Table 3.
Summary of Identified Immune Cell Subsets, Cytokines, and Gene Expression Upregulation in Comparison with Healthy Controls.a
Authors | Phase of Infection | Sample Type Technique | Immune Cell Subset, Cytokines, and Gene Expression |
---|---|---|---|
Giamarellos-Bourboulis et al.61 | Acute | Blood ELISA |
CD4+ T cells (IL-6 and IFNγ^) CD14 monocytes (IL-6) |
Wei et al.62 | Acute | Blood ELISA |
Monocytes (TNF and IL-1β)^ |
Huang et al.63 | Acute | Blood ELISA |
Laboratory findings on cytokine levels: IL-1B, IL-1RA, IL-7, IL-8, IL-9, IL-10, basic FGF, G-CSF, GM-CSF, IFNγ, IP10, CCL2, CCL3, CCL4, PDGF, TNFα, and VEGF Laboratory findings on cytokine levels (in ICU patients compared with non-ICU patients): IL-2, IL-7, IL-10, G-CSF, IP10, CCL2, CCL3, and TNFα |
Ni et al.67 | Convalescent | Blood ELISPOT |
NP-specific T cells RBD of S protein-specific T cells (IFNγ secretion increased in convalescent patients) |
Shi et al.74 | Acute | Blood flow cytometry |
CD3+CD8+ T cells* CD3+CD4+ T cells* (IL-2, IL-4, IL-6, and TNFα) CD3+CD4+CD25+CD127– Treg cells (IL-10) CD3–CD19+ B cells* CD3–CD16+CD56+ NK cells* |
Qin et al.71 | Acute | Blood flow cytometry |
CD3+CD4+ T cells* CD3+CD8+ T cells* CD45RA+CD3+CD4+CD25+CD127lo naïve Treg cells* CD3+CD4+CD25+CD127lo Treg cells* CD45RO+CD3+CD4+CD25+CD127lo induced Treg cells* CD3+CD19– B cells* Laboratory findings on cytokine levels: IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, IFNγ |
Thevarajan et al.72 | Acute | Blood flow cytometry |
CD38+HLA-DR+CD8+ T cells (granzyme A, granzyme B, and perforin) CD38+HLA-DR+CD4+ T cells CD4+CXCR5+ICOS+PD1+ follicular T cells CD3–CD19+CD27hiCD38hi antibody-secreting cells CD16+CD14+ monocytes* |
Xu et al.106 | Patient deceased | Blood flow cytometry |
CD38+HLA-DR+CD4+ T cells CCR6+CD4+ Th17 cells CD38+HLA-DR+CD8+ T cells (perforin and granulysin) |
Braun et al.76 | Acute | Blood flow cytometry |
CD38+HLA-DR+CD8+ T cells CD4+CD40L+CD137+ T cells CD38+HLA-DR+CD4+Ki-67+ T cells |
Weiskopf et al.75 | Acute | Blood flow cytometry |
CD45RA+CCR7+ naïve T cells CD45RA–CCR7– effector memory T cells CD45RA+CCR7– terminally differentiated effector T cells CD45RA–CCR7+ central memory T cells Activated CD4+ and CD8+ T cells = CD69+CD137+ Cytometric bead assay: IFNγ, TNFα, IL-2, IL-5, IL-13, IL-9, IL-10, and IL-22 |
Grifoni et al.77 | Convalescent | Blood flow cytometry |
OX40+CD137+CD4+ T cells (IL-2 and IFNγ) CD69+CD137+CD8+ T cells (IFNγ, TNFα, and granzyme B) |
Zhou et al.78 | Acute | Blood flow cytometry |
CD69+CD38+CD44+OX40+CD4+ T cells (IL-6, GM-CSF, and IFNγ) CD69+CD38+CD44+CD137+CD8+ T cells (GM-CSF) PD-1+Tim-3+CD4+ T cells PD-1+Tim-3+CD8+ T cells CD16+CD14+ monocytes (IL-6 and GM-CSF) |
Diao et al.79 | Acute | Blood flow cytometry |
PD-1+Tim-3+CD4+ T cells PD-1+Tim-3+CD8+ T cells Laboratory findings on cytokine levels: TNFα, IL-6, and IL-10 |
Zheng et al.80 | Acute | Blood flow cytometry |
NKG2A+CD8+ T cells (reduced secretion of CD107a, IFNγ, IL-2, and granzyme B) NKG2A+ NK cells (reduced secretion of CD107a, IFNγ, IL-2, granzyme B, and TNFα) |
Ouyang et al.81 | Acute | Blood CyTOF |
CD4+ T cells* CD8+ T cells* |
Leng et al.83 | Acute | Blood CyTOF |
CXCR3+CD4+ T cells CXCR+CD8+ T cells CXCR3+ NK cells |
Wang et al.82 | Acute | Blood CyTOF |
CD4+CD8+ T cells Naïve CD4+ T cells TGFβ+CD28– naïve CD4+ T cells Dendritic cells, macrophages, CD4+ T cells, and TGFβ+CD28– naïve CD8+ T cells^ Myeloid-derived suppressor cells (TGFβ, IL-10) |
Liao et al.85 | Acute | Lung BALF scRNAseq |
CCR7+ central memory T cells ZNF683+CD8+ T cells FCN1hi macrophages (S100A8, FCN, and CD14) FCN1loSPP1+ macrophages (CCL2, CCL3, and CXCL10) SPP1+ macrophages (A2M, GPR183, and CCL13) FABP4+ macrophages (FABP4, APOC1, and MARCO) Upregulated expression of IL1B, IL6, TNF, CCL2, CCL3, CCL4, CCL7, CXCL9, CXCL10, CXCL11, GZMA, GZMK, and FASLG Cytometric bead assay: IL-6, IL-8, and IL-1β |
Wen et al.87 | Convalescent | Blood scRNAseq |
CD3E+CD4+ naïve T cells (CCR7, LEF1, and TCF7) CCR7+CD3E+CD4+ central memory T cells (AQP3 and CD69) CD3E+CD4+ effector memory T cells (CCR6, CXCR6, CCL5, and PRDM1) FOXP3+CD3E+CD4+ Treg cells High expression of FOS, JUN, KLF6, S100A8, and IL1B CD8+ naïve T cells (CCR7, LEF1, and TCF7) CD8+ Tc cells (GZMB, GNLY, and PRF1) CD8+ effector memory T cells (GZMK)* TYMS+MKI67+CD8+ proliferating T cells M-CSF, GM-CSF, IFNg, and IL-1β Naïve B cells (CD19, CD20, IL4R, TCL1A, IGHD, and IGHM) Memory B cells (CD27, CD38, and IGHG) Immature B cells (CD19 and CD20) Plasma cells (XBP1 and MZB1) IL-6, LTA, and LTB IGHV3–7, IGHV3–15, IGHV3–21, IGHV3–23, and IGHV3–30 IGKV1–17, IGKV2–28, and IGKV3–15 IGLV1–44, IGLV2–8, and IGLV3–27 CD14+IL-1β+ monocytes (IL1B, JUN, FOS, JUNB, and KLF6) CD56hiCD16lo NK cells* CD56loCD16hi NK cells* |
The asterisk (*) indicates lower compared with healthy controls. The caret (^) indicates lower compared with non-ICU/nonsevere patients. hi, high; lo, low.