{"doi":"10.1101/2023.06.23.23291827","title":"Increased circulating fibronectin, depletion of natural IgM and heightened EBV, HSV-1 reactivation in ME/CFS and long COVID","abstract":"Myalgic Encephalomyelitis/ Chronic Fatigue syndrome (ME/CFS) is a complex, debilitating, long-term illness without a diagnostic biomarker. ME/CFS patients share overlapping symptoms with long COVID patients, an observation which has strengthened the infectious origin hypothesis of ME/CFS. However, the exact sequence of events leading to disease development is largely unknown for both clinical conditions. Here we show antibody response to herpesvirus dUTPases, particularly to that of Epstein-Barr virus (EBV) and HSV-1, increased circulating fibronectin (FN1) levels in serum and depletion of natural IgM against fibronectin ((n)IgM-FN1) are common factors for both severe ME/CFS and long COVID. We provide evidence for herpesvirus dUTPases-mediated alterations in host cell cytoskeleton, mitochondrial dysfunction and OXPHOS. Our data show altered active immune complexes, immunoglobulin-mediated mitochondrial fragmentation as well as adaptive IgM production in ME/CFS patients. Our findings provide mechanistic insight into both ME/CFS and long COVID development. Finding of increased circulating FN1 and depletion of (n)IgM-FN1 as a biomarker for the severity of both ME/CFS and long COVID has an immediate implication in diagnostics and development of treatment modalities.","journal":"medRxiv","year":2023,"id":389828,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1160430,"name":"Claudia Hollmann","orcid":"0000-0002-3933-8370","position":1,"is_corresponding":false},{"id":1161033,"name":"Sharada Kalanidhi","orcid":null,"position":2,"is_corresponding":false},{"id":1161034,"name":"Arnhild Grothey","orcid":null,"position":3,"is_corresponding":false},{"id":1160431,"name":"Samuel Keating","orcid":"0000-0003-1038-2498","position":4,"is_corresponding":false},{"id":870419,"name":"Irene Mena-Palomo","orcid":"0000-0003-1200-1599","position":5,"is_corresponding":false},{"id":1161035,"name":"Stephanie Lamer","orcid":null,"position":6,"is_corresponding":false},{"id":486921,"name":"Andreas Schlösser","orcid":"0000-0003-0612-9932","position":7,"is_corresponding":false},{"id":1161036,"name":"Agnes Kaiping","orcid":null,"position":8,"is_corresponding":false},{"id":1160432,"name":"Carsten Scheller","orcid":"0000-0002-0367-1905","position":9,"is_corresponding":false},{"id":1161037,"name":"Franzeska Sotzny","orcid":null,"position":10,"is_corresponding":false},{"id":1160433,"name":"Anna Horn","orcid":"0000-0003-0494-6090","position":11,"is_corresponding":false},{"id":1160434,"name":"Carolin Nürnberger","orcid":"0009-0007-1029-3707","position":12,"is_corresponding":false},{"id":1033341,"name":"Vladimir Cejka","orcid":"0000-0003-4393-1772","position":13,"is_corresponding":false},{"id":1161038,"name":"Boshra Afshar","orcid":null,"position":14,"is_corresponding":false},{"id":28394,"name":"Thomas Bahmer","orcid":"0000-0002-7677-7057","position":15,"is_corresponding":false},{"id":14022,"name":"Stefan Schreiber","orcid":"0000-0003-2254-7771","position":16,"is_corresponding":false},{"id":28526,"name":"Jörg Janne Vehreschild","orcid":"0000-0002-5446-7170","position":17,"is_corresponding":false},{"id":1160435,"name":"Olga Miljukov","orcid":"0000-0003-4790-5918","position":18,"is_corresponding":false},{"id":1160436,"name":"Christian Schäfer","orcid":"0000-0001-8873-7231","position":19,"is_corresponding":false},{"id":1161039,"name":"Luzie Kretzler","orcid":null,"position":20,"is_corresponding":false},{"id":281746,"name":"Thomas Keil","orcid":"0000-0002-9108-3360","position":21,"is_corresponding":false},{"id":1160437,"name":"Jens‐Peter Reese","orcid":"0000-0003-3545-2552","position":22,"is_corresponding":false},{"id":1160438,"name":"Felizitas A. Eichner","orcid":"0000-0002-5415-0456","position":23,"is_corresponding":false},{"id":1160439,"name":"Lena Schmidbauer","orcid":"0000-0003-2606-8655","position":24,"is_corresponding":false},{"id":1160440,"name":"Peter U. Heuschmann","orcid":"0000-0002-2681-3515","position":25,"is_corresponding":false},{"id":1160441,"name":"Stefan Störk","orcid":"0000-0002-1771-7249","position":26,"is_corresponding":false},{"id":1160442,"name":"Caroline Morbach","orcid":"0000-0002-0920-6094","position":27,"is_corresponding":false},{"id":681525,"name":"Gabriela Riemekasten","orcid":"0000-0002-5406-2464","position":28,"is_corresponding":false},{"id":1160443,"name":"Niklas Beyersdorf","orcid":"0000-0002-9236-5415","position":29,"is_corresponding":false},{"id":773753,"name":"Carmen Scheibenbogen","orcid":"0000-0002-8554-9638","position":30,"is_corresponding":false},{"id":264428,"name":"Robert K. Naviaux","orcid":"0000-0001-5832-2297","position":31,"is_corresponding":false},{"id":934835,"name":"Marshall V. Williams","orcid":"0000-0003-2356-4725","position":32,"is_corresponding":false},{"id":554419,"name":"Maria E. Ariza","orcid":"0000-0003-2560-5367","position":33,"is_corresponding":false},{"id":278182,"name":"Bhupesh K. Prusty","orcid":"0000-0001-7051-4670","position":34,"is_corresponding":false},{"id":894351,"name":"Zheng Liu","orcid":"0000-0002-4168-6702","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T01:18:27.054415Z","pmid":"37425897","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}