COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas

Abstract

Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes were associated with distinct clinical features including age, sex, severity, and disease stages of COVID-19. SARS-CoV-2 RNAs were found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within viral positive cells. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and developing effective therapeutic strategies for COVID-19.

Circulating Calprotectin as a Biomarker of COVID-19 Severity

“…Virus RNA was found in epithelial and immune cells leading to systemic upregulation of calprotectin potentially contributing to the mechanisms observed in severe COVID-19 patients. This data might indicated that calprotectin can function as a mechanistic biomarker and fit into the concept of precision medicine [135].…”

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping

“…A prerequisite for the virus to affect karyopherin-mediated nuclear translocation and therefore JAK-STAT signaling is viral entry into CD8 + T cells, and the ability to enter immune cells has recently been demonstrated for SARS-CoV-2 56 . We could not detect viral RNA in our scRNA-seq data using Viral-Track 57 .…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…Viral pathogens depend on the cellular machinery to propagate. Thus, it is evident that both HIV-1 and SARS-CoV-2 redirect large parts of the cell-intrinsic biological processes for their opportunistic use involving several thousands of genes and proteins [41,[136][137][138][139][140]. While the complex network of interactions between these viruses and their host cells has only been disentangled rudimentarily, the viral strategies of exploiting cellular components and programs appear manifold in both HIV-1 and SARS-CoV-2 infection.…”

“…Similar to HIV-1, SARS-CoV-2 profoundly interacts and modifies the cellular physiology both on the transcriptional [138][139][140][141][142] and protein level [99,139,143,144]. Host responses to SARS-CoV-2 vary substantially depending on viral load and infection stage as well as age and sex of the host [141].…”

“…However, when macrophages are highly activated, these cells can produce large amounts of cytokines (cytokine storm) that generate systemic hyperinflammation [428]. Megakaryocytes and monocyte subsets are critical peripheral sources of cytokine storms, which involves interactions of hyper-inflammatory cell subtypes in lung and peripheral blood [138]. The activation of macrophages is called macrophage activation syndrome (MAS) [428], and MAS-like severe inflammation and fibrinolysis are involved in COVID-19-associated pneumonia [429,430].…”