Evidence map›Paper›PMID 34452463›Full record

ArticleViruses2021

Longitudinal Assessment of Cytokine Expression and Plasminogen Activation in Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction in End-Stage Disease.

Peter Simons, Yan Guo, Virginie Bondu, Susan L Tigert, Michelle Harkins, Samuel Goodfellow, Cana Tompkins, Devon Chabot-Richards, Xuexian O Yang, Laura Gonzalez Bosc and 3 more

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

Article in Viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 42% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
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

13 authors at 2 institutions in 1 country.

Peter SimonsDepartment of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Yan GuoBioinformatics Shared Resource Center, Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.ORCID 0000-0001-5252-3960
Virginie BonduDepartment of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Susan L TigertClinical and Translational Science Center (CTSC), University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Michelle HarkinsDivision of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Samuel GoodfellowDivision of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.ORCID 0000-0003-0471-8303
Cana TompkinsDepartment of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Devon Chabot-RichardsDepartment of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.ORCID 0000-0002-6437-8438
Xuexian O YangMolecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.ORCID 0000-0001-6816-7024
Laura Gonzalez BoscVascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.ORCID 0000-0001-7505-4909
Steven BradfuteDivision of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Daniel A LawrenceDivision of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Tione BurandaDepartment of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
University of New Mexico · USUniversity of Michigan · US

Funding

Unraveling the role of tPA in the neurovascular unitR01HL055374 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI David Antonetti, Daniel A Lawrence · 1995 to 2026
$8.6M
Biology of Infectious Diseases &InflammationT32AI007538 · NIAID · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Michelle A Ozbun · 1998 to 2026
$5.2M
The Cytokine Suppressor CIS in Giant Cell PneumonitisR01HL148337 · NHLBI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI YANG, XUEXIAN · 2020 to 2023
$1.5M
NHLBI NIH HHS R01 HL055374NHLBI NIH HHS R01 HL148337NIAID NIH HHS T32 AI007538
6 · The paper itself

Abstract

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We measured viral load, levels of various cytokines, urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1). We found significantly elevated levels of proinflammatory cytokines and PAI-1 in five end-stage cases. There was no difference between the expression of active uPA in survivors' and decedents' cases. However, total uPA in decedents' cases was significantly higher compared to survivors'. In some end-stage cases, uPA was refractory to PAI-1 inhibition as measured by zymography, where uPA and PAI-1 were strongly correlated to lymphocyte counts and IFN-γ. We also found bacterial co-infection influencing the etiology and outcome of immune response in two cases. Unsupervised Principal Component Analysis and hierarchical cluster analyses resolved separate waves of correlated immune mediators expressed in one case patient due to a sequential co-infection of bacteria and SNV. Overall, a robust proinflammatory immune response, characterized by an imbalance in T helper 17 (Th17) and regulatory T-cells (Treg) subsets, was correlated with dysregulated inflammation and mortality. Our sample size is small; however, the core differences correlated to survivors and end-stage HCPS are instructive.

Indexed as

AdolescentAdultCoinfectionCytokinesFemaleHantavirus InfectionsHantavirus Pulmonary SyndromeHumansInflammationLongitudinal StudiesLungMaleMiddle AgedPatient AcuityPlasminogenRetrospective StudiesCytokinesPlasminogencell barrier functionco-infectioncorrelationcytokinesECMOhantavirusorthohantavirusPAI-1pathogenesisplasminogen activationprincipal component analysisuPA

Identifiers

PMID34452463
PMCPMC8402847
OpenAlexW3187735116

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.