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. 2021 Sep 17;37(1):109793. doi: 10.1016/j.celrep.2021.109793

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© 2021 The Author(s)

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Heterogeneity analysis of COVID-19 patients illustrates a “three-stage” model associated with inflammatory signatures in monocytes

(A) A workflow schematic for the heterogeneity analysis of COVID-19 patients.

(B) UMAP embeddings of samples from COVID-19 patients, colored by cluster (top) and pseudostage (bottom). Pie plots within the top panel show the proportion of sample states for each cluster.

(C) Illustration of the proportion analysis of the ten hyperinflammatory cell subtypes in COVID-19 patients. Top, heatmap of cell-type proportions for each hyperinflammatory cell subtype in COVID-19 patients. The color bar above the heatmap indicates different clusters. Middle, heatmaps of the ordered pseudostage and corresponding inflammatory score in samples from COVID-19 patients. Bottom, boxplots of the cell proportion of each sample for these four subtypes (from left to right: T-CD4-LTB-S100A4, Mono-CD14-S100A8-RETN, Mono-CD14-S100A8-CD163, Mono-CD14-CCL3) from the indicated clusters (cluster 1, n = 93; cluster 2, n = 37; cluster 3, n = 27).

(D) Top, boxplots of the cell proportions of samples for each subtype (from left to right: Mono-CD14-CCL3, Mono-CD14-S100A8-RETN, Mono-CD14-S100A8-CD163) in different clusters (cluster 1, n = 8; cluster 2, n = 7; cluster 3, n = 21) from severe active patients. Bottom, boxplots of the signature scores of each subtype in different clusters from severe active patients.

(E) Diagram of biological pathways and genes enriched in samples of cluster 3 from severe active patients. Network edges represent gene-pathway associations, and edges of different pathways are indicated by different colors. The significance of the pathways is indicated by circle size. The color bar (from blue to red) represents fold change values in gene expression levels, p values were assessed by clusterProfiler’s built-in function “enrichGO” with default parameters.

In (C) and (D), statistical significance was evaluated with Student’s t test. The boxplots show the mean and interquartile range (IQR), with whiskers extending to 1.5 × IQR.