Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study

Bruni, Flavio; Charitos, Panteleimon; Lampart, Maurin; Moser, Stephan; Siegemund, Martin; Bingisser, Roland; Oßwald, Stefan; Bassetti, Stefano; Twerenbold, Raphael; Trendelenburg, Marten; Rentsch, Katharina; Osthoff, Michael

doi:10.3389/fimmu.2022.941742

Cited by 12 publications

(17 citation statements)

References 60 publications

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“…Amidst all, many protein changes in ECFCs+Crit cells were linked to CVDs, including cardiomyopathy (also seen in ECFCs+PCR cells), ventricular dysfunction, vaso-occlusion and thrombosis, ischemic stroke or even kidney thrombosis. In agreement with these results, functional assays reported that the levels of VCAM1 were up-regulated in response to all positive serums, as already seen in COVID-19 patients [73][74][75], while the angiogenic potential of ECFCs was impaired. Both situations are indicative of endothelial dysfunction associated with cardiovascular events [33,75].…”

Section: Discussionsupporting

confidence: 88%

Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients

Beltrán-Camacho¹,

Bhosale²,

Sánchez-Morillo³

et al. 2023

Int. J. Biol. Sci.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly affects the cardiovascular system, causing vascular damage and thromboembolic events in critical patients. Endothelial dysfunction represents one of the first steps in response to COVID-19 that might lead to cardiovascular complications and long-term sequelae. However, despite the enormous efforts in the last two years, the molecular mechanisms involved in such processes remain poorly understood. Herein, we analyzed the protein changes taking place in endothelial colony forming cells (ECFCs) after the incubation with the serum from individuals infected with COVID-19, whether asymptomatic or critical patients, by application of a label free-quantitative proteomics approach. Specifically, ECFCs from healthy individuals were incubated ex-vivo with the serum of either COVID-19 negative donors (PCR-/IgG-, n:8), COVID-19 asymptomatic donors at different infective stages (PCR+/ IgG-, n:8and PCR-/IgG+, n:8), or hospitalized critical COVID-19 patients (n:8), followed by proteomics analysis. In total, 590 proteins were differentially expressed in ECFCs in response to all infected serums. Predictive analysis highlighted several proteins like CAPN5, SURF4, LAMP2 or MT-ND1, as highly discriminating features between the groups compared. Protein changes correlated with viral infection, RNA metabolism or autophagy, among others. Remarkably, the angiogenic potential of ECFCs in response to the infected serums was impaired, and many of the protein alterations in response to the serum of critical patients were associated with cardiovascular-related pathologies.

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Section: Discussionsupporting

confidence: 88%

Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients

Beltrán-Camacho¹,

Bhosale²,

Sánchez-Morillo³

et al. 2023

Int. J. Biol. Sci.

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“…However, it is worth noting that three reports are currently contrasting with this trend. For instance, Bruni et al (29) stated that COVID-19 patients had insignificant levels of Gal-3 compared to controls. In line with this, Kusnierz-Cabala et al (34) reported no significant difference in serum Gal-3 levels in COVID-19 patients compared with healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…After removing duplicates, 524 records were screened by titles and abstracts. Following this step, 63 studies were evaluated by full texts, resulting in 18 final included studies (7,(19)(20)(21)(22)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). The PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) flow chart summarizing the selection process is available in Figure 1.…”

Section: Literature Search and Baseline Characteristics Of Included S...mentioning

confidence: 99%

Galectins can serve as biomarkers in COVID-19: A comprehensive systematic review and meta-analysis

et al. 2023

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BackgroundGalectins are an eleven-member class of lectins in humans that function as immune response mediators and aberrancies in their expression are commonly associated with immunological diseases. Several studies have focused on galectins as they may represent an important biomarker and a therapeutic target in the fight against COVID-19. This systematic review and meta-analysis examined the usefulness of clinical assessment of circulating galectin levels in patients with COVID-19.MethodsInternational databases including PubMed, Scopus, Web of Science, and Embase were systematically used as data sources for our analyses. The random-effect model was implemented to calculate the standardized mean difference (SMD) and a 95% confidence interval (CI).ResultsA total of 18 studies, comprising 2,765 individuals, were identified and used in our analyses. We found that Gal-3 is the most widely investigated galectin in COVID-19. Three studies reported significantly higher Gal-1 levels in COVID-19 patients. Meta-analysis revealed that patients with COVID-19 had statistically higher levels of Gal-3 compared with healthy controls (SMD 0.53, 95% CI 0.10 to 0.96, P=0.02). However, there was no significant difference between severe and non-severe cases (SMD 0.45, 95% CI -0.17 to 1.07, P=0.15). While one study supports lower levels of Gal-8 in COVID-19, Gal-9 was measured to be higher in patients and more severe cases.ConclusionOur study supports Gal-3 as a valuable non-invasive biomarker for the diagnosis and/or prognosis of COVID-19. Moreover, based on the evidence provided here, more studies are needed to confirm a similar diagnostic and prognostic role for Gal-1, -8, and -9.

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“…ICAM-1 and VCAM-1 are cell adhesion molecules that mediate leukocyte-endothelial cell interactions and are expressed on injured lung and kidney tissues in COVID-19 and other forms of acute illness (37)(38)(39)(40)(41). They have also been linked to mortality in these settings, but their relationship to AKI is inconsistent (12,(42)(43)(44). sPDL-1 is the soluble form of a checkpoint molecule whose role in respiratory illness is not well-established.…”

Section: Discussionmentioning

confidence: 99%

Biomarker Signatures of Severe Acute Kidney Injury in a Critically Ill Cohort of COVID-19 and Non-COVID-19 Acute Respiratory Illness

Sathe

Mostaghim

Barnes

et al. 2023

Critical Care Explorations

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IMPORTANCE: Kidney and lung injury are closely inter-related during acute respiratory illness, but the molecular risk factors that these organ injuries share are not well defined. OBJECTIVES: We identified plasma biomarkers associated with severe acute kidney injury (AKI) during acute respiratory illness, and compared them to biomarkers associated with severe acute respiratory failure (ARF). DESIGN, SETTINGS, AND PARTICIPANTS: Prospective observational cohort study enrolling March 2020 through May 2021, at three hospitals in a large academic health system. We analyzed 301 patients admitted to an ICU with acute respiratory illness. MAIN OUTCOMES AND MEASURES: Outcomes were ascertained between ICU admission and day 14, and included: 1) severe AKI, defined as doubling of serum creatinine or new dialysis and 2) severe ARF, which included new or persistent need for high-flow oxygen or mechanical ventilation. We measured biomarkers of immune response and endothelial function, pathways related to adverse kidney and lung outcomes, in plasma collected within 24 hours of ICU admission. Severe AKI occurred in 48 (16%), severe ARF occurred in 147 (49%), and 40 (13%) patients experienced both. Two-fold higher concentrations of soluble tumor necrosis factor receptor-1 (sTNFR-1) (adjusted relative risk [aRR], 1.56; 95% CI, 1.24–1.96) and soluble triggering receptor on myeloid cells-1 (sTREM-1) (aRR, 1.85; 95% CI, 1.42–2.41), biomarkers of innate immune activation, were associated with higher risk for severe AKI after adjustment for age, sex, COVID-19, and Acute Physiology and Chronic Health Evaluation-III. These biomarkers were not significantly associated with severe ARF. Soluble programmed cell death receptor-1 (sPDL-1), a checkpoint pathway molecule, as well as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1), molecules involved with endothelial-vascular leukocyte adhesion, were associated with both severe AKI and ARF. CONCLUSIONS AND RELEVANCE: sTNFR-1 and sTREM-1 were linked strongly to severe AKI during respiratory illness, while sPDL-1, sICAM-1 and sVCAM-1 were associated with both severe AKI and ARF. These biomarker signatures may shed light on pathophysiology of lung-kidney interactions, and inform precision medicine strategies for identifying patients at high risk for these organ injuries.

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Complement and endothelial cell activation in COVID-19 patients compared to controls with suspected SARS-CoV-2 infection: A prospective cohort study

Cited by 12 publications

References 60 publications

Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients

Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients

Galectins can serve as biomarkers in COVID-19: A comprehensive systematic review and meta-analysis

Biomarker Signatures of Severe Acute Kidney Injury in a Critically Ill Cohort of COVID-19 and Non-COVID-19 Acute Respiratory Illness

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