This, again, supports our position that COVID-19, Long COVID (PACS), and PACVS are fundamentally Gq/11-linked signalling disorders, because both major receptor arms discussed here, Ang II/AT1R and Ang-(1-7)/MAS1, involve Gq/11-coupled signalling.
Autoantibodies against ACE2, MAS1, and related RAS components could therefore disturb vascular tone, calcium signalling, endothelial function, inflammation, edema, bruising, cardiovascular symptoms, and neurovegetative regulation through persistent dysregulation of Gq/11-linked pathways.
In the case of PACVS, there are at least three possible contributors: spike protein (S), lipid nanoparticles (LNP), and endotoxin (adjuvant). All converge on pathways that affect Gq/11 signalling, calcium mobilization, endothelial function, vascular tone, platelet activity, mast-cell activation, and inflammatory amplification.
The new Italian study also links directly to previous research from Germany, which found functional autoantibodies against AT1 and MAS1 receptors in over 90% of the investigated COVID-19 patient sera (29/31) (Wallukat et al., 2021).
Of course, Chinese research conducted after the first SARS outbreak in 2002/2003 identified ARDS as a Gq/11-driven disease.
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Wallukat G, Hohberger B, Wenzel K, Fürst J, Schulze-Rothe S, Wallukat A, Hönicke AS, Müller J - "Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms" J Transl Autoimmun 4:100100 (2021) doi: 10.1016/j.jtauto.2021.100100
https://www.sciencedirect.com/science/a ... 9021000204
Bellavite P, Di Fede G, Mantovani M, Zanolin E - "Autoimmune Features of Post-COVID-19 Vaccination Syndrome and Their Impacts on the Renin–Angiotensin System" Vaccines 14(4):354 (2026)
https://doi.org/10.3390/vaccines14040354
Abstract
One of the most critical aspects of post-acute COVID-19 syndrome (PACS) and post-acute COVID-19 vaccination syndrome (PACVS) is the presence of autoantibodies. These autoantibodies are directed against various receptors in the autonomic and cardiovascular systems, including those targeting proteins of the renin–angiotensin system (RAS). The RAS plays a central role in regulating vascular homeostasis, inflammation, and endothelial function. During SARS-CoV-2 infection, the interaction of the spike (S) protein with angiotensin-converting enzyme 2 (ACE2) can alter the balance of the RAS, favoring an imbalance towards the ACE/Angiotensin II/AT1R axis, known for its pro-inflammatory, pro-thrombotic, and vasoconstrictive properties. Similar pathological mechanisms also come into play in response to vaccinations that use the S protein as an antigen. Studies conducted by other groups and us on patients with PACS and PACVS have revealed the presence of autoantibodies directed against these RAS components and the mechanisms by which these antibodies can worsen the clinical situation. In particular, anti-ACE2, presumably formed by the anti-idiotype network or molecular mimicry, is correlated with PACVS symptoms in many patients. Furthermore, the presence of anti-MAS1 antibodies can reduce the efficiency of the ACE2/Angiotensin-(1–7)/MAS1 axis, which normally acts as a counter-regulator. Considering this evidence, an analysis of RAS molecules and the autoantibodies implicated in reactions to them may be useful for evaluating a state of persistent dysregulation associated with post-vaccination symptoms such as asthenia, headache, skin edema and bruising, cardiovascular alterations, and neurovegetative manifestations. Finally, we offer insights into diagnosing these multifaceted syndromes and working hypotheses to guide research into possible therapeutic approaches.