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. 2021 Jun 4;12(6):e00348.
doi: 10.14309/ctg.0000000000000348.

Low-Grade Endotoxemia and Thrombosis in COVID-19

Alessandra Oliva  1 , Vittoria Cammisotto  2 , Roberto Cangemi  3 , Domenico Ferro  4 , Maria Claudia Miele  1 , Massimiliano De Angelis  1 , Francesca Cancelli  1 , Pasquale Pignatelli  4   5 , Mario Venditti  1 , Francesco Pugliese  2 , Claudio Maria Mastroianni  1 , Francesco Violi  4   5
Affiliations

Low-Grade Endotoxemia and Thrombosis in COVID-19

Alessandra Oliva et al. Clin Transl Gastroenterol. .

Abstract

Introduction: Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications.

Methods: We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered.

Results: Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11-27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events.

Discussion: The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.

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Conflict of interest statement

Guarantor of the article: Francesco Violi, MD.

Specific author contributions: Alessandra Oliva, MD, and Vittoria Cammisotto, MSc, equally contributed. A.O.: study design and coordination. V.C.: laboratory analysis. R.C.: statistical analysis and draft elaboration. D.F.: patients' recruitment and follow-up. M.C.M., M.D.A., and F.C.: laboratory analysis. P.P.: data interpretation and draft elaboration. M.V., F.P., and C.M.M.: data interpretation and article elaboration. F.V.: study conception and coordination, data interpretation, and writing the manuscript.

Financial support: This research was funded by grant from PhD course: Fisiopatologia Ed Imaging Cardio-Toraco-Vascolare, Sapienza University of Rome.

Potential competing interests: None to report.

Figures

Figure 1.
Figure 1.
Scatter plot showing significant (2-tailed) Spearman positive correlation of zonulin in horizontal vs vertical directions of LPS concentration.
Figure 2.
Figure 2.
TIRAP phosphorylation (n = 21, a), MyD88 and TIRAP co-immunoprecipitation (n = 12, c) in patients with COVID-19 and HS. Data are expressed as mean values ± SDs and *P < 0.05. Representative western blot bands of TIRAP phosphorylation and immune complexes TIRAP/MyD88 (b and d). TIRAP, Toll/interleukin-1 receptor domain-containing adapter protein. A.U., arbitrary unit; HS, Healthy subjects; MyD88, Myeloid differentiation factor 88.
See this image and copyright information in PMC

Comment in

References

    1. Bilaloglu S, Aphinyanaphongs Y, Jones S, et al. . Thrombosis in hospitalized patients with COVID-19 in a New York City Health System. JAMA 2020;324:799–801. - PMC - PubMed
    1. Bikdeli B, Madhavan MV, Jimenez D, et al. . COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. J Am Coll Cardiol 2020;75:2950–73. - PMC - PubMed
    1. Cangemi R, Della Valle P, Calvieri C, et al. . Low-grade endotoxemia and clotting activation in the early phase of pneumonia. Respirology 2016;21:1465–71. - PubMed
    1. Cangemi R, Casciaro M, Rossi E, et al. . Platelet activation is associated with myocardial infarction in patients with pneumonia. J Am Coll Cardiol 2014;64:1917–25. - PubMed
    1. Carnevale R, Sciarretta S, Valenti V, et al. . Low-grade endotoxaemia enhances artery thrombus growth via Toll-like receptor 4: Implication for myocardial infarction. Eur Heart J 2020;41:3156–65. - PubMed

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