Endothelial Damage, Neutrophil Extracellular Traps and Platelet Activation in COVID-19 vs. Community-Acquired Pneumonia: A Case-Control Study

Paula González-Jiménez; Raúl Méndez; Ana Latorre; Noé Mengot; Mónica Piqueras; Soledad Reyes; Antonio Moscardó; Ricardo Alonso; Isabel Amara-Elori; Rosario Menéndez

doi:10.3390/ijms241713194

Endothelial Damage, Neutrophil Extracellular Traps and Platelet Activation in COVID-19 vs. Community-Acquired Pneumonia: A Case-Control Study

Int J Mol Sci. 2023 Aug 25;24(17):13194. doi: 10.3390/ijms241713194.

Authors

Paula González-Jiménez^{1

2

3}, Raúl Méndez^{1

2

3

4}, Ana Latorre², Noé Mengot¹, Mónica Piqueras^{3

5}, Soledad Reyes^{1

2}, Antonio Moscardó⁶, Ricardo Alonso⁵, Isabel Amara-Elori^{1

2

3}, Rosario Menéndez^{1

2

3

4}

Affiliations

¹ Pneumology Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
² Respiratory Infections, Health Research Institute La Fe (IISLAFE), 46026 Valencia, Spain.
³ Medicine Department, University of Valencia, 46010 Valencia, Spain.
⁴ Center for Biomedical Research Network in Respiratory Diseases (CIBERES), 28029 Madrid, Spain.
⁵ Laboratory Department, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.
⁶ Hemostasis and Thrombosis Unit, La Fe University and Polytechnic Hospital, 46026 Valencia, Spain.

Abstract

COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers related to endothelial damage and immunothrombosis in COVID-19 in comparison to community-acquired pneumonia (CAP) through a case-control study of 358 patients with pneumonia (179 hospitalized with COVID-19 vs. 179 matched hospitalized with CAP). Endothelial damage markers (endothelin and proadrenomedullin), neutrophil extracellular traps (NETs) (citrullinated-3 histone, cell-free DNA), and platelet activation (soluble P-selectin) were measured. In-hospital and 1-year follow-up outcomes were evaluated. Endothelial damage, platelet activation, and NET biomarkers are significantly higher in CAP compared to COVID-19. In-hospital mortality in COVID-19 was higher compared to CAP whereas 1-year mortality and cardiovascular complications were higher in CAP. In the univariate analysis (OR 95% CIs), proADM and endothelin were associated with in-hospital mortality (proADM: CAP 3.210 [1.698-6.070], COVID-19 8.977 [3.413-23.609]; endothelin: CAP 1.014 [1.006-1.022], COVID-19 1.024 [1.014-1.034]), in-hospital CVE (proADM: CAP 1.623 [1.080-2.439], COVID-19 2.146 [1.186-3.882]; endothelin: CAP 1.005 [1.000-1.010], COVID-19 1.010 [1.003-1.018]), and 1-year mortality (proADM: CAP 2.590 [1.644-4.080], COVID-19 13.562 [4.872-37.751]; endothelin: CAP 1.008 [1.003-1.013], COVID-19 1.026 [1.016-1.037]). In conclusion, COVID-19 and CAP showed different expressions of endothelial damage and NETs. ProADM and endothelin are associated with short- and long-term mortality.

Keywords: CAP; COVID-19; case–control; endothelial damage; neutrophil extracellular traps; platelet activation.

MeSH terms

COVID-19*
Case-Control Studies
Community-Acquired Infections*
Extracellular Traps*
Humans
Platelet Activation
Pneumonia*

Grants and funding

This study was supported by Instituto de Salud Carlos III (ISCIII) through Project [PI17/01421] and Project [COV20/00385] (co-funded by the European Regional Development Fund/European Social Fund, “Investing in your future”); Sociedad Española de Neumología y Cirugía Torácica (SEPAR): 914/2019, 1078/2020; Sociedad Valenciana de Neumología (SVN): 2018, 2019, and 2021; and a non-conditional grant from Menarini S.A. (2020-282-01). Paula González-Jiménez is the recipient of a post-resident research grant supported by the Health Research Institute La Fe (2019-053-1). Raúl Méndez is the recipient of a Juan Rodés grant, supported by the Instituto de Salud Carlos III (ISCIII JR21/00051). The funding source did not have any role in the design, data obtention, analyses, interpretation of results, or drafting of the manuscript. All authors had full access to all of the data in the study and had the final responsibility of making the decision to submit the manuscript for publication.