The initiator and first author, Vjera Ramer, began her literature research following personal, long-standing experiences with puzzling medication interactions. In the scientific literature, she encountered converging evidence suggesting that her diverse symptoms might potentially be explained by increased activity of a single signaling molecule: prostaglandin E2 (PGE2).

During her literature searches she found that PGE2 is involved not only in the symptoms of acute infections such as COVID-19, but also in many of the biological processes and clinical manifestations observed in other post-acute infection syndromes (PAIS) and the fatigue syndromes ME/CFS. She also found that PGE2 production is stimulated by a wide range of other signaling molecules. This led her to hypothesize that PGE2 may not only be an important regulator of acute inflammatory responses, but may also play a central role in chronic inflammation through self-reinforcing feedback mechanisms in which pro-inflammatory mediators amplify one another.

While the prevailing view considers paracrine signaling molecules to act primarily locally, she found reasons to propose that PGE2 may also exert systemic effects. PGE2 is produced by virtually all cells and can induce body-wide responses, such as fever. From this perspective, she developed the hypothesis that PGE2, in interaction with endocrine hormones and other signaling molecules, may play a key role in post-infectious symptoms. Long COVID represents the most extensively investigated example in this framework.

Driven by the potential significance of these observations, she spent three years intensively studying the scientific literature on endocrine-paracrine regulatory mechanisms. Based on this work, she developed the PGE2 hypothesis for Long COVID into a scientific article, inspired and supported by former internist and researcher Gert van Montfrans. The article was recently published in a biochemical journal indexed on ScienceDirect, “Biochemistry and Biophysics Reports”.

For further information, please contact Vjera Ramer at: the.pge2hypothesis@proton.me