Evidence map›Paper›PMID 36334378›Full record

ArticleRedox biology2022

SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia.

Stephen L Archer, Asish Dasgupta, Kuang-Hueih Chen, Danchen Wu, Kaushal Baid, John E Mamatis, Victoria Gonzalez, Austin Read, Rachel Et Bentley, Ashley Y Martin and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

30 citing papers in PubMed, 54 citations in OpenAlex.

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  9. Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 1 country.

Stephen L ArcherDepartment of Medicine, Queen's University, Kingston, ON, Canada; Queen's Cardiopulmonary Unit (QCPU), Queen's University, Kingston, ON, Canada. Electronic address: stephen.archer@queensu.ca.
Asish DasguptaDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Kuang-Hueih ChenDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Danchen WuDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Kaushal BaidVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada.
John E MamatisDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Victoria GonzalezVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan; Saskatoon, SK, Canada.
Austin ReadDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Rachel Et BentleyDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Ashley Y MartinDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Jeffrey D MewburnDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Kimberly J Dunham-SnaryDepartment of Medicine, Queen's University, Kingston, ON, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Gerald A EvansDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Gary LevyUniversity of Toronto, Toronto, ON, Canada.
Oliver JonesQueen's Cardiopulmonary Unit (QCPU), Queen's University, Kingston, ON, Canada.
Ruaa Al-QazaziDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Brooke RingQueen's Cardiopulmonary Unit (QCPU), Queen's University, Kingston, ON, Canada.
Elahe AlizadehQueen's Cardiopulmonary Unit (QCPU), Queen's University, Kingston, ON, Canada.
Charles Ct HindmarchQueen's Cardiopulmonary Unit (QCPU), Queen's University, Kingston, ON, Canada.
Jenna RossiDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Patricia DA LimaQueen's Cardiopulmonary Unit (QCPU), Queen's University, Kingston, ON, Canada.
Darryl FalzaranoVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan; Saskatoon, SK, Canada.
Arinjay BanerjeeVaccine and Infectious Disease Organization, University of Saskatchewan, Saskatoon, SK, Canada; Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan; Saskatoon, SK, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Biology, University of Waterloo; Waterloo, ON, Canada.
Che C ColpittsDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Queen's University · CASaskatoon Medical Imaging · CAUniversity of Saskatchewan · CAUniversity of Toronto · CA

Funding

O2 sensing in the human and rabbit ductus arteriosus.R01HL071115 · NHLBI · UNIVERSITY OF CHICAGO · PI ARCHER, STEPHEN L · 2004 to 2015
$3.1M
Impaired mitochondrial fusion in pulmonary arterial hypertensionRC1HL099462 · NHLBI · UNIVERSITY OF CHICAGO · PI ARCHER, STEPHEN L · 2009 to 2010
$1.0M
CIHRNHLBI NIH HHS R01 HL071115NHLBI NIH HHS RC1 HL099462
6 · The paper itself

Abstract

rationaleSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively.

objectivesWe examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV.

methodsWe used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay.

resultsSARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpO

conclusionsCoronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

Indexed as

COVID-19Papillomavirus InfectionsAdenosine TriphosphateAnimalsHumansHypoxiaMiceMitochondrial Permeability Transition PoreSARS-CoV-2Adenosine TriphosphateMitochondrial Permeability Transition PoreApoptosisApoptosis inducing factor (AIF)Dynamin related protein 1 (Drp1)HCoV-OC43Hypoxic pulmonary vasoconstrictionMitochondrial fissionMitochondrial permeability transition pore (mPTP)Murine hepatitis virus (MHV-1)

Identifiers

PMID36334378
PMCPMC9558649
OpenAlexW4306146012

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.