Evidence map›Paper›PMID 33431511›Full record

ArticleScience translational medicine2021

Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys.

Emily Speranza, Brandi N Williamson, Friederike Feldmann, Gail L Sturdevant, Lizzette Pérez-Pérez, Kimberly Meade-White, Brian J Smith, Jamie Lovaglio, Craig Martens, Vincent J Munster and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed, 3 pooled it
11.2field-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

129 citing papers in PubMed, 3 syntheses or guidelines pooled it, 182 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. A Meta-Analysis of Rhesus Macaques (Comparative medicine · 2021
    Pooled it
  4. Article
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  8. Extra gene coding capacity of SARS-CoV-2 provides a virus engineering platform for in vitro and in vivo applications.Proceedings of the National Academy of Sciences of the United States of America · 2026
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69 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Emily SperanzaLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0003-0666-4804
Brandi N WilliamsonLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Friederike FeldmannRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0002-1363-1077
Gail L SturdevantLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0001-9653-9008
Lizzette Pérez-PérezLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0001-5881-4363
Kimberly Meade-WhiteLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0003-0503-8174
Brian J SmithRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Jamie LovaglioRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Craig MartensResearch Technologies Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Vincent J MunsterLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0002-2288-3196
Atsushi OkumuraLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0002-7779-3059
Carl ShaiaRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0001-8907-8821
Heinz FeldmannLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0001-9448-8227
Sonja M BestLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.ORCID 0000-0003-0206-297X
Emmie de WitLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. emmie.dewit@nih.gov.ORCID 0000-0002-9763-7758
National Institutes of Health · USNational Institute of Allergy and Infectious Diseases · US

Funding

Infectious Diseases Research Technologies Core - RMLZICAI001052 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI CHERRY, JAMES · 2009 to 2025
$133.3M
Virus-Host Interactions: Induction and Evasion of Host Innate ImmunityZIAAI001125 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BEST, SONJA · 2010 to 2025
$28.1M
Emerging respiratory viruses - pathogenesis and countermeasuresZIAAI001259 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DE WIT, EMMIE · 2020 to 2025
$10.1M
SARS-CoV-2: Pathogenesis and Countermeasure DevelopmentZIAAI001300 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FELDMANN, HEINRICH · 2020 to 2023
$3.3M
Mechanisms of immunopathology of COVID-19/ARDS, and strategies to mitigate detrimental inflammatory responsesZIAAI001292 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BEST, SONJA · 2020 to 2025
$2.4M
SARS-CoV-2 pathogenesis and countermeasures ZIAAI001288 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DE WIT, EMMIE · 2020 to 2023
$576k
6 · The paper itself

Abstract

Detailed knowledge about the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is important for uncovering the viral and host factors that contribute to coronavirus disease 2019 (COVID-19) pathogenesis. Old-World nonhuman primates recapitulate mild to moderate cases of COVID-19, thereby serving as important pathogenesis models. We compared African green monkeys inoculated with infectious SARS-CoV-2 or irradiated, inactivated virus to study the dynamics of virus replication throughout the respiratory tract. Genomic RNA from the animals inoculated with the irradiated virus was found to be highly stable, whereas subgenomic RNA, an indicator of viral replication, was found to degrade quickly. We combined this information with single-cell RNA sequencing of cells isolated from the lung and lung-draining mediastinal lymph nodes and developed new analysis methods for unbiased targeting of important cells in the host response to SARS-CoV-2 infection. Through detection of reads to the viral genome, we were able to determine that replication of the virus in the lungs appeared to occur mainly in pneumocytes, whereas macrophages drove the inflammatory response. Monocyte-derived macrophages recruited to the lungs, rather than tissue-resident alveolar macrophages, were most likely to be responsible for phagocytosis of infected cells and cellular debris early in infection, with their roles switching during clearance of infection. Together, our dataset provides a detailed view of the dynamics of virus replication and host responses over the course of mild COVID-19 and serves as a valuable resource to identify therapeutic targets.

Indexed as

Sequence Analysis, RNASingle-Cell AnalysisAlveolar Epithelial CellsAnimalsBronchoalveolar Lavage FluidChlorocebus aethiopsCOVID-19DNA, ViralFemaleGenome, ViralInflammationLungLymph NodesMacrophagesMaleMediastinumDNA, Viral

Identifiers

PMID33431511
PMCPMC7875333
OpenAlexW3120709764

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.