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

mononuclear phagocytes-MP S100A8 ALOX5AP

Full Name: ALOX5AP+ 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-3, CD14 CLU, MS1, CD14 monocyte state 1, sepsis-associated monocyte, HLA-DR-low S100A-high monocyte
Category Class of which the cell type is a subclass.: monocyteCL:0000576
Ontology Assessment Disagreements with any aspect of the Cell Ontology.: Same name as a term already proposed on CAP by another blood dataset, whose markers (ALOX5AP, MCEMP1, PADI4, RETN, RNASE2) match the MS1 sepsis-associated monocyte signature (Reyes et al. 2020). CL has no term for this state. CL does have 'myeloid suppressor cell' (CL:0000889), but that is defined by function, which was not tested here. Suggested parent: CD14-positive, CD16-negative classical monocyte (CL:0002057).
Marker Gene Evidence Gene markers used by researcher to assign this cell annotation.: S100A8, S100A9, S100A12, TSPO, CTSD, LGALS1, RPLP1, VCAN, ALOX5AP, PLBD1
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.: CD74, FTH1, HLA-DRA, HLA-DRB1, B2M
Rationale: Cluster 3 of the mononuclear phagocyte lineage (paper subset MP-3). Sepsis-associated monocyte state 1 (MS1): S100A8 [0.86], S100A9 [0.85], S100A12 [0.84], ALOX5AP [0.66], RETN [0.66], MCEMP1 [0.66], PADI4 [0.63], CLU [0.62], with low HLA class II (HLA-DRA [0.23], CD74 [0.20]). Matches the CD14 HLA-DR-low S100A-high MS1 state first described in bacterial sepsis, also described as myeloid-derived suppressor cells. More abundant in severe COVID-19 and increased with serum IL-6; cells mapping to this state were no longer detectable after tocilizumab treatment. Name reuses a term already proposed on CAP by another blood dataset, so the two can be compared. 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

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 S100A8 ALOX5AP

Full Name

ALOX5AP+ 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-3, CD14 CLU, MS1, CD14 monocyte state 1, sepsis-associated monocyte, HLA-DR-low S100A-high monocyte

Category

Class of which the cell type is a subclass.

monocyteCL:0000576

Ontology Assessment

Disagreements with any aspect of the Cell Ontology.

Same name as a term already proposed on CAP by another blood dataset, whose markers (ALOX5AP, MCEMP1, PADI4, RETN, RNASE2) match the MS1 sepsis-associated monocyte signature (Reyes et al. 2020). CL has no term for this state. CL does have 'myeloid suppressor cell' (CL:0000889), but that is defined by function, which was not tested here. Suggested parent: CD14-positive, CD16-negative classical monocyte (CL:0002057).

Marker Gene Evidence

Gene markers used by researcher to assign this cell annotation.

S100A8, S100A9, S100A12, TSPO, CTSD, LGALS1, RPLP1, VCAN, ALOX5AP, PLBD1

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.

CD74, FTH1, HLA-DRA, HLA-DRB1, B2M

Rationale

Cluster 3 of the mononuclear phagocyte lineage (paper subset MP-3). Sepsis-associated monocyte state 1 (MS1): S100A8 [0.86], S100A9 [0.85], S100A12 [0.84], ALOX5AP [0.66], RETN [0.66], MCEMP1 [0.66], PADI4 [0.63], CLU [0.62], with low HLA class II (HLA-DRA [0.23], CD74 [0.20]). Matches the CD14 HLA-DR-low S100A-high MS1 state first described in bacterial sepsis, also described as myeloid-derived suppressor cells. More abundant in severe COVID-19 and increased with serum IL-6; cells mapping to this state were no longer detectable after tocilizumab treatment. Name reuses a term already proposed on CAP by another blood dataset, so the two can be compared. 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

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