{"id":1476,"date":"2026-04-07T02:24:00","date_gmt":"2026-04-07T02:24:00","guid":{"rendered":"https:\/\/pge2-hypothesis.com\/?page_id=1476"},"modified":"2026-08-26T06:05:01","modified_gmt":"2026-08-26T06:05:01","slug":"1476-2","status":"publish","type":"page","link":"https:\/\/pge2-hypothesis.com\/?page_id=1476","title":{"rendered":"Hypothetical biomarkers"},"content":{"rendered":"\t\t
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Hypothetical biomarkers for two presumed categories of LC patients: \u201cEP3-up\u201d and \u201cEP3-down\u201d<\/h2>\t\t\t\t<\/div>\n\t\t\t\t
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The table below lists reported biomedical characteristics of Long COVID patients that are consistent with PGE2 activity associated with either an \u201cEP3-up\u201d or \u201cEP3-down\u201d profile, according to the literature.<\/p>\n

Candidate biomarkers for two subgroups of LC patients based on the PGE2 hypothesis<\/h3>\n

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\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Hypothetical biomarkers for<\/strong><\/p>\n

LC Category A – \u201cEP3 up\u201d<\/p>\n

enhanced capacity of EP3 as compared to healthy subjects<\/p>\n

\u201cseropositive Long COVID\u201d<\/p>\n<\/td>\n

\n

Hypothetical biomarkers for<\/strong><\/p>\n

LC Category B – \u201cEP3 down\u201d<\/p>\n

insufficient capacity of EP3 as compared to healthy subjects<\/p>\n

\u201cseronegative Long COVID\u201d<\/p>\n<\/td>\n

\n

References<\/strong><\/p>\n<\/td>\n<\/tr>\n

\u00a0<\/td>\n<\/tr>\n
Data compared to presumed category B patients:<\/strong><\/td>\nData compared to presumed category A patients:<\/strong><\/td>\n\u00a0<\/td>\n<\/tr>\n
higher percentage was hospitalized for COVID-19<\/td>\nhigher percentage experienced a mild infection<\/td>\n\u00a0 11<\/sup><\/a><\/td>\n<\/tr>\n
higher percentage of male patients<\/td>\nhigher percentage of female patients<\/td>\n\u00a0 11<\/sup><\/a>,<\/sup>150<\/sup><\/a><\/td>\n<\/tr>\n
more antibodies against Sars<\/td>\nless antibodies against Sars<\/td>\n153<\/sup><\/a> 159<\/sup><\/a>,<\/sup>160<\/sup><\/a><\/td>\n<\/tr>\n
more activity of CD4+ cells<\/td>\nless activity of CD4+ cells 161<\/sup><\/a><\/td>\n153<\/sup><\/a><\/td>\n<\/tr>\n
more proinflammatory activity<\/td>\nmore anti-inflammatory activity<\/td>\n153<\/sup><\/a><\/td>\n<\/tr>\n
more sympathetic activity<\/td>\nless sympathetic activity<\/td>\n52<\/sup><\/a><\/td>\n<\/tr>\n
can develop a high fever<\/td>\nnot prone to high fever<\/td>\n51<\/sup><\/a>,<\/sup>162<\/sup><\/a><\/td>\n<\/tr>\n
higher blood pressure
– measured in adolescence (before age-induced changing PGE2 levels that could stimulate BP and atherosclerosis)<\/td>\n		lower blood pressure
– measured in adolescence (before age-induced changing PGE2 levels that could stimulate BP and atherosclerosis)<\/td>\n		22<\/sup><\/a>,<\/sup>163<\/sup><\/a><\/td>\n<\/tr>\n
more thrombotic problems<\/td>\nless thrombotic problems<\/td>\n164<\/sup><\/a><\/td>\n<\/tr>\n
less lipolysis, more evenly distributed (brown) adipose tissue 126<\/sup><\/a><\/td>\nmore lipolysis leading to more ectopic adipose tissue 165<\/sup><\/a><\/td>\n166<\/sup><\/a><\/td>\n<\/tr>\n
more insulin sensitivity<\/td>\nless insulin sensitivity<\/td>\n165<\/sup><\/a><\/td>\n<\/tr>\n
attenuated insulin secretion<\/td>\ninsulin secretion is less attenuated<\/td>\n167<\/sup><\/a><\/td>\n<\/tr>\n
less \u03b2-cell proliferation and survival<\/td>\nmore \u03b2-cell proliferation and survival<\/td>\n168<\/sup><\/a><\/td>\n<\/tr>\n
lower glucose level<\/td>\nhigher glucose level<\/td>\n169<\/sup><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/figure>\n

<\/p>\n

150\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Danesh, V. et al.<\/em> Symptom Clusters Seen in Adult COVID-19 Recovery Clinic Care Seekers. J Gen Intern Med<\/em> 38<\/strong>, 442-449 (2023). https:\/\/doi.org\/10.1007\/s11606-022-07908-4<\/a><\/p>\n

<\/p>\n

151\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Aronoff, D. M. et al.<\/em> E-prostanoid 3 receptor deletion improves pulmonary host defense and protects mice from death in severe Streptococcus pneumoniae infection. J Immunol<\/em> 183<\/strong>, 2642-2649 (2009). https:\/\/doi.org\/10.4049\/jimmunol.0900129<\/a><\/p>\n

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152\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Maher, S. A., Birrell, M. A. & Belvisi, M. G. Prostaglandin E2 mediates cough via the EP3 receptor: implications for future disease therapy. Am J Respir Crit Care Med<\/em> 180<\/strong>, 923-928 (2009). https:\/\/doi.org\/10.1164\/rccm.200903-0388OC<\/a><\/p>\n

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153\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Kervevan, J. et al.<\/em> Divergent adaptive immune responses define two types of long COVID. Frontiers in Immunology<\/em> 14<\/strong> (2023). https:\/\/doi.org\/10.3389\/fimmu.2023.1221961<\/a><\/p>\n

<\/p>\n

154\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Okano, M. et al.<\/em> E prostanoid 2 (EP2)\/EP4-mediated suppression of antigen-specific human T-cell responses by prostaglandin E2. Immunology<\/em> 118<\/strong>, 343-352 (2006). https:\/\/doi.org\/10.1111\/j.1365-2567.2006.02376.x<\/a><\/p>\n

<\/p>\n

155\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Muenchhoff, M. & Goulder, P. J. Sex differences in pediatric infectious diseases. J Infect Dis<\/em> 209 Suppl 3<\/strong>, S120-126 (2014). https:\/\/doi.org\/10.1093\/infdis\/jiu232<\/a><\/p>\n

<\/p>\n

156\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Blesson, C. S., B\u00fcttner, E., Masironi, B. & Sahlin, L. Prostaglandin receptors EP and FP are regulated by estradiol and progesterone in the uterus of ovariectomized rats. Reproductive Biology and Endocrinology<\/em> 10<\/strong>, 3 (2012). https:\/\/doi.org\/10.1186\/1477-7827-10-3<\/a><\/p>\n

<\/p>\n

157\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Gross, R. S. et al.<\/em> Characterizing Long COVID in Children and Adolescents. Jama<\/em> 332<\/strong>, 1174-1188 (2024). https:\/\/doi.org\/10.1001\/jama.2024.12747<\/a><\/p>\n

<\/p>\n

158\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Kikkenborg Berg, S. et al.<\/em> Long COVID symptoms in SARS-CoV-2-positive children aged 0-14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study. Lancet Child Adolesc Health<\/em> 6<\/strong>, 614-623 (2022). https:\/\/doi.org\/10.1016\/s2352-4642(22)00154-7<\/a><\/p>\n

<\/p>\n

159\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Queiroz, M. A. F. et al.<\/em> Cytokine Profiles Associated With Acute COVID-19 and Long COVID-19 Syndrome. Front Cell Infect Microbiol<\/em> 12<\/strong>, 922422 (2022). https:\/\/doi.org\/10.3389\/fcimb.2022.922422<\/a><\/p>\n

<\/p>\n

160\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Kaspersen, K. A. et al.<\/em> Symptoms reported by SARS-CoV-2 seropositive and seronegative healthcare and administrative employees in Denmark from May to August 2020. Int J Infect Dis<\/em> 109<\/strong>, 17-23 (2021). https:\/\/doi.org\/10.1016\/j.ijid.2021.06.017<\/a><\/p>\n

<\/p>\n

161\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Glynne, P., Tahmasebi, N., Gant, V. & Gupta, R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med<\/em> 70<\/strong>, 61-67 (2022). https:\/\/doi.org\/10.1136\/jim-2021-002051<\/a><\/p>\n

<\/p>\n

162\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Machado, N. L. S., Bandaru, S. S., Abbott, S. B. G. & Saper, C. B. EP3R-Expressing Glutamatergic Preoptic Neurons Mediate Inflammatory Fever. J Neurosci<\/em> 40<\/strong>, 2573-2588 (2020). https:\/\/doi.org\/10.1523\/JNEUROSCI.2887-19.2020<\/a><\/p>\n

<\/p>\n

163\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Cipollone, F. et al.<\/em> Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human. Arterioscler Thromb Vasc Biol<\/em> 25<\/strong>, 1925-1931 (2005). https:\/\/doi.org\/10.1161\/01.Atv.0000177814.41505.41<\/a><\/p>\n

<\/p>\n

164\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Mawhin, M. A., Tilly, P. & Fabre, J. E. The receptor EP3 to PGE2: A rational target to prevent atherothrombosis without inducing bleeding. Prostaglandins Other Lipid Mediat<\/em> 121<\/strong>, 4-16 (2015). https:\/\/doi.org\/10.1016\/j.prostaglandins.2015.10.001<\/a><\/p>\n

<\/p>\n

165\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Inazumi, T. et al.<\/em> Prostaglandin E(2)-EP4 Axis Promotes Lipolysis and Fibrosis in Adipose Tissue Leading to Ectopic Fat Deposition and Insulin Resistance. Cell Rep<\/em> 33<\/strong>, 108265 (2020). https:\/\/doi.org\/10.1016\/j.celrep.2020.108265<\/a><\/p>\n

<\/p>\n

166\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Inazumi, T. & Sugimoto, Y. Metabolic Regulation in Adipocytes by Prostanoid Receptors. Biological and Pharmaceutical Bulletin<\/em> 45<\/strong>, 992-997 (2022). https:\/\/doi.org\/10.1248\/bpb.b22-00270<\/a><\/p>\n

<\/p>\n

167\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Kimple, M. E. et al.<\/em> Prostaglandin E2 Receptor, EP3, Is Induced in Diabetic Islets and Negatively Regulates Glucose- and Hormone-Stimulated Insulin Secretion. Diabetes<\/em> 62<\/strong>, 1904-1912 (2013). https:\/\/doi.org\/10.2337\/db12-0769<\/a><\/p>\n

<\/p>\n

168\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 Bosma, K. J. et al.<\/em> Pharmacological blockade of the EP3 prostaglandin E(2) receptor in the setting of type 2 diabetes enhances \u03b2-cell proliferation and identity and relieves oxidative damage. Mol Metab<\/em> 54<\/strong>, 101347 (2021). https:\/\/doi.org\/10.1016\/j.molmet.2021.101347<\/a><\/p>\n

<\/p>\n

169\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 P\u00fcschel, G. P., Kirchner, C., Schr\u00f6der, A. & Jungermann, K. Glycogenolytic and antiglycogenolytic prostaglandin E2 actions in rat hepatocytes are mediated via different signalling pathways. Eur J Biochem<\/em> 218<\/strong>, 1083-1089 (1993). https:\/\/doi.org\/10.1111\/j.1432-1033.1993.tb18468.x<\/a><\/p>\n

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Hypothetical biomarkers for two presumed categories of LC patients: \u201cEP3-up\u201d and \u201cEP3-down\u201d The table below lists reported biomedical characteristics of […]<\/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":"default","site-content-layout":"","ast-site-content-layout":"default","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":"","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-1476","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/1476","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=1476"}],"version-history":[{"count":65,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/1476\/revisions"}],"predecessor-version":[{"id":5976,"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=\/wp\/v2\/pages\/1476\/revisions\/5976"}],"wp:attachment":[{"href":"https:\/\/pge2-hypothesis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1476"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}