Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
Human nasal wash RNA-Seq reveals distinct cell-specific innate immune responses in influenza versus SARS-CoV-2
Kevin M. Gao, … , Robert W. Finberg, Jennifer P. Wang
Kevin M. Gao, … , Robert W. Finberg, Jennifer P. Wang
Published October 7, 2021
Citation Information: JCI Insight. 2021;6(22):e152288. https://doi.org/10.1172/jci.insight.152288.
View: Text | PDF
Clinical Research and Public Health COVID-19 Infectious disease

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

  • Text
  • PDF
Abstract

BACKGROUND Influenza A virus (IAV) and SARS-CoV-2 are pandemic viruses causing millions of deaths, yet their clinical manifestations are distinctly different.METHODS With 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.Results Nasal 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.Conclusions Our 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.Funding Massachusetts 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

×

Figure 4

Epithelial cell–epithelial cell interactions are diminished while specific innate immune cell interactions are enhanced in COVID-19 compared with influenza.

Options: View larger image (or click on image) Download as PowerPoint
Epithelial cell–epithelial cell interactions are diminished while specif...
(A) Statistically significant receptor-ligand pair interactions between single cells across cell lineages were computed using CellPhoneDB. A multiple Mann-Whitney test was performed on cell lineage interactions for patients with COVID-19 (COV) and healthy controls (HCs), for COV and patients with influenza (FLU), and for FLU and HCs. Volcano plots show multiple statistical comparisons. Dots are annotated as a cell lineage pair X:Y, with X being the cell lineage expressing a receptor, and Y being the cell lineage expressing a ligand. The mean rank difference and adjusted P value are shown on the axes. (B–D) Significant receptor-ligand interactions are plotted across donor samples based on disease states. Composition and consistency of receptor-ligand interactions was assessed across disease states, with each heatmap row representing a receptor-ligand pair. (B) Epithelial cell–epithelial cell interactions diminished in frequency in COV vs. HC (differences ≥0.4). (C) Macrophage-macrophage interactions increased in COV vs. HC and in FLU vs. HC. (D) Macrophage-neutrophil interactions increased in COV vs. HC and in FLU vs. HC. Statistical significance for group-cell group interactions between patient samples across disease states (bar graphs) was determined by a Kruskal-Wallis test (*P < 0.05; **P < 0.01). Each heatmap column refers to the disease state, and the color represents the fraction of donors with statistical significance for annotated receptor-ligand interaction (CellPhoneDB analysis, P < 0.05). Note that for C and D, 1 HC donor sample did not have any macrophages or neutrophils, so interactions could not be reported. n = 5 for COV, n = 6 for HC, and n = 5 for FLU.

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts