{"id":4512,"date":"2026-08-21T18:14:53","date_gmt":"2026-08-21T18:14:53","guid":{"rendered":"https:\/\/pge2-hypothesis.com\/?page_id=4512"},"modified":"2026-09-30T00:03:22","modified_gmt":"2026-09-30T00:03:22","slug":"landing-page-researchers-eng","status":"publish","type":"page","link":"https:\/\/pge2-hypothesis.com\/","title":{"rendered":"The PGE2 Hypothesis HOME"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-page\" data-elementor-id=\"4512\" class=\"elementor elementor-4512\">\n\t\t\t\t<div class=\"elementor-element elementor-element-1acb9d3 e-flex e-con-boxed e-con e-parent\" data-id=\"1acb9d3\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-ab9d07f elementor-widget elementor-widget-spacer\" data-id=\"ab9d07f\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-852f023 elementor-widget elementor-widget-heading\" data-id=\"852f023\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">An integrative hypothesis for Long COVID and related syndromes<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-9cd776b elementor-widget elementor-widget-spacer\" data-id=\"9cd776b\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-61e2b00 elementor-widget__width-initial elementor-widget elementor-widget-image\" data-id=\"61e2b00\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"image.default\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2405580826000786\">\n\t\t\t\t\t\t\t<img fetchpriority=\"high\" decoding=\"async\" width=\"1024\" height=\"685\" src=\"https:\/\/pge2-hypothesis.com\/wp-content\/uploads\/2026\/03\/Screenshot_20260326_223153_Chrome-1024x685.jpg\" class=\"attachment-large size-large wp-image-126\" alt=\"\" srcset=\"https:\/\/pge2-hypothesis.com\/wp-content\/uploads\/2026\/03\/Screenshot_20260326_223153_Chrome-1024x685.jpg 1024w, https:\/\/pge2-hypothesis.com\/wp-content\/uploads\/2026\/03\/Screenshot_20260326_223153_Chrome-300x201.jpg 300w, https:\/\/pge2-hypothesis.com\/wp-content\/uploads\/2026\/03\/Screenshot_20260326_223153_Chrome-768x514.jpg 768w, https:\/\/pge2-hypothesis.com\/wp-content\/uploads\/2026\/03\/Screenshot_20260326_223153_Chrome.jpg 1394w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/>\t\t\t\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t<div class=\"elementor-element elementor-element-6d1cf34 e-flex e-con-boxed e-con e-parent\" data-id=\"6d1cf34\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t<div class=\"elementor-element elementor-element-f590072 e-grid e-con-full e-con e-child\" data-id=\"f590072\" data-element_type=\"container\" data-e-type=\"container\">\n\t\t\t\t<div class=\"elementor-element elementor-element-0061212 elementor-align-center elementor-widget__width-initial elementor-mobile-align-center elementor-widget elementor-widget-button\" data-id=\"0061212\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2405580826000786\" target=\"_blank\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Full publication<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-05a5ac3 elementor-align-center elementor-mobile-align-center elementor-widget__width-initial elementor-widget elementor-widget-button\" data-id=\"05a5ac3\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/pge2-hypothesis.com\/?page_id=4801\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Condensed scientific version<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-32f21bc elementor-align-center elementor-mobile-align-center elementor-widget__width-initial elementor-widget elementor-widget-button\" data-id=\"32f21bc\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/pge2-hypothesis.com\/?page_id=4848\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Accessible summary<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-29262a5 elementor-widget elementor-widget-text-editor\" data-id=\"29262a5\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t<h3 style=\"text-align: left;\" data-start=\"2524\" data-end=\"2655\"><br \/>Could persistent PGE2 overactivity provide a bridge between acute inflammation and chronic post-acute disease?<\/h3><p style=\"text-align: left;\" data-section-id=\"nkj52m\" data-start=\"2660\" data-end=\"2686\"><strong>Four questions need to be addressed:<\/strong><\/p><p style=\"text-align: left;\">1. How could persistent PGE2 explain the subphenotypes and remarkable breadth of symptoms?\u00a0<br \/>2. How could PGE2 remain elevated?<br \/>3. How can this hypothesis be tested?<br \/>4. What are the implications of a validated hypothesis?\u00a0<strong><br \/><\/strong><\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-9148279 elementor-align-center elementor-mobile-align-center elementor-widget elementor-widget-button\" data-id=\"9148279\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"button.default\">\n\t\t\t\t\t\t\t\t\t\t<a class=\"elementor-button elementor-button-link elementor-size-sm\" href=\"https:\/\/pge2-hypothesis.com\/?page_id=5292&#038;preview_id=5292&#038;\">\n\t\t\t\t\t\t<span class=\"elementor-button-content-wrapper\">\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-button-text\">Find the proposed answers<\/span>\n\t\t\t\t\t<\/span>\n\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-8c62edd elementor-widget elementor-widget-spacer\" data-id=\"8c62edd\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-8306c1d elementor-widget elementor-widget-text-editor\" data-id=\"8306c1d\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-5c95f12 e-flex e-con-boxed e-con e-parent e-lazyloaded\" data-id=\"5c95f12\" data-element_type=\"container\" data-e-type=\"container\"><h3>Welcome to the PGE2 Hypothesis website<\/h3><p>We would like to highlight several observations from the scientific literature.<\/p><p>Triggers associated with chronic fatigue syndromes including LC\/PAIS\/ME\/CFS, whether physical or psychological stressors, are reported to stimulate PGE2 production. PGE2 is a major mediator of the \u201csickness response\u201d, producing familiar symptoms such as fever, inflammation, gastrointestinal problems, pain and fatigue.<\/p><p>PGE2 is a single signaling molecule, but it acts through four highly versatile receptors, EP1\u2013EP4, which can exert distinct and often opposing effects. Our literature review revealed that the known functions of these receptors correspond strikingly well with the diverse biological disturbances and symptomclusters reported in Long COVID (LC) and related syndromes. PubMed searches repeatedly identified roles for PGE2 in <a href=\"https:\/\/pge2-hypothesis.com\/?page_id=1165\">symptoms and comorbidities<\/a> and <a href=\"https:\/\/pge2-hypothesis.com\/?page_id=5155\">mechanisms<\/a> associated with fatigue syndromes. We therefore propose that PGE2 may remain persistently upregulated in patients who develop LC or other chronic fatigue syndromes.<\/p><p>Because EP-receptor expression varies between tissues and individuals, different expression profiles could potentially produce very <a href=\"https:\/\/pge2-hypothesis.com\/?page_id=1317\">different phenotypes<\/a>. Techniques are available to investigate the expression of all four EP receptors and determine whether such profiles differ between patients.<\/p><p>This leads to a testable hypothesis. If persistent PGE2 upregulation and altered EP-receptor expression contribute to Long COVID and related syndromes, these patterns should be detectable and should correspond to specific clinical and biological features.<\/p><p><strong>If validated, the hypothesis could help explain the variable results of clinical trials and, importantly, why a treatment may benefit one patient, have no effect in another, or even make someone worse. It could also provide molecular biomarkers for patient stratification, potentially helping to identify which treatments are most suitable for which patient subtypes.<\/strong><\/p><p>This is why we are looking for researchers interested in testing the hypothesis.<\/p><p>In brief, research shows that many hormones and other signaling molecules stimulate PGE2 production, while PGE2 can in turn modulate their production or signaling. We hypothesize that, under certain conditions, these reciprocal feedback mechanisms could contribute to persistent PGE2 upregulation, altered EP-receptor signaling, autoimmune responses, resistances, ensuing chronic PGE2 upregulation and chronic illness.<\/p><p>The scientific basis and references for this hypothesis are presented in our recently <a class=\"decorated-link\" href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2405580826000786\" target=\"_new\" rel=\"noopener\" data-start=\"742\" data-end=\"830\">published article<\/a> in <em data-start=\"834\" data-end=\"871\">Biochemistry and Biophysics Report<\/em><\/p><\/div>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>An integrative hypothesis for Long COVID and related syndromes Full publication Condensed scientific version Accessible summary Could persistent PGE2 overactivity [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"","ast-site-content-layout":"full-width-container","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"disabled","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"class_list":["post-4512","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/4512","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=4512"}],"version-history":[{"count":777,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/4512\/revisions"}],"predecessor-version":[{"id":6686,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/4512\/revisions\/6686"}],"wp:attachment":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4512"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}