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.
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)
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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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.
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Conflict of interest statement: The authors declare no conflicts of interest regarding this article.
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