COVID-19: A collision of complement, coagulation and inflammatory pathways, 2020, Chauhan et al

Abstract
COVID-19 is frequently accompanied by a hypercoagulable inflammatory state with microangiopathic pulmonary changes that can precede the diffuse alveolar damage characteristic of typical acute respiratory distress syndrome (ARDS) seen in other severe pathogenic infections. Parallels with systemic inflammatory disorders such as atypical hemolytic uremic syndrome (aHUS) have implicated the complement pathway in the pathogenesis of COVID-19, and particularly the anaphylatoxins C3a and C5a released from cleavage of C3 and C5, respectively. C5a is a potent cell signalling protein that activates a cytokine storm—a hyper-inflammatory phenomenon—within hours of infection and the innate immune response. However, excess C5a can result in a pro-inflammatory environment orchestrated through a plethora of mechanisms that propagate lung injury, lymphocyte exhaustion, and an immune paresis. Furthermore, disruption of the homeostatic interactions between complement and extrinsic and intrinsic coagulation pathways contributes to a net pro-coagulant state in the microvasculature of critical organs.

Fatal COVID-19 has been associated with a systemic inflammatory response accompanied by a pro-coagulant state and organ damage, particularly microvascular thrombi in the lungs and kidneys. Pathologic studies report strong evidence of complement activation. C5 blockade reduces inflammatory cytokines and their manifestations in animal studies, and has shown benefits in patients with aHUS, prompting investigation of this approach in the treatment of COVID-19. This review describes the role of the complement pathway and particularly C5a and its aberrations in highly pathogenic virus infections, and therefore its potential as a therapeutic target in COVID-19.
 
C5a, a terminal product of the complement system, can, by itself, promote blood vessel dysfunction and the subsequent formation of blood clots seen in people with atypical hemolytic uremic syndrome (aHUS), a study shows.


Notably, the same C5a-induced molecular mechanisms were detected among patients with severe COVID-19 and whose infection triggered complement system activation.


These findings highlight C5a as a common blood clotting-inducer in diseases characterized by an overly active complement system and suggest that suppressing C5a may be a new and improved therapeutic approach for such conditions, according to the researchers.

In contrast to the approved complement-suppressing therapy Soliris (eculizumab) — which prevents C5 from being cleaved into C5a and C5b — blocking C5a would preserve the formation of C5b-9, a complex made of C5a and other proteins that is critical in controlling bacterial infections, the team said.


Notably, Tavneos (avacopan), a C5a-suppressing oral therapy from ChemoCentryx, has been approved as an add-on treatment for ANCA-associated vasculitis (AAV), a rare condition associated with an overly active complement system.
 
I'm not sure how relevant this is, but my mom's cousin died from ANCA vasculitis this summer. For decades, it was assumed she had lupus. After she got Covid-19, her health went downhill rapidly. She had multiple hospitalizations and intubations due to pneumonia in rapid succession. Finally, the doctors discovered she had ANCA vaculitis and postulated she was misdiagnosed with lupus her whole life. But by the time they recognized her condition and how to treat it, she could no longer tolerate being severely sick and in and out of the hospital, so she elected to withdraw treatment and die.
 
https://www.vasculitis.org.uk/about-vasculitis/what-is-anca


ANCA-associated vasculitis
If a patient has ANCA-associated vasculitis, he or she may have one of three different vasculitis conditions: 1. granulomatosis with polyangiitis (GPA), previously known as Wegener’s granulomatosis, 2. Microscopic polyangiitis (MPA) and 3. eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome (1). These three conditions are grouped together under the umbrella term ‘ANCA-associated vasculitis’ because they are all associated with a key protein factor in the blood called ‘ANCA’ and because they all cause inflammation or damage to small blood vessels. Small blood vessels are found all over the human body, so any part of the body can be affected, but most commonly the kidneys, lungs, joints, ears, nose, and nerves. Because the kidneys and lungs are vital organs, early treatment for ANCA-associated vasculitis is very important to prevent serious organ damage.
 
Is long covid and mecfs more like a light aHUS with CNS involvement

https://ahusnews.com/news/ahus-extra-renal-manifestations-most-common-cns/
Although the kidneys are the main target in patients with aHUS, the disorder may also affect the lungs, skin, CNS — brain and spinal cord — and the gastrointestinal tract.

They used to use plasma exchange in aHUS but it didn’t work so well
 
Last edited:
I had my complement results
Normal c3
C4 lowest normal associated with lupus and rheumatoid arthritis
 
Last edited:
You must log in or register to reply here.
Back
Top Bottom