19 (B) and a patient with COVID-19 in an intensive care unit (C) is given. (D) Kernel density estimate plots demonstrating the differences in cell size and deformation among the three donors (A–C). (E) Representative images of cells in the clusters marked by corresponding numbers in the scatter plots. (F) No significant differences in lymphocyte cell size were found between healthy blood donors (gray, n = 24), recovered patients approximately 5 months after undergoing COVID-19 (green, n = 14), and patients hospitalized with COVID-19 (yellow, n = 17). (G) Lymphocytes exhibit significantly increased deformation in hospitalized COVID-19 patients. (H) Young’s modulus of lymphocytes is significantly lower in COVID-19 patients compared with the healthy or recovered donors. Statistical comparisons were done using Kruskal-Wallis test with Dunn’s post hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
👁 Figure 4
Figure 4
The appearance of large monocytes in COVID-19 patients. Typical scatter plot of monocyte deformation versus cell size (cross-sectional area) of a healthy blood donor with no known viral infection (A) compared with a patient 4 months after undergoing COVID-19 (B) and a patient with COVID-19 in an intensive care unit (C) is given. (D) The images of cells marked by corresponding numbers in the scatter plots. (E) Kernel density estimate plots demonstrating the differences in cell size and deformation among the three donors (A–C). (F) The median monocyte cell volume is significantly elevated in hospitalized COVID-19 patients (yellow, n = 17) compared with healthy blood donors (gray, n = 24) and recovered patients (green, n = 14). (G) A significant increase is also observed in the SD of cell volume. Statistical comparisons were done using Kruskal-Wallis test with Dunn’s post hoc test; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
👁 Figure 5
Figure 5
Altered physical phenotype of neutrophils in the peripheral blood of COVID-19 patients. Typical scatter plot of neutrophil deformation versus cell size (cross-sectional area) of a healthy blood donor with no known viral infection (A) compared with a patient 4 months after undergoing COVID-19 (B) and a patient with COVID-19 in an intensive care unit (C) is given. (D) Images of neutrophils marked by corresponding numbers in the scatter plots. (E) Kernel density estimate plots demonstrating the differences in cell size and deformation among the three donors (A–C). (F) The median cross-sectional area and (G) median cell volume of neutrophils of patients hospitalized with COVID-19 (yellow, n = 17) are significantly higher than those of the healthy blood donors (gray, n = 24) and of recovered patients approximately 5 months after undergoing COVID-19 (green, n = 14). (H) Neutrophils exhibit increased deformability in hospitalized COVID-19 patients compared with the healthy cohort. (I) Young’s modulus of neutrophils of the three donor groups. (J) Young’s modulus of neutrophils in three patients measured at two time points: during COVID-19 and after recovery. Circle markers represent the median value, and error bars represent SD. Statistical comparisons for (F)–(I) were done using Kruskal-Wallis test with Dunn’s post hoc test and for (J) using linear mixed model analysis; ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.

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