{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:33:29Z","timestamp":1787772809400,"version":"build-2784847793"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"US Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX004434)"],"award-info":[{"award-number":["I01BX004434)"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VA SeqCure Network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Previously healthy adults hospitalized with an acute undifferentiated illness who test positive for cytomegalovirus (CMV) immunoglobulin M (IgM) in their serum may have a primary CMV infection, CMV reactivation\/reinfection, or a false-positive result. We aimed to understand how clinicians interpret and incorporate positive CMV IgM test results into their diagnostic and management decisions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a retrospective case series study of 13 previously healthy, immunocompetent adults hospitalized with an acute illness in a 12-hospital system from 1 January 2017 to 1 January 2020, who tested positive for CMV IgM within 3 days of hospitalization. Twelve of 13 had CMV immunoglobulin G (IgG).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among these 13 adults (median age, 36 years), elevated liver enzymes (100%), fever (85%), hepatosplenomegaly (54%), and headache (38%) were common. Lymphocytosis was observed in 5 patients, reactive lymphocytes in 3, and 1 patient died from hemophagocytic lymphohistiocytosis. Dual positivity for CMV and Epstein-Barr virus (EBV) IgM was frequent, yet only 1 patient was tested for both CMV and EBV DNA in blood or for CMV IgG avidity index, which indicated a primary CMV infection. Of the 6 patients with CMV DNA in blood, 4 received anti-CMV treatment. Uncertainty regarding CMV's role in the illness was common, and final assessments varied even among cases with similar clinical presentations and serologic patterns.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Interpreting positive CMV IgM results in immunocompetent adults hospitalized with acute illness is challenging and ambiguous due to test limitations and confounders. Supplemental CMV IgG avidity testing can help determine whether primary CMV infection caused the illness, thereby refining the diagnosis and potentially influencing clinical decision-making.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofaf144","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T06:57:31Z","timestamp":1741589851000},"source":"Crossref","is-referenced-by-count":5,"title":["Deciphering Positive Cytomegalovirus Immunoglobulin M Test Results in Immunocompetent Adults Hospitalized With Illness Suspicious for Acute Cytomegalovirus Infection: A Multihospital Study"],"prefix":"10.1093","volume":"12","author":[{"given":"Shrestha","family":"Samuel","sequence":"first","affiliation":[{"name":"School of Medicine, Creighton University , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-0830","authenticated-orcid":false,"given":"Samantha","family":"Thomas","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Asleson","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Nguyen","sequence":"additional","affiliation":[{"name":"School of Medicine, Creighton University , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9491-1697","authenticated-orcid":false,"given":"Jeffery L","family":"Meier","sequence":"additional","affiliation":[{"name":"Iowa City Veterans Affairs Health Care System , Iowa City, Iowa ,","place":["USA"]},{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of Iowa Carver College of Medicine , Iowa City, Iowa ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-7830","authenticated-orcid":false,"given":"Rima","family":"El-Herte","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Creighton University School of Medicine and CHI Health , Omaha, Nebraska ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"2025032600593129900_ofaf144-B1","doi-asserted-by":"crossref","first-page":"e13512","DOI":"10.1111\/ctr.13512","article-title":"Cytomegalovirus in solid organ transplant recipients\u2014guidelines of the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Razonable","year":"2019","journal-title":"Clin Transplant"},{"key":"2025032600593129900_ofaf144-B2","first-page":"1857","volume-title":"Mandell, Douglas, and Bennett's principles and practice of infectious diseases","author":"Britt","year":"2019","edition":"9th ed"},{"key":"2025032600593129900_ofaf144-B3","first-page":"1163","volume-title":"Schlossberg's clinical infectious disease","author":"El-Herte","year":"2022","edition":"3rd ed"},{"key":"2025032600593129900_ofaf144-B4","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1128\/9781555819156.ch27","volume-title":"Clinical virology manual","author":"Pancholi","year":"2016","edition":"5th ed"},{"key":"2025032600593129900_ofaf144-B5","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ajog.2020.02.018","article-title":"Cytomegalovirus infection during pregnancy: state of the science","volume":"223","author":"Leruez-Ville","year":"2020","journal-title":"Am J Obstet Gynecol"},{"key":"2025032600593129900_ofaf144-B6","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1086\/379711","article-title":"Cytomegalovirus infection in immunocompetent patients","volume":"37","author":"Wreghitt","year":"2003","journal-title":"Clin Infect Dis"},{"key":"2025032600593129900_ofaf144-B7","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.idcr.2017.10.008","article-title":"Primary cytomegalovirus infection in immunocompetent adults in the United States\u2014a case series","volume":"10","author":"Nolan","year":"2017","journal-title":"IDCases"},{"issue":"Suppl 1","key":"2025032600593129900_ofaf144-B8","doi-asserted-by":"crossref","first-page":"S74","DOI":"10.1093\/infdis\/jiz601","article-title":"Clinical diagnostic testing for human cytomegalovirus infections","volume":"221","author":"Razonable","year":"2020","journal-title":"J Infect Dis"},{"key":"2025032600593129900_ofaf144-B9","doi-asserted-by":"crossref","first-page":"e0031323","DOI":"10.1128\/jcm.00313-23","article-title":"Maternal and congenital human cytomegalovirus infection: laboratory testing for detection and diagnosis","volume":"62","author":"Leber","year":"2024","journal-title":"J Clin Microbiol"},{"key":"2025032600593129900_ofaf144-B10","doi-asserted-by":"crossref","first-page":"e0140723","DOI":"10.1128\/jcm.01407-23","article-title":"Performance of eight commercial immunoassays for the detection of cytomegalovirus-specific IgM antibodies in pregnancy\u2014no test fits all needs","volume":"62","author":"Daiminger","year":"2024","journal-title":"J Clin Microbiol"},{"key":"2025032600593129900_ofaf144-B11","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/j.1600-0463.2010.02682.x","article-title":"Comparison of IgG avidity assays in the confirmation of the diagnosis of cytomegalovirus primary infection","volume":"118","author":"Guisasola","year":"2010","journal-title":"APMIS"},{"key":"2025032600593129900_ofaf144-B12","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1128\/CVI.00487-14","article-title":"Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy","volume":"21","author":"Prince","year":"2014","journal-title":"Clin Vaccine Immunol"},{"key":"2025032600593129900_ofaf144-B13","doi-asserted-by":"crossref","first-page":"104641","DOI":"10.1016\/j.jcv.2020.104641","article-title":"Positive predictive values of CMV-IgM and importance of CMV-IgG avidity testing in detecting primary infection in three different clinical settings. A French retrospective cohort study","volume":"132","author":"Perillaud-Dubois","year":"2020","journal-title":"J Clin Virol"},{"key":"2025032600593129900_ofaf144-B14","doi-asserted-by":"crossref","first-page":"100892","DOI":"10.1016\/j.lanepe.2024.100892","article-title":"Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)","volume":"40","author":"Leruez-Ville","year":"2024","journal-title":"Lancet Reg Health Eur"},{"key":"2025032600593129900_ofaf144-B15","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1128\/CMR.15.4.680-715.2002","article-title":"Diagnosis and management of human cytomegalovirus infection in the mother, fetus, and newborn infant","volume":"15","author":"Revello","year":"2002","journal-title":"Clin Microbiol Rev"},{"key":"2025032600593129900_ofaf144-B16","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.3390\/jcm11175006","article-title":"Pitfalls in the serological evaluation of maternal cytomegalovirus infection as a potential cause of fetal and neonatal involvements: a narrative literature review","volume":"11","author":"Iijima","year":"2022","journal-title":"J Clin Med"},{"key":"2025032600593129900_ofaf144-B17","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.jcv.2014.10.002","article-title":"Cytomegalovirus DNAemia in pregnant women","volume":"61","author":"Revello","year":"2014","journal-title":"J Clin Virol"},{"key":"2025032600593129900_ofaf144-B18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13613-020-00793-2","article-title":"Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation","volume":"11","author":"Papazian","year":"2021","journal-title":"Ann Intensive Care"},{"key":"2025032600593129900_ofaf144-B19","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1093\/infdis\/jiaa697","article-title":"Risk factors for cytomegalovirus reactivation and association with outcomes in critically ill adults with sepsis: a pooled analysis of prospective studies","volume":"223","author":"Imlay","year":"2021","journal-title":"J Infect Dis"},{"key":"2025032600593129900_ofaf144-B20","doi-asserted-by":"crossref","first-page":"698808","DOI":"10.3389\/fimmu.2021.698808","article-title":"Herpes DNAemia and TTV viraemia in intensive care unit critically ill patients: a single-centre prospective longitudinal study","volume":"12","author":"Mallet","year":"2021","journal-title":"Front Immunol"},{"key":"2025032600593129900_ofaf144-B21","doi-asserted-by":"crossref","first-page":"543","DOI":"10.3390\/pathogens12040543","article-title":"Clinical spectrum, radiological findings, and outcomes of severe toxoplasmosis in immunocompetent hosts: a systematic review","volume":"12","author":"Layton","year":"2023","journal-title":"Pathogens"},{"key":"2025032600593129900_ofaf144-B22","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1097\/TP.0000000000002191","article-title":"The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation","volume":"102","author":"Kotton","year":"2018","journal-title":"Transplantation"},{"key":"2025032600593129900_ofaf144-B23"},{"key":"2025032600593129900_ofaf144-B24","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofac316","article-title":"IgM positivity for both EBV and CMV: a clinical conundrum","volume":"9","author":"Jhaveri","year":"2022","journal-title":"Open Forum Infect Dis"},{"issue":"Pt 1","key":"2025032600593129900_ofaf144-B25","first-page":"211","article-title":"Infectious mononucleosis","volume":"390","author":"Dunmire","year":"2015","journal-title":"Curr Top Microbiol Immunol"},{"key":"2025032600593129900_ofaf144-B26","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1128\/CVI.00754-13","article-title":"Performance of the architect EBV antibody panel for determination of Epstein-Barr virus infection stage in immunocompetent adolescents and young adults with clinical suspicion of infectious mononucleosis","volume":"21","author":"Guerrero-Ramos","year":"2014","journal-title":"Clin Vaccine Immunol"},{"key":"2025032600593129900_ofaf144-B27","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1128\/CVI.00372-09","article-title":"Comparison of three automated immunoassay methods for the determination of Epstein-Barr virus\u2013specific immunoglobulin M","volume":"17","author":"Berth","year":"2010","journal-title":"Clin Vaccine Immunol"},{"key":"2025032600593129900_ofaf144-B28","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/(SICI)1096-9071(199811)56:3<186::AID-JMV2>3.0.CO;2-3","article-title":"Immunoreactivation of Epstein-Barr virus due to cytomegalovirus primary infection","volume":"56","author":"Aalto","year":"1998","journal-title":"J Med Virol"},{"key":"2025032600593129900_ofaf144-B29","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1007\/s15010-003-3129-y","article-title":"Primary cytomegalovirus infection in an outpatient setting\u2014laboratory markers and clinical aspects","volume":"31","author":"Just-Nubling","year":"2003","journal-title":"Infection"},{"key":"2025032600593129900_ofaf144-B30","first-page":"7949471","article-title":"Acute cytomegalovirus illness in an immunocompetent adult causing intravascular hemolysis and suspected hemophagocytic lymphohistiocytosis","volume":"2022","author":"Elliott","year":"2022","journal-title":"Case Rep Infect Dis"},{"key":"2025032600593129900_ofaf144-B31","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jneuroim.2006.11.006","article-title":"Primary cytomegalovirus infection in patients with Guillain-Barre syndrome","volume":"183","author":"Steininger","year":"2007","journal-title":"J Neuroimmunol"},{"key":"2025032600593129900_ofaf144-B32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12879-016-1343-3","article-title":"Case report: severe cytomegalovirus primary infection in an immunocompetent adult with disseminated intravascular coagulation treated with valganciclovir","volume":"16","author":"Muller","year":"2016","journal-title":"BMC Infect Dis"},{"key":"2025032600593129900_ofaf144-B33","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1128\/CVI.00697-14","article-title":"Seroprevalence of cytomegalovirus among children 1 to 5 years of age in the United States from the National Health and Nutrition Examination Survey of 2011 to 2012","volume":"22","author":"Lanzieri","year":"2015","journal-title":"Clin Vaccine Immunol"},{"key":"2025032600593129900_ofaf144-B34","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1128\/CVI.05228-11","article-title":"National prevalence estimates for cytomegalovirus IgM and IgG avidity and association between high IgM antibody titer and low IgG avidity","volume":"18","author":"Dollard","year":"2011","journal-title":"Clin Vaccine Immunol"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofaf144\/62357847\/ofaf144.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/12\/3\/ofaf144\/62357847\/ofaf144.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/12\/3\/ofaf144\/62357847\/ofaf144.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T08:42:23Z","timestamp":1743237743000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofaf144\/8066317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,28]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,2,28]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofaf144","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,2,28]]},"article-number":"ofaf144"}}