Complement and Thromboinflammation in SARS-CoV-2:
When our adaptive immune system fails or responds too slow in pandemics, we need to be able to rely on our host defense and innate immune system. It has not only become more relevant for now, but also for future infections. As within the current SARS-CoV-2 / Covid-19 pandemic it is evident that the innate immune system has a pivotal role in relation to the inflammatory storm in SARS-CoV-2 infected patients. Hyper activation is contributing to lung damage, as well as microvascular injury of the thromboinflammation pathway is observed. We are looking both at the hyperinflammation in which complement appears to play a role, as well as the microvascular endothelial cell injury and pulmonary angioedema in which the kinin pathway plays a role. Hycult Biotech is developing unique reagents as a niche player within Innate Immunity. Our main goal is translating scientific tools into biomarkers for disease activity or validation of biomarkers by actively participating in scientific projects. For this purpose Hycult Biotech engages in a number of recent SARS-CoV-2 initiatives to unravel the inflammatory process and validate biomarkers that are supportive for therapeutic interventions.
SARS-CoV-2 studies on complement therapeutics:
- Eculizumab (Soliris) in Covid-19 Infected Patients (SOLID-C19)
- Alexion to study Ultomiris for Covid-19 treatment
- The first case of COVID-19 treated with the complement C3 inhibitor AMY-101.
- InflaRx starts dosing Covid-19 patients in Europe
- Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation
- Case study China in which 2 patients responded to anti-C5a from Inflarx Germany. In this experimental assay set up with our old MBL/MASP2 activation assay.
- Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases.
- Coronaviruses hijack the complement system
- Complement as a target in COVID-19?
- Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis Previous viral infections MERS-CoV and SARS-CoV studied. C3-/- deficient mice are protected against acute respiratory syndrome. Anaphylatoxins C3a, C4a and C5a are damaging in lungs. Inhibiting anti-C3a in mouse models appeared to be effective.
- Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV Inhibition of complement activation with an anti-C5aR Ab reduces systemic and local inflammatory responses.
- Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV Inhibiting C5aR1 Reduces Inflammation in Mice Infected with MERS-CoV
Thromboinflammation / Lung injury related
- Kinins and Cytokines in COVID-19: A Comprehensive Pathophysiological Approach
- Thrombomodulin in disseminated intravascular coagulation and other critical conditions—a multi-faceted anticoagulant protein with therapeutic potential:
- Soluble Thrombomodulin Increases in Patients with Disseminated Intravascular Coagulation and in Those with Multiple Organ Dysfunction Syndrome after Trauma: Role of Neutrophil Elastase
- Thrombomodulin favors leukocyte microvesicle fibrinolytic activity, reduces NETosis and prevents septic shock-induced coagulopathy in rats