Frontiers in immunology
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Frontiers in immunology · Jan 2020
Non-invasive Assessment of Mitochondrial Oxygen Metabolism in the Critically Ill Patient Using the Protoporphyrin IX-Triplet State Lifetime Technique-A Feasibility Study.
The imbalance of oxygen delivery and oxygen consumption resulting in insufficient tissue oxygenation is pathognomonic for all forms of shock. Mitochondrial function plays an important role in the cellular oxygen metabolism and has been shown to impact a variety of diseases in the intensive care setting, specifically sepsis. Clinical assessment of tissue oxygenation and mitochondrial function remains elusive. ⋯ Notably, higher levels of hydration were associated with lower mitochondrial oxygen tension. We conclude that COMET measurements are viable in patients with sepsis. To validate the clinical and diagnostic relevance of the PpIX-TSLT using the COMET in the intensive care setting, future studies in critically ill patients and healthy controls are needed.
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Frontiers in immunology · Jan 2020
Observational StudyComplement Activation Is Associated With Mortality in Patients With Necrotizing Soft-Tissue Infections-A Prospective Observational Study.
Aim: We assessed whether different complement factors and complement activation products were associated with poor outcome in patients with necrotizing soft-tissue infection (NSTI). Methods: We conducted a prospective, observational study in an intensive care unit where treatment of NSTI is centralized at a national level. In 135 NSTI patients and 65 control patients, admission levels of MASP-1, MASP-2, MASP-3, C4, C3, complement activation products C4c, C3bc, and terminal complement complex (TCC) were assessed. ⋯ Conclusion: In adjusted analyses, high admission levels of the C4c/C4 ratio, C3bc, and the C3bc/C3 ratio were significantly associated with a higher risk of death after 90 days while high admission levels of MASP-1 and C4 were associated with lower risk. In this cohort, these variables are better predictors of mortality in NSTI than C-reactive protein and Procalcitonin. C4's ability to predict mortality was comparable to the well-established scoring systems SAPS score II and SOFA on day 1.
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Frontiers in immunology · Jan 2020
Combating COVID-19: MVA Vector Vaccines Applied to the Respiratory Tract as Promising Approach Toward Protective Immunity in the Lung.
The lung is the vital target organ of coronavirus disease 2019 (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the majority of patients the most active virus replication seems to be found in the upper respiratory tract, severe cases however suffer from SARS-like disease associated with virus replication in lung tissues. ⋯ However, past experience from experimental animals, livestock, and humans showed that induction of immunity in the lung is limited following application of vaccines at peripheral sides such as skin or muscles. Based on several considerations we therefore propose here to consider the application of a Modified Vaccinia virus Ankara (MVA)-based vaccine to mucosal surfaces of the respiratory tract as a favorable approach to combat COVID-19.
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Frontiers in immunology · Jan 2020
Can Beta-2-Adrenergic Pathway Be a New Target to Combat SARS-CoV-2 Hyperinflammatory Syndrome?-Lessons Learned From Cancer.
SARS-CoV-2 infection is a new threat to global public health in the 21st century (2020), which has now rapidly spread around the globe causing severe pneumonia often linked to Acute Respiratory Distress Syndrome (ARDS) and hyperinflammatory syndrome. SARS-CoV-2 is highly contagious through saliva droplets. The structural analysis suggests that the virus enters human cells through the ligation of the spike protein to angiotensin-converting enzyme 2 (ACE2). ⋯ Blocking (B2AR) has been proven, also in clinical settings, to reduce Th-17 response and negatively modulate inflammatory cytokines including IL-6 while increasing IFNγ. Non-selective beta-blockers are currently used to treat several diseases and have been proven to reduce stress-induced inflammation and reduce anxiety. For these reasons, we speculate that targeting B2AR in the early phase of Covid-19 might be beneficial to prevent hyperinflammation.
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Frontiers in immunology · Jan 2020
Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key?
To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein-Kinin (KKS), the Coagulation/Fibrinolysis and the Renin-Angiotensin (RAS) Systems. ⋯ Angiotensin-Converting-Enzyme (ACE) 2 displays lung protective effects: it inactivates DABK and converts Angiotensin II (Ang II) into Angiotensin-(1-7) and Angiotensin I into Angiotensin-(1-9). SARS-CoV-2 binds to ACE2 for cell entry, downregulating it: an impaired DABK inactivation could lead to an enhanced activity of B1-receptors, and the accumulation of Ang II, through a negative feedback loop, may result in decreased ACE activity, with consequent increase of BK. Therapies targeting the CS, the KKS and action of BK could be effective for the treatment of COVID-19.