Evidence map›Paper›PMID 33730024›Full record

ArticlePLoS biology2021

Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.

Neal G Ravindra, Mia Madel Alfajaro, Victor Gasque, Nicholas C Huston, Han Wan, Klara Szigeti-Buck, Yuki Yasumoto, Allison M Greaney, Victoria Habet, Ryan D Chow and 17 more

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 2 pooled it
19.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 2 syntheses or guidelines pooled it, 271 citations in OpenAlex.

  1. Single-cell RNA sequencing offers novel perspectives in viral infection research.Frontiers in cellular and infection microbiology · 2026
    Pooled it
  2. [Pulmonary innate immune response in Sars-cov-2 infection]Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2022
    Pooled it
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  12. Genetic and chemical correction of cystic fibrosis reduces airway susceptibility to SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2026
    Article
  13. Article
  14. Intrinsic OASL expression governs heterogeneity in interferon induction during influenza A virus infection.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 4 institutions in 2 countries.

Neal G RavindraCardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0001-5558-3758
Mia Madel AlfajaroDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.
Victor GasqueCardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0001-7505-305X
Nicholas C HustonDepartment of Molecular Biophysics & Biochemistry, Yale School of Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0002-7631-4095
Han WanDepartment of Molecular, Cellular, and Developmental Biology, Yale School of Medicine, New Haven, Connecticut, United States of America.
Klara Szigeti-BuckDepartment of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.
Yuki YasumotoDepartment of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0001-9882-4478
Allison M GreaneyDepartment of Biomedical Engineering, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0002-6316-0410
Victoria HabetDepartment of Pediatrics, Yale School of Medicine, New Haven, Connecticut, United States of America.
Ryan D ChowDepartment of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0002-1872-6307
Jennifer S ChenDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0002-7808-2670
Jin WeiDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0002-2832-1610
Renata B FillerDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.
Bao WangDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0002-6472-2307
Guilin WangYale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut, United States of America.
Laura E NiklasonDepartment of Biomedical Engineering, Yale University, New Haven, Connecticut, United States of America.
Ruth R MontgomeryDepartment of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0002-8661-4454
Stephanie C EisenbarthDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.
Sidi ChenDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.
Adam WilliamsThe Jackson Laboratory, Farmington, Connecticut, United States of America.
Akiko IwasakiDepartment of Immunobiology, Yale University, New Haven, Connecticut, United States of America.
Tamas L HorvathDepartment of Comparative Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.
Ellen F FoxmanDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0001-9767-9942
Richard W PierceDepartment of Pediatrics, Yale School of Medicine, New Haven, Connecticut, United States of America.
Anna Marie PyleDepartment of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.
David van DijkCardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School Medicine, New Haven, Connecticut, United States of America.ORCID 0000-0003-3911-9925
Craig B WilenDepartment of Laboratory Medicine, Yale University, New Haven, Connecticut, United States of America.ORCID 0000-0003-2495-9403
Yale University · USHoward Hughes Medical Institute · USJackson Laboratory · USUniversité Claude Bernard Lyon 1 · FR

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI David A. Hafler, RUTH R MONTGOMERY · 2010 to 2026
$50.4M
Predoctoral Training Program in VirologyT32AI055403 · NIAID · YALE UNIVERSITY · PI KUMAR, PRITI, MOTHES, WALTHER H · 2003 to 2024
$3.6M
Engineered Tracheal ReplacementsR01HL138540 · NHLBI · YALE UNIVERSITY · PI NIKLASON, LAURA E · 2017 to 2020
$2.5M
lncRNA Control of Airway Epithelial Cell Responses to Type 2 InflammationR01AI141609 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI WILLIAMS, ADAM · 2019 to 2022
$2.4M
Cell Death and Cross-Protection in Rhinovirus InfectionK08AI119139 · NIAID · YALE UNIVERSITY · PI FOXMAN, ELLEN FLESCHER · 2015 to 2019
$947k
Role of virus-receptor interactions in determining norovirus tropism and pathogenesis in vivoK08AI128043 · NIAID · YALE UNIVERSITY · PI WILEN, CRAIG BRIAN · 2017 to 2021
$940k
Mechanisms of Endothelial Cell Dysfunction in Critically Ill ChildrenK08HL136898 · NHLBI · YALE UNIVERSITY · PI PIERCE, RICHARD W · 2019 to 2023
$780k
The Function of lncRNAs in Airway Epithelial CellsR21AI133440 · NIAID · JACKSON LABORATORY · PI WILLIAMS, ADAM · 2018 to 2019
$520k
Mechanosensation in tumorigenesis and metastasisF30CA250249 · NCI · YALE UNIVERSITY · PI CHOW, RYAN D · 2020 to 2022
$113k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR001863NCI NIH HHS F30 CA250249NHLBI NIH HHS K08 HL136898NHLBI NIH HHS R01 HL138540NIAID NIH HHS K08 AI119139NIAID NIH HHS K08 AI128043NIAID NIH HHS R01 AI141609NIAID NIH HHS R21 AI133440NIAID NIH HHS T32 AI055403NIAID NIH HHS U19 AI089992Wellcome Trust
6 · The paper itself

Abstract

There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway.

Indexed as

Gene ExpressionAdultBronchiCells, CulturedCOVID-19EpitheliumHumansImmunity, InnateLongitudinal StudiesSARS-CoV-2Single-Cell AnalysisTranscriptomeViral Tropism

Identifiers

PMID33730024
PMCPMC8007021
OpenAlexW3137917350

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.