Meta-analysis of COVID-19 Single-cell Studies Confirms Eight Key Immune Responses

Overview

Journal Sci Rep

Specialty Science

Date 2021 Oct 22

PMID 34675242

Citations 10

Authors

Manik Garg

Xu Li

Pablo Moreno

Irene Papatheodorou

Yuelong Shu

Alvis Brazma

Zhichao Miao

Affiliations

Soon will be listed here.

Abstract

Several single-cell RNA sequencing (scRNA-seq) studies analyzing immune response to COVID-19 infection have been recently published. Most of these studies have small sample sizes, which limits the conclusions that can be made with high confidence. By re-analyzing these data in a standardized manner, we validated 8 of the 20 published results across multiple datasets. In particular, we found a consistent decrease in T-cells with increasing COVID-19 infection severity, upregulation of type I Interferon signal pathways, presence of expanded B-cell clones in COVID-19 patients but no consistent trend in T-cell clonal expansion. Overall, our results show that the conclusions drawn from scRNA-seq data analysis of small cohorts of COVID-19 patients need to be treated with some caution.

Citing Articles

Meta-atlas of Juvenile and Adult Enteric Neuron scRNA-seq for Dataset Comparisons and Consensus on Transcriptomic Definitions of Enteric Neuron Subtypes.

Benthal J, May-Zhang A, Southard-Smith E bioRxiv. 2024; .

PMID: 39574584 PMC: 11580969. DOI: 10.1101/2024.10.31.621315.

Comprehensive single-cell atlas of the mouse retina.

Li J, Choi J, Cheng X, Ma J, Pema S, Sanes J iScience. 2024; 27(6):109916.

PMID: 38812536 PMC: 11134544. DOI: 10.1016/j.isci.2024.109916.

Bulk and Single-Cell RNA Sequencing Elucidate the Etiology of Severe COVID-19.

Huminiecki L Int J Mol Sci. 2024; 25(6).

PMID: 38542251 PMC: 10970417. DOI: 10.3390/ijms25063280.

Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Tomassetti S, Ciani L, Luzzi V, Gori L, Trigiani M, Giuntoli L Front Med (Lausanne). 2024; 11:1259570.

PMID: 38371516 PMC: 10869531. DOI: 10.3389/fmed.2024.1259570.

Comprehensive single-cell atlas of the mouse retina.

Li J, Choi J, Cheng X, Ma J, Pema S, Sanes J bioRxiv. 2024; .

PMID: 38328114 PMC: 10849744. DOI: 10.1101/2024.01.24.577060.

References

Ren X, Wen W, Fan X, Hou W, Su B, Cai P . COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell. 2021; 184(23):5838. PMC: 8582084. DOI: 10.1016/j.cell.2021.10.023. View

Moreno P, Huang N, Manning J, Mohammed S, Solovyev A, Polanski K . User-friendly, scalable tools and workflows for single-cell RNA-seq analysis. Nat Methods. 2021; 18(4):327-328. PMC: 8299072. DOI: 10.1038/s41592-021-01102-w. View

Wolf F, Angerer P, Theis F . SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 2018; 19(1):15. PMC: 5802054. DOI: 10.1186/s13059-017-1382-0. View

Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K . Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019; 16(12):1289-1296. PMC: 6884693. DOI: 10.1038/s41592-019-0619-0. View

He J, Cai S, Feng H, Cai B, Lin L, Mai Y . Single-cell analysis reveals bronchoalveolar epithelial dysfunction in COVID-19 patients. Protein Cell. 2020; 11(9):680-687. PMC: 7363016. DOI: 10.1007/s13238-020-00752-4. View

Barrett T, Wilhite S, Ledoux P, Evangelista C, Kim I, Tomashevsky M . NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2012; 41(Database issue):D991-5. PMC: 3531084. DOI: 10.1093/nar/gks1193. View

Becht E, McInnes L, Healy J, Dutertre C, Kwok I, Ng L . Dimensionality reduction for visualizing single-cell data using UMAP. Nat Biotechnol. 2018; . DOI: 10.1038/nbt.4314. View

Wang Y, Song F, Zhu J, Zhang S, Yang Y, Chen T . GSA: Genome Sequence Archive<sup/>. Genomics Proteomics Bioinformatics. 2017; 15(1):14-18. PMC: 5339404. DOI: 10.1016/j.gpb.2017.01.001. View

Wolock S, Lopez R, Klein A . Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data. Cell Syst. 2019; 8(4):281-291.e9. PMC: 6625319. DOI: 10.1016/j.cels.2018.11.005. View

10.

Wilk A, Rustagi A, Zhao N, Roque J, Martinez-Colon G, McKechnie J . A single-cell atlas of the peripheral immune response in patients with severe COVID-19. Nat Med. 2020; 26(7):1070-1076. PMC: 7382903. DOI: 10.1038/s41591-020-0944-y. View

11.

Finak G, McDavid A, Yajima M, Deng J, Gersuk V, Shalek A . MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 2015; 16:278. PMC: 4676162. DOI: 10.1186/s13059-015-0844-5. View

12.

Zhang J, Wang X, Xing X, Xu Z, Zhang C, Song J . Single-cell landscape of immunological responses in patients with COVID-19. Nat Immunol. 2020; 21(9):1107-1118. DOI: 10.1038/s41590-020-0762-x. View

13.

Miao Z, Moreno P, Huang N, Papatheodorou I, Brazma A, Teichmann S . Putative cell type discovery from single-cell gene expression data. Nat Methods. 2020; 17(6):621-628. DOI: 10.1038/s41592-020-0825-9. View

14.

Li F, Luo M, Zhou W, Li J, Jin X, Xu Z . Single cell RNA and immune repertoire profiling of COVID-19 patients reveal novel neutralizing antibody. Protein Cell. 2020; 12(10):751-755. PMC: 7686823. DOI: 10.1007/s13238-020-00807-6. View

15.

Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J . Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020; 26(6):842-844. DOI: 10.1038/s41591-020-0901-9. View

16.

Lee J, Park S, Jeong H, Ahn J, Choi S, Lee H . Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci Immunol. 2020; 5(49). PMC: 7402635. DOI: 10.1126/sciimmunol.abd1554. View

17.

Raudvere U, Kolberg L, Kuzmin I, Arak T, Adler P, Peterson H . g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucleic Acids Res. 2019; 47(W1):W191-W198. PMC: 6602461. DOI: 10.1093/nar/gkz369. View

18.

Amid C, Alako B, Kadhirvelu V, Burdett T, Burgin J, Fan J . The European Nucleotide Archive in 2019. Nucleic Acids Res. 2019; 48(D1):D70-D76. PMC: 7145635. DOI: 10.1093/nar/gkz1063. View

19.

Schulte-Schrepping J, Reusch N, Paclik D, Bassler K, Schlickeiser S, Zhang B . Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell. 2020; 182(6):1419-1440.e23. PMC: 7405822. DOI: 10.1016/j.cell.2020.08.001. View

20.

Chua R, Lukassen S, Trump S, Hennig B, Wendisch D, Pott F . COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis. Nat Biotechnol. 2020; 38(8):970-979. DOI: 10.1038/s41587-020-0602-4. View