Inhibition of the lectin pathway of complement ameliorates hypocomplementemia and restores serum bactericidal activity in patients with severe COVID‐19

Lynch, Nicholas J.; Chan, Andrew; Ali, Youssif M.; Khatri, Priyanka; Bamigbola, Ifeoluwa E; Demopulos, Gregory; Paganessi, Muriel; Schwaeble, Wilhelm

doi:10.1002/ctm2.980

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…Though untested for thrombotic microangiopathy lesions in IgAN, narsoplimab showed promise in other conditions, including COVID-19. 65 , 66 …”

Section: Discussionmentioning

confidence: 99%

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Ștefan,

Alamartine,

Mariat

et al. 2024

Kidney International Reports

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“…Though untested for thrombotic microangiopathy lesions in IgAN, narsoplimab showed promise in other conditions, including COVID-19. 65 , 66 …”

Section: Discussionmentioning

confidence: 99%

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Ștefan,

Alamartine,

Mariat

et al. 2024

Kidney International Reports

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“…Narsoplimab was shown to improve lung function and laboratory markers and reduce overall disease severity and mortality [ 28 ]. All patients in this study likely had SARS-CoV-2–specific antibodies, as the detection of covalently bound C1s/C1Inh complexes indicates that the CP was activated [ 26 ]. It is unknown at present to what extent CP-driven activation of complement by SARS-CoV-2–specific antibodies contributes to COVID-19 pathology [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…All patients in this study likely had SARS-CoV-2–specific antibodies, as the detection of covalently bound C1s/C1Inh complexes indicates that the CP was activated [ 26 ]. It is unknown at present to what extent CP-driven activation of complement by SARS-CoV-2–specific antibodies contributes to COVID-19 pathology [ 26 ]. As inhibition of MASP-2 functional activity alone achieved significant recovery from hypocomplementemia, the LP and not the CP appears to be primarily responsible for the massive consumption of complement components in patients with acute COVID-19.…”

Section: Discussionmentioning

confidence: 99%

“…The presence of thrombotic microangiopathies and the deposition of complement activation products in injured tissues and organs, including C5b-9, C3d, C4d, and MASP-2, implied the involvement of LP and CP activation in severe COVID-19 [ 25 ]. Several reports showed elevation of complement C5a and soluble C5b-9 in sera from patients with COVID-19, indicating activation of complement during SARS-CoV-2 infection [ 22 , 23 , 26 , 27 ]. Such findings have led to the trial of complement therapeutics in the treatment of patients who are critically ill with COVID-19.…”

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confidence: 99%

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Inhibition of the Lectin Pathway of Complement Activation Reduces Acute Respiratory Distress Syndrome Severity in a Mouse Model of SARS-CoV-2 Infection

Ali,

Carnell,

Fumagalli

et al. 2023

The Journal of Infectious Diseases

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Most COVID-19 patients requiring ICU care develop an acute respiratory distress syndrome (ARDS), characterised by severe hypoxemia, decreased lung compliance, and high vascular permeability. Activation of the complement system is a hallmark of moderate and severe COVID-19, with abundant deposition of complement proteins reported in inflamed tissue and on the endothelium during COVID-19. Using a transgenic mouse model of SARS-CoV-2 infection we assessed the therapeutic utility of an inhibitory antibody (HG4) targeting the lectin pathway key enzyme MASP-2. Treatment of infected mice with HG4 reduced the disease severity score and improved survival compared to mice that received an isotype control antibody. Administration of HG4 significantly reduced the lung injury score including alveolar inflammatory cell infiltration, alveolar oedema and alveolar haemorrhage. The overall ameliorating effect of MASP-2 inhibition on the severity of COVID-19 pathology is reflected by a significant reduction in the pro-inflammatory activation of brain microglia in HG4 treated mice.

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“…Viral infections such as influenza A have been identified as risk factors for invasive meningococcal disease due to their ability to impair the immune response of the respiratory mucosa and promote bacterial virulence [ 2 , 10 , 13 ]. COVID-19 infection involves the activation of the lectin pathway and the spike and nucleocapsid proteins, which can directly activate the complement cascade via the lectin pathway, leading to complement consumption [ 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

Invasive Meningococcal Disease and COVID-19 Co-Infection: A Case Report

Espiche,

Beltran,

Win Lei

et al. 2023

Cureus

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This case report presents a 53-year-old male patient infected with COVID-19 who developed acute respiratory distress syndrome (ARDS) and septic shock due to meningococcemia, despite the absence of clinical signs of meningitis. This patient's condition was complicated by pneumonia in the setting of myocardial failure. In the curse of the disease, it is remarked that the importance of early recognition of sepsis symptoms is crucial in distinguishing patients with COVID-19 from those with other infections and preventing fatal outcomes. The case presented an excellent opportunity to review meningococcal disease's intrinsic and extrinsic risk factors. With the identified risk factors, we propose different measures to be considered to diminish and recognize this fatal disease early.

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Inhibition of the lectin pathway of complement ameliorates hypocomplementemia and restores serum bactericidal activity in patients with severe COVID‐19

Cited by 6 publications

References 11 publications

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

Inhibition of the Lectin Pathway of Complement Activation Reduces Acute Respiratory Distress Syndrome Severity in a Mouse Model of SARS-CoV-2 Infection

Invasive Meningococcal Disease and COVID-19 Co-Infection: A Case Report

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