Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
1.
Nephron ; 146(2): 197-202, 2022.
Article in English | MEDLINE | ID: covidwho-1528608

ABSTRACT

SARS-CoV-2 causes thrombotic microangiopathy (TMA) through the activation of an alternative and lectin complement pathway. TMA is one of the main reasons for acute kidney injury development in patients with COVID-19. In this study, we present 3 TMA cases with severe kidney injury triggered by SARS-CoV-2. In the absence of other TMA causes, we diagnosed the atypical hemolytic uremic syndrome, triggered by SARS-CoV-2 due to abnormal complement activation. Because of both coagulation factors activation, and the high level of D-dimer in patients with COVID-19, it is crucial to differentiate disseminated intravascular coagulation from TMA. The use of anticomplement therapies such as eculizumab should be considered in refractory cases of progressive COVID-19. Controlled clinical trials are required before a definitive statement can be made.


Subject(s)
COVID-19/complications , Thrombotic Microangiopathies/etiology , Adult , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/virology , Complement Inactivating Agents/therapeutic use , Female , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification , Thrombotic Microangiopathies/drug therapy
2.
Front Immunol ; 12: 680567, 2021.
Article in English | MEDLINE | ID: covidwho-1304591

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. A clinical series of Kawasaki-like multisystem inflammatory syndrome (MIS), occurring after SARS-CoV-2 infection, have been described in children (MIS-C) and adults (MIS-A), but the pathophysiology remains unknown. CASE PRESENTATION: We describe a case of post-COVID-19 MIS-A in a 46-year-old man with biopsy-proven renal thrombotic microangiopathy (TMA). Specific complement inhibition with eculizumab was initiated promptly and led to a dramatic improvement of renal function. CONCLUSION: Our case suggests that that TMA could play a central role in the pathophysiology of post-COVID-19 MIS-A, making complement blockers an interesting therapeutic option.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/diagnosis , Complement Inactivating Agents/therapeutic use , Kidney/metabolism , SARS-CoV-2/physiology , Systemic Inflammatory Response Syndrome/diagnosis , Thrombotic Microangiopathies/diagnosis , COVID-19/drug therapy , Humans , Kidney/pathology , Male , Middle Aged , Pandemics , Recovery of Function , Systemic Inflammatory Response Syndrome/drug therapy , Thrombotic Microangiopathies/drug therapy
3.
J Pediatr Hematol Oncol ; 44(1): e237-e240, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-998557

ABSTRACT

Influenza virus can trigger atypical hemolytic uremic syndrome and present with complement-driven thrombotic microangiopathy (TMA). When administered promptly, complement-blocking therapies can spare organ injury and be lifesaving. However, diagnosing TMA in the setting of a severe viral infection can be challenging, as a significant overlap of symptoms and disease complications exists. This is particularly true in influenza virus infections and more recently, Coronavirus disease 2019 (COVID-19) infections. We present a 16-year-old male with H1N1 influenza-induced atypical hemolytic uremic syndrome who quickly improved with complement-blocking therapy, highlighting an urgent need to include TMA in the differential diagnosis of severe viral infections.


Subject(s)
Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/complications , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/virology , Adolescent , Antibodies, Monoclonal, Humanized/therapeutic use , Complement Inactivating Agents/therapeutic use , Humans , Influenza, Human/blood , Influenza, Human/diagnosis , Male , Thrombotic Microangiopathies/blood , Thrombotic Microangiopathies/drug therapy
4.
Nat Rev Cardiol ; 18(3): 194-209, 2021 03.
Article in English | MEDLINE | ID: covidwho-936141

ABSTRACT

The core pathology of coronavirus disease 2019 (COVID-19) is infection of airway cells by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that results in excessive inflammation and respiratory disease, with cytokine storm and acute respiratory distress syndrome implicated in the most severe cases. Thrombotic complications are a major cause of morbidity and mortality in patients with COVID-19. Patients with pre-existing cardiovascular disease and/or traditional cardiovascular risk factors, including obesity, diabetes mellitus, hypertension and advanced age, are at the highest risk of death from COVID-19. In this Review, we summarize new lines of evidence that point to both platelet and endothelial dysfunction as essential components of COVID-19 pathology and describe the mechanisms that might account for the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19. We highlight the distinct contributions of coagulopathy, thrombocytopathy and endotheliopathy to the pathogenesis of COVID-19 and discuss potential therapeutic strategies in the management of patients with COVD-19. Harnessing the expertise of the biomedical and clinical communities is imperative to expand the available therapeutics beyond anticoagulants and to target both thrombocytopathy and endotheliopathy. Only with such collaborative efforts can we better prepare for further waves and for future coronavirus-related pandemics.


Subject(s)
Blood Coagulation Disorders/blood , Blood Platelet Disorders/blood , COVID-19/blood , Endothelium, Vascular/physiopathology , Inflammation/blood , Thrombosis/blood , Administration, Inhalation , Anticoagulants/therapeutic use , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , Blood Coagulation Disorders/physiopathology , Blood Platelet Disorders/drug therapy , Blood Platelet Disorders/etiology , Blood Platelet Disorders/physiopathology , COVID-19/complications , COVID-19/drug therapy , COVID-19/physiopathology , Endothelium-Dependent Relaxing Factors/therapeutic use , Epoprostenol/therapeutic use , Heart Disease Risk Factors , Humans , Iloprost/therapeutic use , Inflammation/etiology , Inflammation/physiopathology , Nitric Oxide/therapeutic use , Platelet Aggregation Inhibitors/therapeutic use , SARS-CoV-2 , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/drug therapy , Systemic Inflammatory Response Syndrome/physiopathology , Thrombosis/etiology , Thrombosis/immunology , Thrombotic Microangiopathies/blood , Thrombotic Microangiopathies/drug therapy , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/physiopathology , Vascular Diseases/blood , Vascular Diseases/drug therapy , Vascular Diseases/etiology , Vascular Diseases/physiopathology , Vasodilator Agents/therapeutic use , Venous Thromboembolism/blood , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/physiopathology
5.
J Clin Invest ; 130(11): 5674-5676, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-760323

ABSTRACT

In a stunningly short period of time, the unexpected coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has turned the unprepared world topsy-turvy. Although the rapidity with which the virus struck was indeed overwhelming, scientists throughout the world have been up to the task of deciphering the mechanisms by which SARS-CoV-2 induces the multisystem and multiorgan inflammatory responses that, collectively, contribute to the high mortality rate in affected individuals. In this issue of the JCI, Skendros and Mitsios et al. is one such team who report that the complement system plays a substantial role in creating the hyperinflammation and thrombotic microangiopathy that appear to contribute to the severity of COVID-19. In support of the hypothesis that the complement system along with neutrophils and platelets contributes to COVID-19, the authors present empirical evidence showing that treatment with the complement inhibitor compstatin Cp40 inhibited the expression of tissue factor in neutrophils. These results confirm that the complement axis plays a critical role and suggest that targeted therapy using complement inhibitors is a potential therapeutic option to treat COVID-19-induced inflammation.


Subject(s)
Betacoronavirus/metabolism , Complement Activation/drug effects , Coronavirus Infections , Pandemics , Peptides, Cyclic/pharmacology , Pneumonia, Viral , Thromboplastin/biosynthesis , Thrombotic Microangiopathies , Blood Platelets/metabolism , Blood Platelets/pathology , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Coronavirus Infections/pathology , Humans , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Inflammation/virology , Neutrophils/metabolism , Neutrophils/pathology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Pneumonia, Viral/pathology , SARS-CoV-2 , Severity of Illness Index , Thrombotic Microangiopathies/drug therapy , Thrombotic Microangiopathies/metabolism , Thrombotic Microangiopathies/pathology , Thrombotic Microangiopathies/virology
6.
Am J Case Rep ; 21: e927418, 2020 Sep 12.
Article in English | MEDLINE | ID: covidwho-761141

ABSTRACT

BACKGROUND Patients receiving immunosuppressive therapies might be more susceptible to COVID-19. Conversely, an exaggerated inflammatory response to the SARS-CoV-2 infection might be blunted by certain forms of immunosuppression, which could be protective. Indeed, there are data from animal models demonstrating that complement may be a part of the pathophysiology of coronavirus infections. There is also evidence from an autopsy series demonstrating complement deposition in the lungs of patients with COVID-19. This raises the question of whether patients on anti-complement therapy could be protected from COVID-19. CASE REPORT Case 1 is a 39-year-old woman with an approximately 20-year history of paroxysmal nocturnal hemoglobinuria (PNH), who had recently been switched from treatment with eculizumab to ravulizumab prior to SARS-CoV-2 infection. Case 2 is a 54-year-old woman with a cadaveric renal transplant for lupus nephritis, complicated by thrombotic microangiopathy, who was maintained on eculizumab, which she started several months before she developed the SARS-CoV-2 infection. Case 3 is a 60-year-old woman with a 14-year history of PNH, who had been treated with eculizumab since 2012, and was diagnosed with COVID-19 at the time of her scheduled infusion. All 3 patients had a relatively mild course of COVID-19. CONCLUSIONS We see no evidence of increased susceptibility to SARS-CoV-2 in these patients on anti-complement therapy, which might actually have accounted for the mild course of infection. The effect of anti-complement therapy on COVID-19 disease needs to be determined in clinical trials.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Complement C5/metabolism , Coronavirus Infections/complications , Hemoglobinuria, Paroxysmal/drug therapy , Pneumonia, Viral/complications , Thrombotic Microangiopathies/drug therapy , Adult , Betacoronavirus , COVID-19 , Complement C5/drug effects , Complement C5/immunology , Complement Inactivating Agents/therapeutic use , Coronavirus Infections/epidemiology , Female , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/immunology , Humans , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/immunology
7.
Immunobiology ; 225(6): 152001, 2020 11.
Article in English | MEDLINE | ID: covidwho-696536

ABSTRACT

In COVID-19, acute respiratory distress syndrome (ARDS) and thrombotic events are frequent, life-threatening complications. Autopsies commonly show arterial thrombosis and severe endothelial damage. Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. Mannan-binding lectin-associated serine protease-2 (MASP-2), the lectin pathway's effector enzyme, binds the nucleocapsid protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), resulting in complement activation and lung injury. Narsoplimab, a fully human immunoglobulin gamma 4 (IgG4) monoclonal antibody against MASP-2, inhibits lectin pathway activation and has anticoagulant effects. In this study, the first time a lectin-pathway inhibitor was used to treat COVID-19, six COVID-19 patients with ARDS requiring continuous positive airway pressure (CPAP) or intubation received narsoplimab under compassionate use. At baseline and during treatment, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed. Narsoplimab treatment was associated with rapid and sustained reduction of CEC and concurrent reduction of serum IL-6, IL-8, CRP and LDH. Narsoplimab was well tolerated; no adverse drug reactions were reported. Two control groups were used for retrospective comparison, both showing significantly higher mortality than the narsoplimab-treated group. All narsoplimab-treated patients recovered and survived. Narsoplimab may be an effective treatment for COVID-19 by reducing COVID-19-related endothelial cell damage and the resultant inflammation and thrombotic risk.


Subject(s)
Antibodies, Monoclonal/therapeutic use , COVID-19/immunology , Complement Pathway, Mannose-Binding Lectin/drug effects , Endothelium, Vascular/drug effects , SARS-CoV-2/immunology , Thrombotic Microangiopathies/drug therapy , Antibodies, Monoclonal/immunology , C-Reactive Protein/immunology , C-Reactive Protein/metabolism , COVID-19/complications , COVID-19/virology , Complement Pathway, Mannose-Binding Lectin/immunology , Endothelium, Vascular/immunology , Endothelium, Vascular/pathology , Female , Humans , Immunoglobulin G/immunology , Immunoglobulin G/therapeutic use , Inflammation/complications , Inflammation/immunology , Inflammation/prevention & control , Interleukin-6/blood , Interleukin-6/immunology , Male , Mannose-Binding Protein-Associated Serine Proteases/antagonists & inhibitors , Mannose-Binding Protein-Associated Serine Proteases/immunology , Mannose-Binding Protein-Associated Serine Proteases/metabolism , Middle Aged , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/statistics & numerical data , Retrospective Studies , SARS-CoV-2/physiology , Thrombotic Microangiopathies/complications , Thrombotic Microangiopathies/immunology
8.
Nat Rev Rheumatol ; 16(10): 581-589, 2020 10.
Article in English | MEDLINE | ID: covidwho-690837

ABSTRACT

Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number. Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA). This disorder is not typical DIC. Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome. This perspective has critical implications for treatment. Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement. Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/complications , Pneumonia, Viral/complications , Thrombosis/immunology , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Complement System Proteins/immunology , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/immunology , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/immunology , Disseminated Intravascular Coagulation/pathology , Disseminated Intravascular Coagulation/virology , Fibrinogen/analysis , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Pandemics , Plasma Exchange/methods , Platelet Count/methods , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Risk Factors , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/pathology , Thrombosis/virology , Thrombotic Microangiopathies/drug therapy , Thrombotic Microangiopathies/immunology , Thrombotic Microangiopathies/pathology , Thrombotic Microangiopathies/virology
SELECTION OF CITATIONS
SEARCH DETAIL