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1.
Int J Hematol ; 116(1): 55-59, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1877965

ABSTRACT

Autoimmune and complement-related hematological side effects have been observed with messenger ribonucleic acid (mRNA) vaccines. Here, we report the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). We reviewed the medical records of seventeen patients with PNH visiting the University of Tsukuba Hospital who had received two doses of the SARS-CoV-2 mRNA vaccine between May 2021 and November 2021. Twelve patients were being treated with complement inhibitors. The median age of all patients was 62 years (range 29-89 years).; six were males and eleven were females. Fourteen patients received the BNT162b2 vaccine (Pfizer/BioNTech) and three received the mRNA-1273 vaccine (Moderna). The median percentages of PNH clones in erythrocytes and granulocytes were 37.61% (range 8.11-85.71%) and 59.73% (range 3.76-97.82%), respectively. Of the twelve patients receiving complement inhibitors, only one had a hemolytic reaction after vaccination, but it did not meet the definition of breakthrough hemolysis. By contrast, hemolytic attacks were observed in two of the five untreated patients with PNH, and one of them required a blood transfusion. Appropriate administration of complement inhibitors to patients with PNH may prevent hemolysis induced by SARS-CoV-2 mRNA vaccination.


Subject(s)
COVID-19 Vaccines , COVID-19 , Hemoglobinuria, Paroxysmal , Hemolysis , 2019-nCoV Vaccine mRNA-1273/adverse effects , Adult , Aged , Aged, 80 and over , BNT162 Vaccine/adverse effects , COVID-19/complications , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Complement Inactivating Agents/therapeutic use , Female , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/drug therapy , Humans , Male , Middle Aged , SARS-CoV-2 , Vaccination/adverse effects
2.
Front Immunol ; 12: 712572, 2021.
Article in English | MEDLINE | ID: covidwho-1472386

ABSTRACT

The complement system is central to first-line defense against invading pathogens. However, excessive complement activation and/or the loss of complement regulation contributes to the development of autoimmune diseases, systemic inflammation, and thrombosis. One of the three pathways of the complement system, the alternative complement pathway, plays a vital role in amplifying complement activation and pathway signaling. Complement factor D, a serine protease of this pathway that is required for the formation of C3 convertase, is the rate-limiting enzyme. In this review, we discuss the function of factor D within the alternative pathway and its implication in both healthy physiology and disease. Because the alternative pathway has a role in many diseases that are characterized by excessive or poorly mediated complement activation, this pathway is an enticing target for effective therapeutic intervention. Nonetheless, although the underlying disease mechanisms of many of these complement-driven diseases are quite well understood, some of the diseases have limited treatment options or no approved treatments at all. Therefore, in this review we explore factor D as a strategic target for advancing therapeutic control of pathological complement activation.


Subject(s)
Complement Factor D/antagonists & inhibitors , Complement Pathway, Alternative/drug effects , Molecular Targeted Therapy , Adipose Tissue/metabolism , Aging/immunology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Complement Factor D/biosynthesis , Complement Factor D/deficiency , Complement Factor D/physiology , Energy Metabolism , Geographic Atrophy/genetics , Geographic Atrophy/immunology , Hemoglobinuria, Paroxysmal/drug therapy , Hemoglobinuria, Paroxysmal/genetics , Hemoglobinuria, Paroxysmal/immunology , Hepatocytes , Humans , Kidney Diseases/immunology , Liver/injuries , Oligonucleotides, Antisense/therapeutic use , Peptides, Cyclic/therapeutic use , Phagocytosis
3.
Hamostaseologie ; 41(5): 397-399, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1428942

ABSTRACT

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired clonal haematological disease characterized by complement-mediated haemolysis, bone marrow failure and venous thrombosis. Anticomplement therapy eculizumab improves survival and reduces complications. Severe acute respiratory distress syndrome corona virus 2 (SARS-CoV-2) disease 2019 (COVID-19) is associated with high incidence of both venous and arterial thrombosis in hospitalized patients with pneumonia. Deep venous thrombosis (DVT) as the presenting symptom of COVID-19 is a rare event. We describe a well-controlled PNH patient on eculizumab for more than 5 years who presented with DVT, while on warfarin, as the first sign of COVID-19. To our knowledge, this is the first described case of DVT in a PNH patient with COVID-19.


Subject(s)
COVID-19/complications , COVID-19/diagnosis , Hemoglobinuria, Paroxysmal/complications , SARS-CoV-2 , Venous Thrombosis/complications , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Anticoagulants/therapeutic use , Complement Inactivating Agents/therapeutic use , Hemoglobinuria, Paroxysmal/drug therapy , Humans , Male , Venous Thrombosis/diagnosis , Warfarin/therapeutic use
4.
Medicine (Baltimore) ; 100(20): e25456, 2021 May 21.
Article in English | MEDLINE | ID: covidwho-1324829

ABSTRACT

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, life-threatening hemopoietic stem cell disorder characterized by the triad of hemolytic anemia, thrombosis, and impaired bone marrow function. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. PATIENT CONCERNS: A 27-year-old Caucasian man with PNH presented to the Emergency Department of our hospital with acute onset shortness of breath, cough and blood in urine. DIAGNOSIS: The patient was diagnosed with acute hemolytic exacerbation of PNH complicated with moderate COVID19 pneumonia. OUTCOMES: The patient was initiated with an anticoagulant unfractionated heparin, dexamethasone, and cefuroxime injection. His symptoms quickly resolved, and he was discharged after 5 days. CONCLUSION: The complement system activation is a critical component in the sequalae of COVID19 infection. Evidence suggests that severe outcomes in COVID19 infection are attributed to the excessive activation of the complement cascade leading to acute lung injury and associated is with an increased prothrombotic state. Notably, C5a concentration was noted to be higher in patients with COVID19 infection. The use of complement inhibitors to attenuate immune mediated damage in COVID19 nevertheless represents a very interesting theoretical approach. However, careful consideration as to which patients may benefit will be required and the outcome of clinical trials needed.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Complement Inactivating Agents/administration & dosage , Hemoglobinuria, Paroxysmal/complications , Thrombosis/prevention & control , Adult , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , COVID-19 Serological Testing , Complement Activation/drug effects , Hemoglobinuria, Paroxysmal/blood , Hemoglobinuria, Paroxysmal/drug therapy , Hemoglobinuria, Paroxysmal/immunology , Humans , Male , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Symptom Flare Up , Thrombosis/immunology , Treatment Outcome
9.
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
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