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1.
J Thromb Haemost ; 20(5): 1206-1212, 2022 05.
Article in English | MEDLINE | ID: covidwho-1745875

ABSTRACT

BACKGROUND: Pulmonary embolism (PE) occurs in one-third of critically-ill COVID-19 patients. Although prior studies identified several pathways contributing to thrombogenicity, it is unknown whether this is COVID-19-specific or also occurs in ARDS patients with another infection. OBJECTIVE: To compare pathway activity among patients having COVID-19 with PE (C19PE+), COVID-19 without PE (C19PE-), and influenza-associated ARDS (IAA) using a targeted proteomics approach. METHODS: We exploited an existing biorepository containing daily plasma samples to carefully match C19PE+ cases to C19PE- and IAA controls on mechanical ventilation duration, PEEP, FiO2, and cardiovascular-SOFA (n = 15 per group). Biomarkers representing various thrombosis pathways were measured using proximity extension- and ELISA-assays. Summed z-scores of individual biomarkers were used to represent total pathway activity. RESULTS: We observed no relevant between-group differences among 22 biomarkers associated with activation of endothelium, platelets, complement, coagulation, fibrinolysis or inflammation, except sIL-1RT2 and sST2, which were lower in C19PE- than IAA (log2-Foldchange -0.67, p = .022 and -1.78, p = .022, respectively). However, total pathway analysis indicated increased activation of endothelium (z-score 0.2 [-0.3-1.03] vs. 0.98 [-2.5--0.3], p = .027), platelets (1.0 [-1.3-3.0] vs. -3.3 [-4.1--0.6], p = .023) and coagulation (0.8 [-0.5-2.0] vs. -1.0 [-1.6-1.0], p = .023) in COVID-19 patients (C19PE+/C19PE- groups combined) compared to IAA. CONCLUSION: We observed only minor differences between matched C19PE+, C19PE-, and IAA patients, which suggests individual biomarkers mostly reflect disease severity. However, analysis of total pathway activity suggested upregulation of some distinct processes in COVID-19 could be etiologically related to increased PE-risk.


Subject(s)
COVID-19 , Influenza, Human , Pulmonary Embolism , Respiratory Distress Syndrome , Thrombosis , Biomarkers , COVID-19/complications , Humans , Influenza, Human/complications , Influenza, Human/diagnosis , Proteomics , Pulmonary Embolism/diagnosis , SARS-CoV-2
2.
Cardiovasc Res ; 117(8): 1814-1822, 2021 07 07.
Article in English | MEDLINE | ID: covidwho-1301347

ABSTRACT

2020 has been an extraordinary year. The emergence of COVID-19 has driven urgent research in pulmonary and cardiovascular science and other fields. It has also shaped the way that we work with many experimental laboratories shutting down for several months, while bioinformatics approaches and other large data projects have gained prominence. Despite these setbacks, vascular biology research is stronger than ever. On behalf of the European Society of Cardiology Council for Basic Cardiovascular Science (ESC CBCS), here we review some of the vascular biology research highlights for 2020. This review is not exhaustive and there are many outstanding vascular biology publications that we were unable to cite due to page limits. Notwithstanding this, we have provided a snapshot of vascular biology research excellence in 2020 and identify topics that are in the ascendency and likely to gain prominence in coming years.


Subject(s)
COVID-19/diagnosis , Extracellular Traps/physiology , Neutrophils/cytology , Smartphone , Computational Biology , Humans , SARS-CoV-2/pathogenicity
3.
Cardiovasc Res ; 117(10): 2161-2174, 2021 08 29.
Article in English | MEDLINE | ID: covidwho-1266111

ABSTRACT

We review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches, such as a glycocalyx mimetic, were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to-cell communication, in particular, the relevance of extracellular vesicles, such as exosomes, which transport proteins, lipids, non-coding RNAs, and mRNAs and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding RNA-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular RNA circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart.


Subject(s)
Biomedical Research , Cardiology , Cell Proliferation , Heart Failure/pathology , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/pathology , Myocytes, Cardiac/pathology , Regeneration , Animals , COVID-19/pathology , COVID-19/virology , Cell Communication , Cellular Microenvironment , Exosomes/metabolism , Exosomes/pathology , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , Mitochondria, Heart/metabolism , Mitochondria, Heart/pathology , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/virology , Phenotype , RNA, Untranslated/metabolism , SARS-CoV-2/pathogenicity
4.
J Infect Dis ; 223(8): 1322-1333, 2021 04 23.
Article in English | MEDLINE | ID: covidwho-1057852

ABSTRACT

The clinical spectrum of COVID-19 varies and the differences in host response characterizing this variation have not been fully elucidated. COVID-19 disease severity correlates with an excessive proinflammatory immune response and profound lymphopenia. Inflammatory responses according to disease severity were explored by plasma cytokine measurements and proteomics analysis in 147 COVID-19 patients. Furthermore, peripheral blood mononuclear cell cytokine production assays and whole blood flow cytometry were performed. Results confirm a hyperinflammatory innate immune state, while highlighting hepatocyte growth factor and stem cell factor as potential biomarkers for disease severity. Clustering analysis revealed no specific inflammatory endotypes in COVID-19 patients. Functional assays revealed abrogated adaptive cytokine production (interferon-γ, interleukin-17, and interleukin-22) and prominent T-cell exhaustion in critically ill patients, whereas innate immune responses were intact or hyperresponsive. Collectively, this extensive analysis provides a comprehensive insight into the pathobiology of severe to critical COVID-19 and highlights potential biomarkers of disease severity.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , Immunity, Innate/immunology , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Cytokines/immunology , Female , Humans , Inflammation/blood , Inflammation/immunology , Inflammation/virology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/virology , Lymphopenia/blood , Lymphopenia/immunology , Lymphopenia/virology , Male , Middle Aged , SARS-CoV-2/immunology , Severity of Illness Index
5.
Cardiovasc Res ; 116(14): 2177-2184, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-693970

ABSTRACT

The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world. Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system. In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm. This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19. There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19. Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address. We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients. A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications.


Subject(s)
COVID-19/virology , Cardiovascular Diseases/virology , Endothelium, Vascular/virology , SARS-CoV-2/pathogenicity , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/physiopathology , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Cytokines/metabolism , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Host-Pathogen Interactions , Humans , Inflammation Mediators/metabolism , Prognosis , Risk Assessment , Risk Factors , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Virus Internalization
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