{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:29:45Z","timestamp":1788953385795,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hirszfeld Institute","award":["501-15"],"award-info":[{"award-number":["501-15"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytomegalovirus (CMV) syndrome and infectious disease are defined as pathogen detection with appropriate clinical symptoms, but there are not pathognomonic signs of CMV disease. Although the prodrome of acute minor viral infections leukopenia (lymphopenia and neutropenia) is noted with onset of fever, followed by monocytosis, the role of monocytosis in CMV disease has not been described. Furthermore, under influence of corticosteroid therapy, CMV reactivation and monocytosis are described, but without a strict relationship with steroids dose. In the study, the monocyte level was investigated during the CMV infectious process. Regrettably, a non-selected group of 160 patients with high CMV viremia showed high dispersion of monocyte level and comparable with the median value for healthy subjects. Therefore, we investigated monocyte level in CMV-infected patients in relation to the logarithmic phase of the infectious process. Samples from patients with active CMV replication (exponential growth of CMV viremia) were tested. Significant monocytosis (above 1200\/\u00b5L) during the logarithmic phase of CMV infection (with exponent between 3.23 and 5.77) was observed. Increased count and percentage of monocytes correlated with viral replication in several clinical situations except when there was a rapid recovery without relapse. Furthermore, glucocorticoids equivalent to 10 and 20 mg of dexamethasone during a 2\u20133-week period caused monocytosis\u2014significant increase (to 1604 and 2214\/\u00b5L, respectively). Conclusion: In light of the logarithmic increase of viral load, high monocytosis is a hallmark of CMV replication. In the COVID-19 era, presence of high virus level, especially part of virome (CMV) in the molecular technique, is not sufficient for the definition of either proven or probable CMV replication at any site. These preliminary observations merit additional studies to establish whether this clinical response is mediated by monocyte production or by decrease of differentiation to macrophages.<\/jats:p>","DOI":"10.3390\/ijms23179595","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T21:03:51Z","timestamp":1661375031000},"page":"9595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["High Monocyte Count Associated with Human Cytomegalovirus Replication In Vivo and Glucocorticoid Therapy May Be a Hallmark of Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5692-4734","authenticated-orcid":false,"given":"Przemyslaw","family":"Zdziarski","sequence":"first","affiliation":[{"name":"Lower Silesian Oncology, Pulmonology and Hematology Center, P.O. Box 1818, 50-385 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-6591","authenticated-orcid":false,"given":"Andrzej","family":"Gamian","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s40168-020-00875-0","article-title":"Microbiome definition re-visited: Old concepts and new challenges","volume":"8","author":"Berg","year":"2020","journal-title":"Microbiome"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/cid\/ciw668","article-title":"Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials","volume":"64","author":"Ljungman","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1\u221216","DOI":"10.1007\/s40121-017-0180-z","article-title":"Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation","volume":"7","author":"Styczynski","year":"2018","journal-title":"Infect. Dis. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"277\u2212284","DOI":"10.1111\/imj.14462","article-title":"New advances in the management of cytomegalovirus in allogeneic haemopoietic stem cell transplantation","volume":"50","author":"Yong","year":"2020","journal-title":"Intern. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nguyen, C.C., and Kamil, J.P. (2018). Pathogen at the Gates: Human Cytomegalovirus Entry and Cell Tropism. Viruses, 10.","DOI":"10.20944\/preprints201811.0378.v2"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124\u2212134","DOI":"10.1097\/00005792-198603000-00005","article-title":"Clinical and laboratory evaluation of cytomegalovirus-induced mononucleosis in previously healthy individuals. Report of 82 cases","volume":"65","author":"Horwitz","year":"1986","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"261\u2212265","DOI":"10.3345\/kjp.2017.60.8.261","article-title":"Characteristics and prognosis of hepatic cytomegalovirus infection in children: 10 years of experience at a university hospital in Korea","volume":"60","author":"Min","year":"2017","journal-title":"Korean J. Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gugliesi, F., Coscia, A., Griffante, G., Galitska, G., Pasquero, S., Albano, C., and Biolatti, M. (2020). Where do we Stand after Decades of Studying Human Cytomegalovirus?. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050685"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4806\u22124812","DOI":"10.1128\/JVI.73.6.4806-4812.1999","article-title":"Quantitative analysis of latent human cytomegalovirus","volume":"73","author":"Slobedman","year":"1999","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/clinids\/24.1.52","article-title":"Severe cytomegalovirus infection in immunocompetent patients","volume":"24","author":"Eddleston","year":"1997","journal-title":"Clin. Infect Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s15010-003-7503-6","article-title":"Primary CMV infections an important differential diagnosis in outpatients","volume":"31","author":"Ruef","year":"2003","journal-title":"Infection"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Park, K.H., Ryu, J.H., Bae, H., Yun, S., Jang, J.H., Han, K., Cho, B.S., Kim, H.-J., Lee, H., and Oh, E.-J. (2020). Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103663"},{"key":"ref_13","unstructured":"Apperley, J., Carreras, E., Gluckman, E., and Masszi, T. (2012). Viral Infections. ESH-EBMT Handbook on Haemopoietic Stem Cell Transplantation, Springer."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zdziarski, P. (2019). CMV-Specific Immune Response-New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020271"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1296\u22121305","DOI":"10.1016\/j.bbmt.2009.06.008","article-title":"Interferon gamma 13-CA-repeat homozygous genotype and a low proportion of CD4(+) lymphocytes are independent risk factors for cytomegalovirus reactivation with a high number of copies in hematopoietic stem cell transplantation recipients","volume":"15","author":"Jaskula","year":"2009","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1128\/jvi.68.3.1597-1604.1994","article-title":"Induction of endogenous human cytomegalovirus gene expression after differentiation of monocytes from healthy carriers","volume":"68","author":"Sissons","year":"1994","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3389\/fcimb.2020.00368","article-title":"The Differentiation of Human Cytomegalovirus Infected-Monocytes Is Required for Viral Replication","volume":"10","author":"Min","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"11879\u221211883","DOI":"10.1073\/pnas.91.25.11879","article-title":"Human cytomegalovirus latent infection of granulocyte-macrophage progenitors","volume":"91","author":"Kondo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1182\/blood-2009-02-203307","article-title":"Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients","volume":"113","author":"Zhou","year":"2009","journal-title":"Blood"},{"key":"ref_20","unstructured":"Williamson, M.A., and Snyder, M.L. (2015). Hematologic Disorders. Wallach\u2019s Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis, Wolters Kluwer Philadelphia. [10th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.3390\/v7031391","article-title":"Anti-CMV-IgG positivity of donors is beneficial for alloHSCT recipients with respect to the better short-term immunological recovery and high level of CD4+CD25 high lymphocytes","volume":"7","author":"Jaskula","year":"2015","journal-title":"Viruses"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1878\u22121886","DOI":"10.1038\/sj.leu.2400847","article-title":"Flow cytometry CD45 gating for immunophenotyping of acute myeloid leukemia","volume":"11","author":"Lacombe","year":"1997","journal-title":"Leukemia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fcvm.2017.00012","article-title":"Changes in Circulating Monocyte Subsets (CD16 Expression) and Neutrophil-to-Lymphocyte Ratio Observed in Patients Undergoing Cardiac Surgery","volume":"4","author":"Gawdat","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_24","first-page":"135\u2212139","article-title":"Monocyte subsets in man and other species","volume":"289","year":"2014","journal-title":"Cell. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1159\/000163628","article-title":"Differentiation of human monocytes into CD14 negative accessory cells: Do dendritic cells derive from the monocytic lineage?","volume":"59","author":"Peters","year":"1991","journal-title":"Pathobiology"},{"key":"ref_26","first-page":"721\u2212728","article-title":"Quantitation of surface CD14 on human monocytes and neutrophils","volume":"61","author":"Strijp","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"ref_27","unstructured":"(2007). Reference Leukocyte (WBC) Differential Count (Proportional) and Evaluation of Instrument Methods. Standard No. H20-A2."},{"key":"ref_28","first-page":"973\u2212982","article-title":"Toward a reference method for leukocyte differential counts in blood: Comparison of three flow cytometric candidate methods","volume":"81","author":"Roussel","year":"2012","journal-title":"Cytom. Part A"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s40348-019-0092-y","article-title":"Functional analysis of granulocyte and monocyte subpopulations in neonates","volume":"6","author":"Hegge","year":"2019","journal-title":"Mol. Cell. Pediatrics"},{"key":"ref_30","first-page":"198\u2212201","article-title":"Value of antiviral therapy for infectious monocytosis in children","volume":"14","author":"Zhu","year":"2012","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"14\u221223","DOI":"10.1532\/LH96.03030","article-title":"Application of receiver operating characteristics curve (ROC) analysis when definitive and suspect morphologic flags appear in the new Coulter LH 750 analyzer","volume":"10","author":"Aulesa","year":"2004","journal-title":"Lab. Hematol."},{"key":"ref_32","first-page":"423","article-title":"Blood Monocytes and Their Subsets: Established Features and Open Questions","volume":"6","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"91\u221297","DOI":"10.1111\/j.1365-2257.2005.00676.x","article-title":"Evaluation of the monocyte counting by two automated haematology analysers compared with flow cytometry","volume":"27","author":"Grimaldi","year":"2005","journal-title":"Clin. Lab. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"641\u2212650","DOI":"10.1309\/AJCP7D8ECZRXGWCG","article-title":"Comparison of automated differential blood cell counts from Abbott Sapphire, Siemens Advia 120, Beckman Coulter DxH 800, and Sysmex XE\u22122100 in normal and pathologic samples","volume":"139","author":"Meintker","year":"2013","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1099\/0022-1317-72-9-2059","article-title":"Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells","volume":"72","author":"Sissons","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1182\/blood-2017-03-771261","article-title":"Circulatory and maturation kinetics of human monocyte subsets in vivo","volume":"130","author":"Tak","year":"2017","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00430-019-00592-y","article-title":"Cellular reservoirs of latent cytomegaloviruses","volume":"208","author":"Reddehase","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e22374","DOI":"10.1002\/jcla.22374","article-title":"Correlation between the cell population in the automated hematology analyzer high-fluorescence region and atypical lymphocyte flags","volume":"32","author":"Xie","year":"2018","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_39","first-page":"45","article-title":"Morphometric analysis of lymphocyte stimulation Morfometryczna analiza stymulacji limfocyt\u00f3w-doniesienie wst\u0119pne Diag","volume":"39","author":"Zdziarski","year":"2003","journal-title":"Lab"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2101\u22122109","DOI":"10.1002\/jmv.23713","article-title":"Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome","volume":"85","author":"Montoya","year":"2013","journal-title":"J. Med. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S78","DOI":"10.1111\/j.1600-6143.2009.02897.x","article-title":"AST Infectious Diseases Community of Practice. Cytomegalovirus in solid organ transplant recipients","volume":"9","author":"Humar","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/bcp.12637","article-title":"Inhaled corticosteroids: Potency, dose equivalence and therapeutic index","volume":"80","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"31\u221239","DOI":"10.1016\/j.plefa.2018.11.004","article-title":"Antiemetic doses of dexamethasone and their effects on immune cell populations and plasma mediators of inflammation resolution in healthy volunteers","volume":"139","author":"Barden","year":"2018","journal-title":"Prostaglandins Leukot Essent Fat. Acids"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12985-021-01674-1","article-title":"Modulation of host cell signaling during cytomegalovirus latency and reactivation","volume":"18","author":"Smith","year":"2021","journal-title":"Virol. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/rmv.659","article-title":"Cytomegalovirus seroconversion rates and risk factors: Implications for congenital CMV","volume":"20","author":"Hyde","year":"2010","journal-title":"Rev. Med. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e7031","DOI":"10.1097\/MD.0000000000007031","article-title":"A case report of lymphoid intestitial pneumonia in common variable immunodeficiency: Oligoclonal expansion of effector lymphocytes with preferential cytomegalovirus-specific immune response and lymphoproliferative disease promotion","volume":"96","author":"Zdziarski","year":"2017","journal-title":"Medicine"},{"key":"ref_47","first-page":"78\u221285","article-title":"Importance of the Tumor Boards\u2019 decisions for the patientcentered care\u2014Case studies in the COVID-19 era","volume":"50","author":"Zdziarski","year":"2020","journal-title":"Pol. Merkur. Lek."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/cdli.2.3.337-342.1995","article-title":"Comparison of the effects of Ficoll-Hypaque separation and whole blood lysis on results of immunophenotypic analysis of blood and bone marrow samples from patients with hematologic malignancies","volume":"2","author":"Tamul","year":"1995","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/(SICI)1097-0320(19970415)30:2<72::AID-CYTO2>3.0.CO;2-F","article-title":"Toward a new reference method for the leukocyte five-part differential","volume":"30","author":"Hubl","year":"1997","journal-title":"Cytometry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"489\u2212494","DOI":"10.1016\/j.amjhyper.2004.01.010","article-title":"Glucocorticoid sensitivity of circulating monocytes in essential hypertension","volume":"17","author":"Wirtz","year":"2004","journal-title":"Am. J. Hypertens."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e133960","DOI":"10.1172\/JCI133960","article-title":"CMV viral load kinetics as surrogate endpoints after allogeneic transplantation","volume":"131","author":"Duke","year":"2021","journal-title":"J. Clin. Investig."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:14:39Z","timestamp":1760141679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":51,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms23179595"],"URL":"https:\/\/doi.org\/10.3390\/ijms23179595","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,24]]}}}