Article ; Online: Elevated Cytokine Levels in Plasma of Patients with SARS-CoV-2 Do Not Contribute to Pulmonary Microvascular Endothelial Permeability.
2022 Volume 10, Issue 1, Page(s) e0167121
Abstract: The vascular endothelial injury occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but the mechanisms are poorly understood. We sought to determine the frequency and type of cytokine elevations and their relationship to ... ...
| Abstract | The vascular endothelial injury occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, but the mechanisms are poorly understood. We sought to determine the frequency and type of cytokine elevations and their relationship to endothelial injury induced by plasma from patients with SARS-CoV-2 versus controls. Plasma from eight consecutively enrolled patients hospitalized with acute SARS-CoV-2 infection was compared to controls. Endothelial cell (EC) barrier integrity was evaluated using ECIS (electric cell-substrate impedance sensing) on human lung microvascular EC. Plasma from all SARS-CoV-2 but none from controls decreased transendothelial resistance to a greater degree than that produced by tumor necrosis factor-alpha (TNF-α), the positive control for the assay. Thrombin, angiopoietin 2 (Ang2), and vascular endothelial growth factor (VEGF), complement factor C3a and C5a, and spike protein increased endothelial permeability, but to a lesser extent and a shorter duration when compared to SARS-CoV-2 plasma. Analysis of Ang2, VEGF, and 15 cytokines measured in plasma revealed striking patient-to-patient variability within the SARS-CoV-2 patients. Pretreatment with thrombin inhibitors, single, or combinations of neutralizing antibodies against cytokines, Ca3 and C5a receptor antagonists, or with ACE2 antibody failed to lessen the SARS-CoV-2 plasma-induced EC permeability. The EC barrier destructive effects of plasma from patients with SARS-CoV-2 were susceptible to heat inactivation. Plasma from patients hospitalized with acute SARS-CoV-2 infection uniformly disrupts lung microvascular integrity. No predicted single, or set of, cytokine(s) accounted for the enhanced vascular permeability, although the factor(s) were heat-labile. A still unidentified but potent circulating factor(s) appears to cause the EC disruption in SARS-CoV-2 infected patients. |
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| MeSH term(s) | Adult ; Aged ; COVID-19/blood ; COVID-19/physiopathology ; COVID-19/virology ; Capillary Permeability ; Cytokines/blood ; Endothelial Cells/virology ; Female ; Humans ; Lung/blood supply ; Lung/virology ; Male ; Middle Aged ; SARS-CoV-2/genetics ; SARS-CoV-2/physiology ; Tumor Necrosis Factor-alpha/blood ; Vascular Endothelial Growth Factor A ; Young Adult |
| Chemical Substances | Cytokines ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A |
| Language | English |
| Publishing date | 2022-02-16 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2807133-5 |
| ISSN | 2165-0497 ; 2165-0497 |
| ISSN (online) | 2165-0497 |
| ISSN | 2165-0497 |
| DOI | 10.1128/spectrum.01671-21 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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