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Molecular mechanisms of vasculopathy and coagulopathy in COVID-19

  • Suzan Al-Gburi ORCID logo EMAIL logo , Stefan Beissert and Claudia Günther EMAIL logo
Published/Copyright: October 19, 2021
Biological Chemistry
From the journal Biological Chemistry Volume 402 Issue 12

Abstract

COVID-19 primarily affects the respiratory system and may lead to severe systemic complications, such as acute respiratory distress syndrome (ARDS), multiple organ failure, cytokine storm, and thromboembolic events. Depending on the immune status of the affected individual early disease control can be reached by a robust type-I-interferon (type-I-IFN) response restricting viral replication. If type-I-IFN upregulation is impaired, patients develop severe COVID-19 that involves profound alveolitis, endothelitis, complement activation, recruitment of immune cells, as well as immunothrombosis. In patients with proper initial disease control there can be a second flare of type-I-IFN release leading to post-COVID manifestation such as chilblain-like lesions that are characterized by thrombosis of small vessels in addition to an inflammatory infiltrate resembling lupus erythematosus (LE). Mechanistically, SARS-CoV-2 invades pneumocytes and endothelial cells by acting on angiotensin-II-converting enzyme 2 (ACE2). It is hypothesized, that viral uptake might downregulate ACE2 bioavailability and enhance angiotensin-II-derived pro-inflammatory and pro-thrombotic state. Since ACE2 is encoded on the X chromosome these conditions might also be influenced by gender-specific regulation. Taken together, SARS-CoV-2 infection affects the vascular compartment leading to variable thrombogenic or inflammatory response depending on the individual immune response status.

Keywords: angiotensin-II-converting-enzyme-2 (ACE2); coagulopathy; endothelitis; SARS-CoV-2; sex differences; vasculopathy
Corresponding authors: Suzan Al-Gburi and Claudia Günther, University Hospital Carl Gustav Carus, Technical University of Dresden, Fetscherstr. 74, D-01307 Dresden, Germany, E-mail: (S. Al-Gburi), (C. Günther)

This article is a contribution to the issue highlighting the 25th Anniversary of the Interdisciplinary Centre for Clinical Research (IZKF) Münster.

Funding source: Deutsche Forschungsgemeinschaft (German Research Foundation)

Award Identifier / Grant number: TRR237 369799452/404458960

Funding source: Medical Faculty Carl Gustav Carus (Technical University Dresden)

Award Identifier / Grant number: MeDDrive Programme (MeDDrive Start Project 2021/2022)

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation), grant TRR237 369799452/404458960 to CG; by the MeDDrive Programme (MeDDrive Start Project 2021/2022 grant to SA) of the Medical Faculty Carl Gustav Carus (Technical University Dresden), and by the Dresden Else Kröner Research College “Phosphoproteom-Dynamics” (membership of SA) of the Medical Faculty Carl Gustav Carus (Technical University Dresden), University Hospital Carl Gustav Carus Dresden.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2021-04-30
Accepted: 2021-10-06
Published Online: 2021-10-19
Published in Print: 2021-11-25

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Molecular Determinants of Health and Disease - 25th Anniversary of the InterdisciplinaryCenter Clinical Research Münster
  3. Molecular determinants of health and disease
  4. Role of the gut microbiota in airway immunity and host defense against respiratory infections
  5. Dynamic phospho-modification of viral proteins as a crucial regulatory layer of influenza A virus replication and innate immune responses
  6. Molecular mechanisms of vasculopathy and coagulopathy in COVID-19
  7. Astrocytic potassium and calcium channels as integrators of the inflammatory and ischemic CNS microenvironment
  8. Epitranscriptomic modifications in acute myeloid leukemia: m6A and 2′-O-methylation as targets for novel therapeutic strategies
  9. Molecular determinants of therapy response of venetoclax-based combinations in acute myeloid leukemia
  10. Pseudomonas aeruginosa and Staphylococcus aureus virulence factors as biomarkers of infection
  11. Controllers of cutaneous regulatory T cells: ultraviolet radiation and the skin microbiome
  12. The paracaspase MALT1 in psoriasis
  13. The cAMP responsive element modulator (CREM) is a regulator of CD4+ T cell function
  14. Quantifying salt sensitivity
  15. Life sciences and mass spectrometry: some personal reflections
https://doi.org/10.1515/hsz-2021-0245
Keywords for this article
angiotensin-II-converting-enzyme-2 (ACE2); coagulopathy; endothelitis; SARS-CoV-2; sex differences; vasculopathy

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Molecular Determinants of Health and Disease - 25th Anniversary of the InterdisciplinaryCenter Clinical Research Münster
  3. Molecular determinants of health and disease
  4. Role of the gut microbiota in airway immunity and host defense against respiratory infections
  5. Dynamic phospho-modification of viral proteins as a crucial regulatory layer of influenza A virus replication and innate immune responses
  6. Molecular mechanisms of vasculopathy and coagulopathy in COVID-19
  7. Astrocytic potassium and calcium channels as integrators of the inflammatory and ischemic CNS microenvironment
  8. Epitranscriptomic modifications in acute myeloid leukemia: m6A and 2′-O-methylation as targets for novel therapeutic strategies
  9. Molecular determinants of therapy response of venetoclax-based combinations in acute myeloid leukemia
  10. Pseudomonas aeruginosa and Staphylococcus aureus virulence factors as biomarkers of infection
  11. Controllers of cutaneous regulatory T cells: ultraviolet radiation and the skin microbiome
  12. The paracaspase MALT1 in psoriasis
  13. The cAMP responsive element modulator (CREM) is a regulator of CD4+ T cell function
  14. Quantifying salt sensitivity
  15. Life sciences and mass spectrometry: some personal reflections
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