Immune-Mediated Glycocalyx Remodeling in Hospitalized COVID-19 Patients

Springer Science and Business Media LLC - Tập 37 Số 2 - Trang 307-313 - 2023
Sascha N. Goonewardena1, Olga Grushko1, Joanna Wells1, Lauren Herty2, Robert S. Rosenson3, Jacob M. Haus4, Scott L. Hummel2
1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
2Ann Arbor Veterans Affairs Health System, Ann Arbor, MI, USA
3Metabolism and Lipids Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA
4School of Kinesiology, University of Michigan, Ann Arbor, MI, USA

Tóm tắt

Abstract Purpose Vascular and immune dysfunction are hallmarks of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections and coronavirus disease 2019 (COVID-19). Although our understanding of the pathogenesis of COVID-19 has rapidly evolved, much of the focus has been on the immune mechanisms underlying COVID-19. In addition to immune dysfunction, vascular injury is also associated with COVID-19 and is a major driver of clinical deterioration in SARS-CoV-2 infections. The glycocalyx (GAC), a sugar-based shell that surrounds all mammalian cells, is an important regulator of vascular and immune responses. In sepsis, vascular dysfunction contributes to acute respiratory distress syndrome (ARDS) by altering vessel integrity, promoting thrombosis, and accelerating inflammation, all of which are also present in COVID-19. Observational studies in sepsis have found an association between levels of circulating GAC degradation products with both organ dysfunction and mortality. Although vascular dysfunction is a hallmark of COVID-19, it remains unclear whether GAC disruption occurs in COVID-19 and if GAC disruption contributes to the clinical progression of COVID-19. Methods In this prospective cohort study, we measured the GAC components syndecan-1 (SDC1) and hyaluronan (Hyal) along with inflammatory cytokines in 12 hospitalized COVID-19 patients and 8 healthy controls (HC). Results In agreement with other studies, we found that inflammatory cytokines are elevated in hospitalized COVID-19 patients compared with HC [median (IQR), all units picograms per milliliter: IL-6 4.65 (3.32–9.16) vs 0.69 (0.55–0.89), p < 0.001; TNFα 4.49 (1.87–8.03) vs 0.04 (0.04–0.84), p < 0.001]. Additionally, we found that the GAC components SDC1 and Hyal are also elevated in COVID-19 patients [median (IQR), all units picograms per milliliter: SDC1: 247.37 (101.43–458.26) vs 84.8 (52.88–123.59), p = 0.036; Hyal: 26.41 (16.4–35.1) vs 3.01 (1.66–4.61), p < 0.001]. Conclusion We propose that GAC markers offer insights into the pathobiology of COVID-19, potentially guide therapeutic approaches, and could aid in early risk stratification that is particularly beneficial in phasic diseases such as COVID-19.

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Springer Science and Business Media LLC

Tập 37 Số 2

307-313

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