Evidence map›Paper›PMID 39558820›Full record

ArticleJournal of extracellular vesicles2024

Extracellular vesicles containing SARS-CoV-2 proteins are associated with multi-organ dysfunction and worse outcomes in patients with severe COVID-19.

Diego de Miguel-Perez, Marisol Arroyo-Hernandez, Sabrina La Salvia, Muthukumar Gunasekaran, Edward M Pickering, Stephanie Avila, Etse Gebru, Eduardo Becerril-Vargas, Sergio Monraz-Perez, Kapil Saharia and 13 more

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Review
  2. Review
  3. Condensates on the Move: Midbody Remnants as Large, Translation-Competent Extracellular Vesicles.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Extracellular vesicles decoying across host immunity.Journal of leukocyte biology · 2025
    Review
  10. Review
  11. Article
  12. Article
  13. 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

23 authors.

Diego de Miguel-PerezCenter for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0002-2822-4466
Marisol Arroyo-HernandezThoracic Oncology Unit, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico.
Sabrina La SalviaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Muthukumar GunasekaranMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Edward M PickeringDivision of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Stephanie AvilaTransplant and Cellular Therapy Program, Department of Medicine, University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Etse GebruTransplant and Cellular Therapy Program, Department of Medicine, University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Eduardo Becerril-VargasNational Institute of Respiratory Diseases, Mexico City, Mexico.
Sergio Monraz-PerezNational Institute of Respiratory Diseases, Mexico City, Mexico.
Kapil SahariaInstitute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Alison GrazioliDepartment of Medicine, Program in Trauma, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Michael T McCurdyDivision of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-5319-0475
Matthew FriemanDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Lisa MiorinDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Alessandro RussoMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Andrés F CardonaInstitute for Research and Education, Luis Carlos Sarmiento Angulo Cancer Treatment and Research Center (CTIC), Bogotá, Colombia.
Adolfo García-SastreDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Sunjay KaushalMarlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Fred R HirschCenter for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Djordje AtanackovicTransplant and Cellular Therapy Program, Department of Medicine, University of Maryland School of Medicine and Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.
Susmita SahooCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0002-7279-1564
Oscar ArrietaThoracic Oncology Unit, Instituto Nacional de Cancerologia (INCan), Mexico City, Mexico.
Christian RolfoCenter for Thoracic Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Funding

NIAID Centers of Excellence for Influenza Research and Response: Universal Influenza Vaccine Research Activities75N93021C00014 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GARCIA-SASTRE, ADOLFO · 2021 to 2025
$62.6M
SARS-CoV adaptations through a Systems Biology Lens (SYBIL)U19AI135972 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Adolfo Garcia-Sastre · 2018 to 2026
$27.2M
Viral Immunity and VAccination (VIVA) Human Immunology Project Consortium (HIPC)U19AI168631 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ana Fernandez-Sesma · 2022 to 2026
$14.4M
Vulnerability of SARS- CoV-2 Infection in Lung Cancer Based on Serological Antibody AnalysesU54CA260560 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SHYR, YU · 2020 to 2024
$10.0M
Extracellular Vesicle-Encapsulated AAVs for Therapeutic Gene Delivery to the HeartR01HL148786 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Kiyotake Ishikawa, Susmita Sahoo · 2019 to 2026
$4.1M
Circulating Extracellular Vesicles in the Pathogenesis of Type 1 DiabetesR01DK125856 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI SAHOO, SUSMITA, VASAVADA, RUPANGI C · 2021 to 2024
$1.8M
Dysregulated Adenosine Methylation of mRNA as a Novel Mechanism of Heart FailureR01HL140469 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI SAHOO, SUSMITA · 2018 to 2021
$1.7M
CRIPT (Center for Research on Influenza Pathogenesis and Transmission)Evox Therapeutics, UKNCI NIH HHS U54 CA260560NCI-SERONET U54CA260560NHLBI NIH HHS R01 HL140469NHLBI NIH HHS R01 HL148786NIAID-funded Center of Excellence for Influenza Research and Response CEIRRNIAID NIH HHS 75N93021C00014NIAID NIH HHS U19 AI135972NIAID NIH HHS U19AI135972NIAID NIH HHS U19 AI168631NIAID NIH HHS U19AI168631NIDDK NIH HHS R01 DK125856NIH-NHLBI R01HL140469NIH-NHLBI R01HL148786
6 · The paper itself

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and has been related to more than 7 million deaths globally since 2019. The association of high levels of IL-6 with severe cases led to the early evaluation of the anti-IL6 inhibitor tocilizumab as a potential treatment, which unfortunately failed to improve survival in many trials. Moreover, little is known about the development of COVID-19 sequelae, and biomarkers are needed to understand and anticipate these processes. Because extracellular vesicles (EVs) play an important role in viral infection and immune response, they could potentially serve as predictive and prognostic biomarkers. We isolated EVs from 39 patients with severe COVID-19, from which 29 received tocilizumab and 10 were considered controls. Blood samples, which were collected at hospitalisation before treatment, at Day 7, and Day 15 during follow-up, were assessed by immunoblot for longitudinal expression of spike (S) and nucleocapsid (N) proteins. Dynamic expression was calculated and compared with clinicopathological and experimental variables. Expression of EV S was validated by immunogold and imaging flow-cytometry, revealing an enrichment in CD9+ EVs. As a result, decreasing expression of EV viral proteins was observed in patients treated with tocilizumab. Moreover, higher increase in EV S was observed in patients with lower antibody response, hyperfibrinogenemia, lower respiratory function, higher blood pressure and shorter outcomes. These findings lay the foundation for future studies characterizing the role of EVs in multiorgan assessment and identifying biomarkers in patients with severe COVID-19 and possible long COVID.

Indexed as

Antibodies, Monoclonal, HumanizedCOVID-19Extracellular VesiclesMultiple Organ FailureSARS-CoV-2AdultAgedBiomarkersCoronavirus Nucleocapsid ProteinsCOVID-19 Drug TreatmentFemaleHumansInterleukin-6MaleMiddle AgedPhosphoproteinsAntibodies, Monoclonal, HumanizedBiomarkersCoronavirus Nucleocapsid ProteinsInterleukin-6nucleocapsid phosphoprotein, SARS-CoV-2PhosphoproteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2tocilizumabbiomarkersCOVID‐19extracellular vesicleslong‐COVIDnucleocapsidspike proteintocilizumab

Identifiers

PMID39558820
PMCPMC11574309

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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.