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Cited by 23COVID-19 Clinical Research StudiesNeutrophil, Myeloperoxidase and Oxidative MechanismsComplement system in diseases

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Systemic Inflammation and Complement Activation Parameters Predict Clinical Outcome of Severe SARS-CoV-2 Infections

Open access
Huber, Silke, Massri, Mariam, Grasse, Marco, Fleischer, Verena, Kellnerová, Sára, Harpf, Verena, Knabl, Ludwig, Knabl, Ludwig, Heiner, Tatjana, Kummann, Moritz, Neurauter, Magdalena, Rambach, Günter, Speth, Cornelia, Würzner, Reinhard·2021·Viruses
DOI 10.3390/v13122376PMC PMC8707937
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Abstract

Overactivation of the complement system has been characterized in severe COVID-19 cases. Complement components are known to trigger NETosis via the coagulation cascade and have also been reported in human tracheobronchial epithelial cells. In this longitudinal study, we investigated systemic and local complement activation and NETosis in COVID-19 patients that underwent mechanical ventilation. Results confirmed significantly higher baseline levels of serum C5a (24.5 ± 39.0 ng/mL) and TCC (11.03 ± 8.52 µg/mL) in patients compared to healthy controls (p < 0.01 and p < 0.0001, respectively). Furthermore, systemic NETosis was significantly augmented in patients (5.87 (±3.71) × 106 neutrophils/mL) compared to healthy controls (0.82 (±0.74) × 106 neutrophils/mL) (p < 0.0001). In tracheal fluid, baseline TCC levels but not C5a and NETosis, were significantly higher in patients. Kinetic studies of systemic complement activation revealed markedly higher levels of TCC and CRP in nonsurvivors compared to survivors. In contrast, kinetic studies showed decreased local NETosis in tracheal fluid but comparable local complement activation in nonsurvivors compared to survivors. Systemic TCC and NETosis were significantly correlated with inflammation and coagulation markers. We propose that a ratio comprising systemic inflammation, complement activation, and chest X-ray score could be rendered as a predictive parameter of patient outcome in severe SARS-CoV-2 infections.

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Crossref · 10.3390/v13122376

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  • SARS-CoV-2 infection strongly activates complement and other innate immune pathways such as TLR4 and the inflammasome, leading to increased IL-1β and IL-18 levels.

    “SARS-CoV-2 infection has been documented to strongly activate complement and to activate other innate immune pathways such as TLR4 and the inflammasome, which leads to increased IL-1 β and IL-18 levels. 137-142”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [138]

    The Discussion (page not provided) reports significantly higher complement activation products C5a and TCC in COVID-19 patients than in controls, supporting the complement portion of the claim. The passages do not address TLR4 or inflammasome activation, or an ensuing increase in IL-1β and IL-18. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Other key innate cytokines elevated during COVID-19 include TNFα and IL-6, which is increased by IL-1β.

    “Other key innate cytokines that are elevated during COVID-19 include TNF α and IL-6, which is increased by IL-1 β . 137-142”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [138]

    The Discussion (page not available in our copy) says IL-6 levels increase with COVID-19 disease severity, supporting the IL-6 portion. It does not address elevated TNFα or say that IL-1β increases IL-6. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The Tim-3/IL-10 pathway may be responsible for the inhibited T-cell responses reported during COVID-19 in some patients.

    “This pathway may be responsible for the inhibited T-cell responses that have been reported during COVID-19 in some patients. 138,139”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [138]

    The Discussion addresses complement activation and neutrophil responses in COVID-19, but does not connect Tim-3 or IL-10 to inhibited T-cell responses. Searches for the Tim-3/IL-10 pathway and T-cell inhibition found no passage in our copy addressing that proposed mechanism. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Metadata

Authors
Huber, S., Massri, M., Grasse, M., Fleischer, V., Kellnerová, S., Harpf, V., Knabl, L., Knabl, L., Heiner, T., Kummann, M., Neurauter, M., Rambach, G., Speth, C., & Würzner, R.
Affiliations
  • Innsbruck Medical University (AT)
  • Department of Anesthesia and Intensive Care Medicine, Hospital Reutte, 6600 Reutte, Austria
Corresponding author
Würzner, Reinhard
ORCID
Venue
Viruses
Publisher
MDPI AG
Published
2021-11-26
Volume
13
Issue
12
Pages
2376
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v13122376
PMC
PMC8707937
OpenAlex
W3216382377
Cited by
23
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 9 · 2022: 7
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • FWF Austrian Science Fund (W1253)
  • Horizon 2020 (860044)
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Keywords
COVID-19 pandemic, SARS-CoV-2, complement activation, NETosis, neutrophil extracellular traps, C5a, tracheal fluid, mechanical ventilation, systemic inflammation, coagulation, C-reactive protein, prognostic factors, clinical outcome prediction
MeSH terms
COVID-19, SARS-CoV-2, Aged, Aged, 80 and over, Complement Activation, Epithelial Cells, Female, Humans, Inflammation, Kinetics, Longitudinal Studies, Male, Prospective Studies, Thorax, Complement C5a, Cytokines, Viral Load

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