Single-Cell Study Unveils Immune Response to COVID-19
Summary
Although a complete understanding of the relevant immune cells is still lacking, a malfunctioning immune response is a common motif in patients with coronavirus disease 2019 (COVID-19), which affects symptoms and mortality. They generated a comprehensive immune landscape with 1.46 million cells by sequencing the RNA of individual cells in 284 samples from 196 COVID-19 patients and controls. They were able to ascertain that various peripheral immune subtype changes are associated with multiple clinical aspects of COVID-19 due to the size of the dataset. Age, gender, disease stage, and severity are some characteristics. Significant transcriptome changes were found in virus-positive cells in addition to the discovery of RNA from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was found in a number of immunological and epithelial cell types. The frequent cytokine storms observed in patients with severe disease may be caused by the systemic overexpression of S100A8/A9, primarily carried out by megakaryocytes and monocytes in the peripheral circulation. For the study of the pathogenesis of COVID-19 and the creation of suitable therapeutic options, the data they have gathered is an invaluable resource.
Fig.1 Graphical abstract. (Ren, 2021)
Research Criteria
They obtained scRNA-seq data for a cohort of 196 individuals, including hospitalized COVID-19 patients with moderate or severe disease and patients in the convalescent stage, as well as healthy controls. They revealed that SARS-CoV-2 RNA could be detected in a wide range of cell types and observed critical changes in COVID-19 clinical features.
Fig.2 Experimental design. (Ren, 2021)
Sample Type
Human PBMCs samples; Sorted B/T cells or both; Human lung tissues; Human sputum samples.
Result—Integrated Analysis of COVID-19 scRNA-Seq Data
In the end, 1,462,702 single cells of superior quality were obtained. In addition, 64 cell clusters were produced, representing various types of respiratory and peripheral blood cells. Notable discrepancies could be noticed based on the tSNE projection. The tissue preference of each cluster was displayed based on RO/E, which is the ratio of observed to randomly expected cell numbers utilized to eliminate the technical variances in tissue preference estimation. Notably, the BALF (bronchoalveolar lavage fluid) increased the concentration of growing CD8+ and CD4+ T and B cells more than PBMCs. Similarly, the preference of each cluster in distinct patient groups was demonstrated, with proliferative and activated B and T cells and macrophages being more prevalent in severe COVID-19 patients at the disease progression stage.
Fig.3 Multi-tissue and multi-stage single-cell atlas of COVID-19 patients and healthy controls. (Ren, 2021)
Result—SARS-CoV-2 RNAs Detected in Multiple Epithelial and Immune Cell Types
From the six BALF and two sputum samples of severe COVID-19 patients at the illness progression stage, they discovered viral RNAs of SARS-CoV-2 in cells from ciliated, secretory, and squamous epithelial cells and a wide range of immune cells. The associated marker genes validated the identity of these SARS-CoV-2 RNA-positive cells. Although type II alveolar (AT2) cells were susceptible to SARS-CoV-2 infection, their study revealed few AT2 cells in the BALF and no detectable SARS-CoV-2 RNA in AT2 cells, consistent with the notion that cells from the lower respiratory tract were less likely to be infected than those from the nasal and upper respiratory tract.
Fig.4 Cell types with SARS-CoV-2 RNA detected. (Ren, 2021)
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Reference
- Ren, X.; et al. COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas. Cell. 2021, 184(7): 1895-1913.
