Erythrocytes Identify Complement Activation in Patients with COVID-19

2021 ◽  
Author(s):  
LK Metthew Lam ◽  
John Patrick Reilly ◽  
Ann H Rux ◽  
Sophia Murphy ◽  
Leticia Kuri-Cervantes ◽  
...  
Keyword(s):  
Organ Failure ◽  
Complement Activation ◽  
Clinical Evidence ◽  
Diagnostic Value ◽  
Organ Injury ◽  
Complement Receptors ◽  
Thromboembolic Complications ◽  
Complement Dysregulation ◽  
System Organ

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multi-system organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and pre-clinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in COVID-19 patients using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.

The Pathophysiology of Multi-System Organ Failure in the Trauma Patient

1990 ◽  
Vol 1 (3) ◽  
pp. 465-476 ◽  
Author(s):  
Ann N. Hotter
Keyword(s):  
Organ Failure ◽  
Care Setting ◽  
Inflammatory Factors ◽  
System Failure ◽  
Organ Systems ◽  
Organ System Failure ◽  
Trauma Mortality ◽  
Physiologic Effect ◽  
System Organ

Multiple trauma mortality in the critical care setting most often occurs as a result of multi-system organ failure (MSOF). Mortality rates increase exponentially as successive organ systems fail. Although the role of shock in determining patient outcome has been extensively investigated, inflammatory factors and sepsis are becoming increasingly implicated in the development of MSOF. The physiologic effect of these factors on individual organ systems is explained. Signs, symptoms, and key criteria for determining organ system failure also are presented to assist the nurse in recognition and prevention

scholarly journals Η σημασία του μηχανικού καθαρισμού του πεπτικού σωλήνος για την πρόληψη των μετεγχειρητικών λοιμώξεων στισ μείζονες ενδοκοιλιακές επεμβάσεις εκτός παχέος εντέρου

2000 ◽  
Author(s):  
Γεώργιος Κούκης
Keyword(s):  
Gastrointestinal Tract ◽  
Organ Failure ◽  
Bacterial Translocation ◽  
Immunosuppressive Agents ◽  
Intestinal Bacteria ◽  
Multiple Organ ◽  
Burn Care ◽  
Multiple System Organ ◽  
System Organ

Η μικροβιακή διαμετάθεση αποτελεί πιθανώς την αιτία της λοίμωξης από εντερικής προέλευσης μικροοργανισμούς .οι Danner και συν(1988) βρήκαν μικροβιαιμία από εντερικής προέλευσης μικροοργανισμούς στο 54% των ασθενών μιας ΜΕΘ με τοξιναιμία και στο 24% χωρίς τοξιναιμία. Οι Fiddian-Green και Gnantz (1987) ενοχοποιούν την διαμετάθεση ως αιτία των λοιμώξεων από εντερικής προέλευσης μικροοργανισμούς στο 54%σε ασθενείς που υφίστανται χειρουργικές επεμβάσεις επί της κοιλιακής αορτής δεδομένου ότι η επίπτωση των λοιμώξεων αυτών αυξάνεται αλματωδώς όσο αυξάνεται η οξέωση του παχέος εντέρου ενδοβλεννογονίως. Η ενδοβλεννογόνιος οξέωση προηγείται κατά μερικές ημέρες των ενδοσκοπικών ευρημάτων της ισχαιμικής κολίτιδας η οποία έπεται κατά δυο ως δεκατέσσερις ημέρες της εμφάνισης μικροοργανισμών στο αίμα. Επίσης οι Fabian και συν(1988) απομόνωσαν εντερικής προέλευσης μικροοργανισμούς στο αίμα ασθενών της Μ.Ε.Θ, στην συντριπτική πλειοψηφία των οποίων συνοδευόταν από αύξηση των επίπεδων του γαλακτικού οξέος, που ερμηνεύτηκε ως ένδειξη ιστικής ισχαιμίας. (Antonsson και Fiddian-Green 1991).Από την παρούσα εργασία προκύπτουν αρκετά συμπεράσματα με πρώτο και κύριο την στατιστική απόδειξη της μειώσεως των λοιμώξεων όταν έχουμε μείωση του μικροβιακού φορτίου του εντέρου. Την μείωση αυτή την επιτύχαμε με τον μηχανικό καθαρισμό του εντέρου, μια διαδικασία εύκολη, χαμηλού κόστους και άριστα ανεκτή από τον ασθενή.ΕΝΔΕΙΚΤΙΚΗ ΒΙΒΛΙΟΓΡΑΦΙΑ1. Antonsson J.B. and Fiddian Green R.G. The role of the gut in shock and multiple system organ failure. Eur. J.Syrg. 157: 3, 19912. Berg R.D. Bacterial translocation from the gastrointestinal tract of mice receiving immunosuppressive agents. Current Microbiol. 8: 285, 1983 (ως Berg R.D. 1983).3. Cuevas P and Fine J. Route of absorption from the intestine in the non septic shock. J. Reticuloedothel. Soc 11: 535, 1972 (ως Cuevas και Fine 1972-β).4. Deitch E.A. Bacterial translocation from the gut. A mechanism of infection. J Burn Care Rehabit. 8- 475, 1987 (ως Deitch E.A 1987).5. Fiddian-Green R.G. Splachnic ischemia and multiple organ failure in the critically ill. Ann. Coll. Surg. Engl. 70: 128, 1988 (ως Fiddian Green R.G. 1988).6. Gans H. and Matsumoto K. The escape of endotoxine from the intestine S.G.O. 139:395, 1974.7. Haglund U, Abe T, Cren C, Braide L and Lundgreen O. The intestinal mucosal lesions in shock. Eur. Surg. Res. 8: 435,1976 (ως Hanglud και συν. 1976).8. Levin J.Tomasulo P.A. and Oser R.S. Detection of endotoxine in human blood and demonstration of an inhibitor. J. Lab. Clin. Med. 75: 903, 1070.9. Owens W.E. and Berg R.D. Bacterial translocation coli from the gastrointestinal tract of athymic (nu/nu) mice. Infect. Immun. 27: 461, 1980.10. Wells C.L, Maddaus M.A, Hechoreck R.P, Simmons R.I. Role of macrophage in tranlocation of intestinal bacteria. Arch. Surg

scholarly journals Complement in structure and immune homeostasis in placenta

2021 ◽  
Author(s):  
Sanshan Jin ◽  
Canrong Wu ◽  
Yingchun Zhang
Keyword(s):  
Immune System ◽  
Complement Activation ◽  
Individual Case ◽  
Innate Immune ◽  
Complement Protein ◽  
Complement Dysregulation ◽  
Pathological Pregnancy ◽  
Structural Homeostasis ◽  
Fetal Antigens

Aberrant complement activation can induce “thrombo-inflammation” attacks to host tissue. Beside kidney and blood vessel, the placenta is also susceptible to these attacks. Complement dysregulation is recently classified as one of the new mechanisms leading to pregnancy disorders. Studies have indicated that dampening complement activation can ameliorate pregnancy outcomes. During pregnancy, the mother’s immune system is finely domesticated to accept the semi-allogeneic fetal antigens. As an important part of the innate immune system, some interesting changes have also taken place in complement system during pregnancy. The complement proteins are highly expressed in placenta, and their split products are increased. They are tuned in maintain placental immunity and structural homeostasis. An abundance of evidence shew that complement protein deficiency lead to autoimmunity disease and pathological pregnancy marked by excessive inflammation. Although complement suppressing strategies have been proven effective in treating some pathological pregnancy in individual case studies. we should take the dual role of the complement into consideration that fully and completely inhibit of complement may not be a wise choice.

scholarly journals Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis

Blood ◽  
2010 ◽  
Vol 116 (6) ◽  
pp. 1002-1010 ◽  
Author(s):  
Robert Silasi-Mansat ◽  
Hua Zhu ◽  
Narcis I. Popescu ◽  
Glenn Peer ◽  
Georgia Sfyroera ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Severe Sepsis ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Complement Activation ◽  
Degradation Products ◽  
Multiple Organ ◽  
Organ Injury ◽  
Organ Protection ◽  
Baboon Model

AbstractSevere sepsis leads to massive activation of coagulation and complement cascades that could contribute to multiple organ failure and death. To investigate the role of the complement and its crosstalk with the hemostatic system in the pathophysiology and therapeutics of sepsis, we have used a potent inhibitor (compstatin) administered early or late after Escherichia coli challenge in a baboon model of sepsis-induced multiple organ failure. Compstatin infusion inhibited sepsis-induced blood and tissue biomarkers of complement activation, reduced leucopenia and thrombocytopenia, and lowered the accumulation of macrophages and platelets in organs. Compstatin decreased the coagulopathic response by down-regulating tissue factor and PAI-1, diminished global blood coagulation markers (fibrinogen, fibrin-degradation products, APTT), and preserved the endothelial anticoagulant properties. Compstatin treatment also improved cardiac function and the biochemical markers of kidney and liver damage. Histologic analysis of vital organs collected from animals euthanized after 24 hours showed decreased microvascular thrombosis, improved vascular barrier function, and less leukocyte infiltration and cell death, all consistent with attenuated organ injury. We conclude that complement-coagulation interplay contributes to the progression of severe sepsis and blocking the harmful effects of complement activation products, especially during the organ failure stage of severe sepsis is a potentially important therapeutic strategy.

Melatonin and Neonatal Sepsis: A Promising Antioxidant Adjuvant Agent

2017 ◽  
Vol 34 (14) ◽  
pp. 1382-1388 ◽  
Author(s):  
Lucia Marseglia ◽  
Russel Reiter ◽  
Giuseppe Buonocore ◽  
Eloisa Gitto ◽  
Gabriella D'Angelo
Keyword(s):  
Organ Failure ◽  
Neonatal Sepsis ◽  
Current Knowledge ◽  
Clinical Problem ◽  
Multiple Organ ◽  
Organ Injury ◽  
Significant Toxicity ◽  
Major Clinical Problem

AbstractSepsis represents a major clinical problem in neonatal setting with elevated mortality rate related to multiple organ failure. Despite decades of research, the exact mechanism of organ failure in sepsis is still not completely understood. Oxidative stress (OS), derived from an imbalance between pro-oxidant and antioxidant factors, is involved in the pathogenesis of several neonatal diseases, including sepsis, and plays a particular role in systemic organ failure. Recently, it has been recognized that administration of antioxidants could be useful in septic patients. Among all antioxidants, melatonin has a characteristic role as an antioxidant, anti-inflammatory, and anti-apoptotic agent. In combination with other interventions, melatonin may contribute to an improvement in septic organ injury. Furthermore, melatonin has already been widely used in treating various diseases of neonatal population, including asphyxia, respiratory distress, and sepsis, and no significant toxicity or treatment-related side effects with long-term melatonin therapy have been reported. This review aims to summarize current knowledge concerning the potential beneficial role of melatonin in septic neonates, supporting its short-term adjuvant co-therapy to reduce complications during neonatal sepsis.

Hypersensitivity to taxol and doxil: Experimental and clinical evidence for a causal role of complement activation

2000 ◽  
Vol 49 (1-2) ◽  
pp. 71
Author(s):  
J. Szebeni ◽  
L. Baranyi ◽  
S. Savay ◽  
A.A. Chanan-Khan ◽  
P. Klein ◽  
...  
Keyword(s):  
Complement Activation ◽  
Clinical Evidence ◽  
Causal Role

scholarly journals Thromboembolic complications in COVID-19 disease, a brief update

2021 ◽  
Vol 18 (1) ◽  
pp. 37-46
Author(s):  
А. Lavrentieva ◽  
S. Tsotsolis
Keyword(s):  
Therapeutic Option ◽  
Diagnostic Value ◽  
Thromboembolic Complication ◽  
Diagnostic Methods ◽  
Thromboembolic Events ◽  
Thromboembolic Complications ◽  
Specific Virus ◽  
Mechanisms Of Development ◽  
Novel Coronavirus

The role of coagulopathy in severe novel coronavirus infection remains to be clarified. Coagulopathy mechanisms can be summarised in two main pathways: inflammation-related and specific-virus related pathways. The incidence of thromboembolic events is high with pulmonary embolism being the most frequent thromboembolic complication. Low molecular weight heparin is considered the main prophylactic and therapeutic option in patients with COVID-19. Treatment of thromboembolic complications should be started without delay in all cases with certain or clinically suspected diagnosis, whether confirmed or not with specific diagnostic methods. The article reviews the following: mechanisms of development of coagulopathy in COVID-19 including those directly related to the action of the virus, the diagnostic value of biochemical markers and thromboelastography, the incidence of thromboembolic events, and approaches to the prevention and treatment of COVID-19-associated coagulopathy.

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