Many hormones stimulate PGE2 production, while PGE2 in turn counteracts the actions of these hormones, presumably to prevent excessive hormonal activity. Under certain conditions, however, markedly elevated PGE2 levels could lead to persistent homeostatic imbalance and hormonal multiresistance.

PGE2 may antagonize the receptor-mediated actions of other mediators through four mechanisms:

1. Inhibition of secretion: PGE2 can inhibit the release of, among others, acetylcholine, insulin, dopamine and serotonin (via EP3).
2. Receptor phosphorylation: PGE2 stimulates phosphorylation processes that may interfere with the binding of other substances to their receptors (via EP1).
3. Autoimmunity: PGE2 promotes the production and class switching (from IgM to IgG) of functional autoantibodies against G-protein-coupled receptors (GPCRs) and hormone receptors (via EP2 and EP4).
4. Signaling interference: Because EP receptors are GPCRs, PGE2 may compete with other GPCR-activating hormones within intracellular signalling pathways for a finite pool of intracellular signaling molecules (via EP1–EP4).

This could potentially help explain why Long COVID patients exhibit symptoms suggestive of resistance to, among others, AVP (excessive thirst), insulin (glucose dysregulation) and leptin (metabolic dysregulation).