Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis

Andrianto, Andrianto; Al-Farabi, Makhyan Jibril; Nugraha, Ricardo Adrian; Marsudi, Bagas Adhimurda; Azmi, Yusuf

doi:10.1016/j.mvr.2021.104224

Cited by 48 publications

(35 citation statements)

References 45 publications

(45 reference statements)

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“…Meta-analysis showed that higher plasma levels of vWF antigen, tissue-type plasminogen activator, plasminogen activator inhibitor-1 antigen and soluble thrombomodulin were associated with poor outcome. 41 In the liver, strong vWF staining in sinusoidal endothelial cells was associated with increased platelet adhesion. 42 Consistent with these observations, we found increased immunostaining for vWF in the microthrombi.…”

Section: Discussionmentioning

confidence: 99%

Neurovascular injury with complement activation and inflammation in COVID-19

Lee

Perl

Steiner

et al. 2022

Brain

158

126

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The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to acute and long-term neurological manifestations remains obscure. We aimed to characterize the neuropathological changes in patients with coronavirus disease 2019 and determine the underlying pathophysiological mechanisms. In this autopsy study of the brain, we characterized the vascular pathology, the neuroinflammatory changes and cellular and humoral immune responses by immunohistochemistry. All patients died during the first wave of the pandemic from March to July 2020. All patients were adults who died after a short duration of the infection, some had died suddenly with minimal respiratory involvement. Infection with SARS-CoV-2 was confirmed on ante-mortem or post-mortem testing. Descriptive analysis of the pathological changes and quantitative analyses of the infiltrates and vascular changes were performed. All patients had multifocal vascular damage as determined by leakage of serum proteins into the brain parenchyma. This was accompanied by widespread endothelial cell activation. Platelet aggregates and microthrombi were found adherent to the endothelial cells along vascular lumina. Immune complexes with activation of the classical complement pathway were found on the endothelial cells and platelets. Perivascular infiltrates consisted of predominantly macrophages and some CD8 + T cells. Only rare CD4 + T cells and CD20 + B cells were present. Astrogliosis was also prominent in the perivascular regions. Microglial nodules were predominant in the hindbrain, which were associated with focal neuronal loss and neuronophagia. Antibody-mediated cytotoxicity directed against the endothelial cells is the most likely initiating event that leads to vascular leakage, platelet aggregation, neuroinflammation and neuronal injury. Therapeutic modalities directed against immune complexes should be considered.

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Section: Discussionmentioning

confidence: 99%

Neurovascular injury with complement activation and inflammation in COVID-19

Lee

Perl

Steiner

et al. 2022

Brain

158

126

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“…Several biomarkers other than cytokines have been found altered in COVID-19, and are associated with diagnosis, prognosis and outcomes ( 7 ). Some of these biomarkers can be easily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, like metabolomic and proteomic analysis, are still of purely investigational concern and difficult to translate into clinical practice, despite their prognostic potential ( 8 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

et al. 2022

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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP). Some of these biomarkers can be readily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, such as metabolomic and proteomic analysis, have not yet translated to clinical practice. This narrative review aims to identify laboratory biomarkers that have shown significant diagnostic and prognostic value for risk stratification in COVID-19 and discuss the possible clinical application of novel analytic strategies, like metabolomics and proteomics. Future research should focus on identifying a limited but essential number of laboratory biomarkers to easily predict prognosis and outcome in severe COVID-19.

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“…In July 2021, Andrianto et al [ 62 ] conducted a literature search for observational studies that analysed the relationship between ED biomarkers and clinical outcomes in COVID-19 patients. In a meta-analysis that included 1187 patients from 17 studies, VWF antigen, PAI-1, t-PA, sTM were predictors of worse outcome in COVID-19 patients.…”

Section: Discussionmentioning

confidence: 99%

Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial

et al. 2022

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Background The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. Methods The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. Discussion This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. Trial registration Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

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Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: A systematic review and meta-analysis

Cited by 48 publications

References 45 publications

Neurovascular injury with complement activation and inflammation in COVID-19

Neurovascular injury with complement activation and inflammation in COVID-19

Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19

Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial

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