Acute COVID-19 cohort - peripheral blood mononuclear cells across disease severity and time

mononuclear phagocytes-MP CD14 IFI6

Full Name: IFN RNASE2/CLU+ CD14-positive, CD16-negative classical monocyte
Closest Ontology Term: CD14-positive, CD16-negative classical monocyteCL:0002057
Synonyms Terms that have the same, or nearly the same, meaning as the selected cell type.: MP-2, CD14 IFI6, ISG-high sepsis-associated monocyte, ISG-high MS1-like monocyte
Category Class of which the cell type is a subclass.: monocyteCL:0000576
Ontology Assessment Disagreements with any aspect of the Cell Ontology.: Proposed new term: an ISG-high variant of the sepsis-associated MS1 monocyte state (RNASE2 [0.78], CLU [0.69], MCEMP1 [0.62], RETN [0.61] with IFI6 [0.82], IFI27 [0.77], ISG15 [0.73] and low HLA-DR). Associated with COVID-19 severity and serum IL-6. A related name, 'IFN1 ALOX5AP+ CD14-positive, CD16-negative classical monocyte', has been proposed on CAP by another dataset; we did not reuse it because ALOX5AP is only weakly enriched here (ALOX5AP [0.55]). Suggested parent: CD14-positive, CD16-negative classical monocyte (CL:0002057). Numbers in brackets are one-vs-rest AUCs within the mononuclear phagocyte lineage.
Marker Gene Evidence Gene markers used by researcher to assign this cell annotation.: IFI6, S100A8, S100A9, RNASE2, IFI27, IFITM3, LY6E, ISG15, LGALS1, IFITM1, CD14
Canonical Marker Genes: CD14, LYZ, S100A8, S100A9, VCAN, FCN1
Negative Marker Genes Genes expected to be absent, or expressed at a notably low level, in these cells, and whose absence supports the assignment of this cell annotation.: MT-CO1
Rationale: Cluster 2 of the mononuclear phagocyte lineage (paper subset MP-2). Classical monocyte markers (CD14 [0.64], LYZ [0.66], S100A8 [0.79], S100A12 [0.71]) with high ISG expression (IFI6 [0.82], IFI27 [0.77], ISG15 [0.73]), low HLA class II (HLA-DRA [0.37]), and genes of the sepsis-associated MS1 state (RNASE2 [0.78], CLU [0.69], MCEMP1 [0.62], RETN [0.61]). The paper describes it as an ISG-high variant of the sepsis-associated state (MP-3). More abundant after infection and in severe disease, and associated with serum IL-6; its abundance fell over time with serum interferon levels. Numbers in brackets are one-vs-rest AUCs within the mononuclear phagocyte lineage.
Rationale DOI: 10.1101/2025.09.19.25334095 10.1038/s41591-020-0752-4 10.1126/scitranslmed.abe9599 10.1016/j.cell.2020.08.001 10.1016/j.cell.2022.01.012

Inherited from COVID_annotation_07062023

Set of Labels Description: Manual annotations of Leiden clusters computed separately within each of four lineages (B cells, CD4 T cells, CD8 T and NK cells, mononuclear phagocytes). For each lineage, PCA scores were aligned across batches with Harmony, each cell was connected to its 50 nearest neighbors, and the Leiden algorithm was run on that graph. Clusters were annotated by hand from marker genes (one-vs-rest AUC of 0.7 or more and pseudobulk FDR below 0.05), cross-referenced with published immune cell signatures and with CITE-seq surface protein data. Each label combines the lineage with the marker genes chosen when the labels were made; some subsets were renamed later in the paper, so the synonyms field lists the paper's subset ID (e.g., MP-12) and later name for each label. Cell Ontology terms were assigned in October 2026 from the marker statistics and the paper's interpretation of each subset.
Annotation Method: manual

mononuclear phagocytes-MP CD14 IFI6

Full Name

IFN RNASE2/CLU+ CD14-positive, CD16-negative classical monocyte

Closest Ontology Term

CD14-positive, CD16-negative classical monocyteCL:0002057

Synonyms

Terms that have the same, or nearly the same, meaning as the selected cell type.

MP-2, CD14 IFI6, ISG-high sepsis-associated monocyte, ISG-high MS1-like monocyte

Category

Class of which the cell type is a subclass.

monocyteCL:0000576

Ontology Assessment

Disagreements with any aspect of the Cell Ontology.

Proposed new term: an ISG-high variant of the sepsis-associated MS1 monocyte state (RNASE2 [0.78], CLU [0.69], MCEMP1 [0.62], RETN [0.61] with IFI6 [0.82], IFI27 [0.77], ISG15 [0.73] and low HLA-DR). Associated with COVID-19 severity and serum IL-6. A related name, 'IFN1 ALOX5AP+ CD14-positive, CD16-negative classical monocyte', has been proposed on CAP by another dataset; we did not reuse it because ALOX5AP is only weakly enriched here (ALOX5AP [0.55]). Suggested parent: CD14-positive, CD16-negative classical monocyte (CL:0002057). Numbers in brackets are one-vs-rest AUCs within the mononuclear phagocyte lineage.

Marker Gene Evidence

Gene markers used by researcher to assign this cell annotation.

IFI6, S100A8, S100A9, RNASE2, IFI27, IFITM3, LY6E, ISG15, LGALS1, IFITM1, CD14

Canonical Marker Genes

CD14, LYZ, S100A8, S100A9, VCAN, FCN1

Negative Marker Genes

Genes expected to be absent, or expressed at a notably low level, in these cells, and whose absence supports the assignment of this cell annotation.

MT-CO1

Rationale

Cluster 2 of the mononuclear phagocyte lineage (paper subset MP-2). Classical monocyte markers (CD14 [0.64], LYZ [0.66], S100A8 [0.79], S100A12 [0.71]) with high ISG expression (IFI6 [0.82], IFI27 [0.77], ISG15 [0.73]), low HLA class II (HLA-DRA [0.37]), and genes of the sepsis-associated MS1 state (RNASE2 [0.78], CLU [0.69], MCEMP1 [0.62], RETN [0.61]). The paper describes it as an ISG-high variant of the sepsis-associated state (MP-3). More abundant after infection and in severe disease, and associated with serum IL-6; its abundance fell over time with serum interferon levels. Numbers in brackets are one-vs-rest AUCs within the mononuclear phagocyte lineage.

Rationale DOI

10.1101/2025.09.19.25334095 10.1038/s41591-020-0752-4 10.1126/scitranslmed.abe9599 10.1016/j.cell.2020.08.001 10.1016/j.cell.2022.01.012

Inherited from COVID_annotation_07062023

Set of Labels Description

Manual annotations of Leiden clusters computed separately within each of four lineages (B cells, CD4 T cells, CD8 T and NK cells, mononuclear phagocytes). For each lineage, PCA scores were aligned across batches with Harmony, each cell was connected to its 50 nearest neighbors, and the Leiden algorithm was run on that graph. Clusters were annotated by hand from marker genes (one-vs-rest AUC of 0.7 or more and pseudobulk FDR below 0.05), cross-referenced with published immune cell signatures and with CITE-seq surface protein data. Each label combines the lineage with the marker genes chosen when the labels were made; some subsets were renamed later in the paper, so the synonyms field lists the paper's subset ID (e.g., MP-12) and later name for each label. Cell Ontology terms were assigned in October 2026 from the marker statistics and the paper's interpretation of each subset.

Annotation Method

manual