Human nasal wash RNA-Seq reveals distinct cell-specific innate immune responses in influenza versus SARS-CoV-2.

Abstract

BACKGROUNDInfluenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different.METHODSWith the hypothesis that upper airway immune and epithelial cell responses are also distinct, we performed single-cell RNA sequencing (scRNA-Seq) on nasal wash cells freshly collected from adults with either acute COVID-19 or influenza or from healthy controls. We focused on major cell types and subtypes in a subset of donor samples.ResultsNasal wash cells were enriched for macrophages and neutrophils for both individuals with influenza and those with COVID-19 compared with healthy controls. Hillock-like epithelial cells, M2-like macrophages, and age-dependent B cells were enriched in COVID-19 samples. A global decrease in IFN-associated transcripts in neutrophils, macrophages, and epithelial cells was apparent in COVID-19 samples compared with influenza samples. The innate immune response to SARS-CoV-2 appears to be maintained in macrophages, despite evidence for limited epithelial cell immune sensing. Cell-to-cell interaction analyses revealed a decrease in epithelial cell interactions in COVID-19 and highlighted differences in macrophage-macrophage interactions for COVID-19 and influenza.ConclusionsOur study demonstrates that scRNA-Seq can define host and viral transcriptional activity at the site of infection and reveal distinct local epithelial and immune cell responses for COVID-19 and influenza that may contribute to their divergent disease courses.FundingMassachusetts Consortium on Pathogen Readiness, the Mathers Foundation, and the Department of Defense (W81XWH2110029) "COVID-19 Expansion for AIRe Program."

• Authors: Kevin M Gao, Alan G Derr, Zhiru Guo, Kerstin Nündel, Ann Marshak-Rothstein, Robert W Finberg, Jennifer P Wang
• Journal: JCI insight (JCI Insight) Vol. 6 Issue 22 (11 22 2021) ISSN: 2379-3708 [Electronic] United States
• PMID: 34618691 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Topics

• Adult
• COVID-19 (genetics, immunology)
• Female
• Humans
• Immunity, Innate
• Influenza A virus (genetics, immunology)
• Influenza, Human (genetics, immunology)
• Macrophages (immunology, virology)
• Male
• Nasal Lavage
• RNA-Seq
• SARS-CoV-2 (genetics, immunology)