Beur schreef op 21 mei 2020 10:51:
Verdere theoretische ondersteuning vanuit Spanje voor hetgeen waar Osthoff in Bazel mee bezig is: C1-INH and the contact system in COVID-19-associated coagulopathy Timothy M Thomson1,2*, Emily Toscano3 , Ernesto Casis4 and Rosanna Paciucci3,4 1.
Barcelona Institute for Molecular Biology, National Science.
Thx Monacochick. (9.16u) .
Zoals ik het nu - heel voorzichtig en voorlopig ! - inschat , denk ik dat men het bij de wat lichtere Covid19 patiënten toch eerst gaat proberen met anti-stollingsmedicatie zoals de makkelijk verkrijgbare en goedkope Heparine en bij bewezen effectiviteit bij de ernstiger gevallen HAE-medicatie als Ruc kan inzetten.
"Although a similar association has not been made between C1-INH deficiency and coagulopathies, we suggest that in pathophysiological scenarios with concomitant activation of the extrinsic pathway, such as in COVID-19, C1-INH could play a protective role. C1-INH replacement therapy has long been used in acute and prophylactic treatment of HAE36, and could be useful in the management of COVID-19-associated coagulopathy.
Further, heparin and sulfated glycans amplify the inhibitory functions of C1-INH on the contact system37, which, in addition to the activities of heparin on coagulation factors, could help explain the beneficial effects of heparin in the management of COVID-19 patients.
Conclusions
Unlike all currently prevailing hypotheses, which focus on non-pathogenspecific mechanisms, we propose a pathogen-specific mechanism by which non-structural SARS-CoV proteins bind to C1 esterase inhibitor (C1-INH, encoded by SERPING1), potentially causing a deficiency in this regulator of the contact and complement systems. Although it requires experimental confirmation, such as protein-protein binding and C1-INH enzymatic assays, the plausibility of our hypothesis is supported by the multiplicity of interactions observed between CoV proteins and C1-INH. Importantly, our hypothesis provides a single mechanism that explains many clinical, pathological and laboratory findings associated with severe COVID-19 and opens up a whole
new set of therapeutic options to tackle the most deadly manifestations of this viral disease"