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Cao Y, Li L. Long-term prognosis following cytomegalovirus respiratory infection in immunocompromised and immunocompetent patients: a retrospective single-centre study. BMC Infect Dis 2025; 25:756. [PMID: 40420006 DOI: 10.1186/s12879-025-11162-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2025] [Accepted: 05/22/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) respiratory infection is associated with a high mortality rate. This observational cohort study investigated the long-term survival of patients after CMV respiratory infection and risk factors affecting their prognosis. METHODS Overall, 569 inpatients with CMV respiratory infection enrolled in this study. The prevalence of comorbidities, clinical characteristics, 30-d, 1-year, and 5-year mortality rates, and prognostic risk factors was analysed. RESULTS The 30-d, 1-year, and 5-year mortality rates of CMV respiratory infection were 21.6%, 51.4%, and 69.2%, respectively. Based on the different underlying diseases, the 1- and 5-year mortality rates were higher in patients with connective tissue diseases (61.7% vs. 79.4%), post-chemoradiotherapy (56.0% vs. 85.0%), interstitial pneumonia or long-term users of glucocorticoids (55.2% vs. 75.7%), and non-immunocompromised patients (53.8% vs. 68.3%). The 30-d mortality rate had the lowest in organ transplant recipients (6.8%), whereas the 5-year mortality rate was the lowest in patients with nephrotic syndrome (38.3%). Additionally, 76% of CMV infections, 85% of Pneumocystis pneumonia infections, and 70% of Aspergillus pneumonia infections occurred within the first 6 months of glucocorticoid or immunosuppressant use. The presence of interstitial pneumonia, respiratory failure, high Pneumonia Severity Index (PSI) and CURB-65 scores, and persistent lymphocytopenia were indicative of a poor 30-d prognosis, while post-organ transplantation was associated with a favourable prognosis. CONCLUSIONS The mortality rate of CMV respiratory infection was found to be high, especially in patients with connective tissue diseases, cancer chemotherapy and radiation therapy, interstitial pneumonia, and non-immunocompromised patients. In patients on long-term immunosuppressants and corticosteroids, particularly within the first 6 months, vigilance needs to be exercised for CMV respiratory infection.
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Affiliation(s)
- Yanting Cao
- Department of Anesthesiology, China-Japan Friendship Hospital, No 2, Yinghua East Road, Chaoyang District, Beijing, 100029, China
| | - Lijuan Li
- Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, No 2, Yinghua East Road, Chaoyang District, Beijing, 100029, China.
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Deinhardt-Emmer S, Chousterman BG, Schefold JC, Flohé SB, Skirecki T, Kox M, Winkler MS, Cossarizza A, Wiersinga WJ, van der Poll T, Weigand MA, Cajander S, Giamarellos-Bourboulis EJ, Lachmann G, Girardis M, Scicluna BP, Ferrer R, Payen D, Weis S, Torres A, Bermejo-Martín JF, Osuchowski MF, Rubio I, Bouma HR. Sepsis in patients who are immunocompromised: diagnostic challenges and future therapies. THE LANCET. RESPIRATORY MEDICINE 2025:S2213-2600(25)00124-9. [PMID: 40409328 DOI: 10.1016/s2213-2600(25)00124-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Revised: 03/31/2025] [Accepted: 04/02/2025] [Indexed: 05/25/2025]
Abstract
Sepsis is a life-threatening, dysregulated host response to infection. Immunosuppression is a risk factor for infections and sepsis. However, the specific immune derangements elevating the risk for infections and sepsis remain unclear in the individual patient, raising the question of whether a general state of immunosuppression exists. In this Review, we explore the relationship between immunosuppression and sepsis, detailing the definitions, causes, and clinical implications. We address the effect of primary immunodeficiencies, acquired conditions, and drugs on the risk of infection and the development of sepsis. Patients with sepsis who are immunocompromised often present with atypical symptoms and diagnostic test results can differ, making early recognition difficult. Future perspectives entail novel biomarkers to improve early sepsis detection and tailored treatments to modulate immune function. Including patients who are immunocompromised in clinical trials is crucial to enhance the relevance of research findings and improve treatment strategies for this vulnerable population.
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Affiliation(s)
- Stefanie Deinhardt-Emmer
- Institute of Medical Microbiology, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
| | - Benjamin G Chousterman
- Department of Anesthesia and Critical Care, Lariboisière Hospital, APHP, Paris, France; Université Paris Cité, Inserm UMRS 942 Mascot, Paris, France
| | - Joerg C Schefold
- Department of Intensive Care Medicine, Inselspital, University of Bern, Bern University Hospital, Bern, Switzerland
| | - Stefanie B Flohé
- Department of Trauma, Hand, and Reconstructive Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
| | - Tomasz Skirecki
- Department of Translational Immunology and Experimental Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Matthijs Kox
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, Netherlands
| | - Martin S Winkler
- Department of Anaesthesiology, University Medical Center Göttingen, Göttingen, Germany
| | - Andrea Cossarizza
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - W Joost Wiersinga
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Department of Medicine, Division of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Tom van der Poll
- Center for Experimental and Molecular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands; Department of Medicine, Division of Infectious Diseases, Amsterdam University Medical Center, Amsterdam, Netherlands; Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Center, Amsterdam, Netherlands
| | - Markus A Weigand
- Department of Anesthesiology, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany
| | - Sara Cajander
- Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Evangelos J Giamarellos-Bourboulis
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece; Hellenic Institute for the Study of Sepsis, Athens, Greece
| | - Gunnar Lachmann
- Department of Anesthesiology and Intensive Care Medicine Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Massimo Girardis
- Department of Anesthesiology and Intensive Care Medicine, University Hospital of Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Brendon P Scicluna
- Department of Applied Biomedical Science, Faculty of Health Sciences, Mater Dei hospital, University of Malta, Malta; Centre for Molecular Medicine and Biobanking, Biomedical Sciences, University of Malta, Malta
| | - Ricard Ferrer
- Department of Intensive Care Medicine, Vall d'Hebron University Hospital, Barcelona, Spain; SODIR, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Didier Payen
- Paris 7 University Denis Diderot, Paris Sorbonne, Cité, Paris, France; Service de Maladies Infectieuses, CHU de Nice, Nice, France
| | - Sebastian Weis
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany; Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany; Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll Institute-HKI, Jena, Germany
| | - Antoni Torres
- Pulmonology Department, Hospital Clinic of Barcelona, University of Barcelona, Ciberes, IDIBAPS, ICREA, Barcelona, Spain
| | - Jesús F Bermejo-Martín
- School of Medicine, Universidad de Salamanca, Salamanca, Spain; Instituto de Investigación Biomédica de Salamanca, Salamanca, Spain; Centro de Investigación Biomédica en Red en Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
| | - Marcin F Osuchowski
- Ludwig Boltzmann Institute for Traumatology, the Research Center in Cooperation with AUVA, Vienna, Austria
| | - Ignacio Rubio
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller University Jena, Jena, Germany
| | - Hjalmar R Bouma
- Department of Acute Care, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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Boquett JA, Sauter J, Schmidt AH, Maiers M, Hollenbach JA. Human leukocyte antigen variation is associated with cytomegalovirus serostatus in healthy individuals. Am J Hum Genet 2025; 112:913-926. [PMID: 40049169 DOI: 10.1016/j.ajhg.2025.02.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 02/05/2025] [Accepted: 02/07/2025] [Indexed: 03/12/2025] Open
Abstract
Cytomegalovirus (CMV) is a common β-herpes virus worldwide with an estimated seroprevalence among the general population of 83%. Primary infection is usually benign; however, CMV can cause severe morbidity in newborns in whom it is acquired congenitally, as well as immunocompromised individuals. Understanding the role of immunogenetic variation in risk for CMV infection can provide insight into the immune control of this ubiquitous pathogen. Here, we evaluated the association of human leukocyte antigen (HLA) genetic variation with CMV seropositivity in more than 518,000 individuals from two independent cohorts. We found three HLA class II alleles (HLA-DRB1∗04:03 with risk; HLA-DRB1∗01:03 and HLA-DRB1∗07:01 with protection) to be significantly associated with CMV serostatus across both cohorts and in multiple population subgroups. Interestingly, HLA-DRB1∗04:03 and HLA-DRB1∗01:03, the alleles with the strongest observed effect, are relatively rare, while common homologous alleles show no association with CMV. We show that these differences are mediated by changes in charge and volume to two key pockets in the peptide-binding groove of the HLA molecule, providing a structural basis for the observed association. Our results provide population-scale evidence for the role of HLA in mediating infection with this ubiquitous human virus and a framework for understanding immunological conditions necessary for efficient viral control.
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Affiliation(s)
- Juliano A Boquett
- Department of Neurology, University of California, San Francisco, San Francisco, CA, USA
| | | | | | - Martin Maiers
- CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN, USA
| | - Jill A Hollenbach
- Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
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Varga P, Biró E, Berkes A, Lakatos E, Szikszay E, Prohászka Z, Szabó T. Use of complement C5-inhibitor eculizumab in patients with infection-associated hemolytic uremic syndrome - a case-series report. BMC Pediatr 2025; 25:181. [PMID: 40065282 PMCID: PMC11895294 DOI: 10.1186/s12887-025-05546-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Hemolytic uremic syndrome (HUS), characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury (AKI), remains a leading cause of pediatric AKI. The complement system has a crucial role in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and eculizumab (ECZ) was approved as standard of care for its treatment. The two widely characterized forms of infection-associated HUS are Shiga toxin-producing E. coli (STEC)-HUS and Streptococcus pneumoniae-associated (SP)-HUS. Extrarenal manifestations such as central nervous system (CNS) involvement occur approximately in 20% of the cases and are accompanied by higher mortality. Abnormalities of the alternative complement pathway may also contribute to the development of both STEC-HUS and SP-HUS, offering a potential treatment option for complement C5 inhibition. Beyond best supportive care as standard therapeutic approach, ECZ has been successfully used in both STEC-HUS and SP-HUS patients. We provide further support that early use of ECZ for infection-associated HUS with severe clinical manifestation and abnormal complement-activation profile may be an effective therapeutic approach. CASE PRESENTATION We report on three children (median age: 2 years, range: 2-10 years) diagnosed with infection-associated HUS treated with complement C5-inhibitor ECZ. All three patients were treated with ECZ and had excellent outcome. We retrospectively analyzed the clinical course, laboratory data and outcome of children with infection-associated HUS treated with ECZ. CONCLUSION In accordance with previous observations ECZ is an efficacious therapeutic choice in severe HUS patients with multiorgan involvement. A detailed complement activation profile, especially sC5b-9, is useful to indicate ECZ administration.
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Affiliation(s)
- Petra Varga
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98, 4028, Debrecen, Hungary
| | - Erika Biró
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98, 4028, Debrecen, Hungary
| | - Andrea Berkes
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98, 4028, Debrecen, Hungary
| | - Erzsébet Lakatos
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98, 4028, Debrecen, Hungary
| | - Edit Szikszay
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98, 4028, Debrecen, Hungary
| | - Zoltán Prohászka
- Department of Internal Medicine and Hematology, Semmelweis University, Szentkirály Str. 46, 1088, Budapest, Hungary
| | - Tamás Szabó
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Nagyerdei Krt 98, 4028, Debrecen, Hungary.
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Ozer EA, Keskin A, Berrak YH, Cankara F, Can F, Gursoy-Ozdemir Y, Keskin O, Gursoy A, Yapici-Eser H. Shared interactions of six neurotropic viruses with 38 human proteins: a computational and literature-based exploration of viral interactions and hijacking of human proteins in neuropsychiatric disorders. DISCOVER MENTAL HEALTH 2025; 5:18. [PMID: 39987419 PMCID: PMC11846830 DOI: 10.1007/s44192-025-00128-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 01/09/2025] [Indexed: 02/24/2025]
Abstract
INTRODUCTION Viral infections may disrupt the structural and functional integrity of the nervous system, leading to acute conditions such as encephalitis, and neuropsychiatric conditions as mood disorders, schizophrenia, and neurodegenerative diseases. Investigating viral interactions of human proteins may reveal mechanisms underlying these effects and offer insights for therapeutic interventions. This study explores molecular interactions of virus and human proteins that may be related to neuropsychiatric disorders. METHODS Herpes Simplex Virus-1 (HSV-1), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Influenza A virus (IAV) (H1N1, H5N1), and Human Immunodeficiency Virus (HIV1&2) were selected as key viruses. Protein structures for each virus were accessed from the Protein Data Bank and analyzed using the HMI-Pred web server to detect interface mimicry between viral and human proteins. The PANTHER classification system was used to categorize viral-human protein interactions based on function and cellular localization. RESULTS Energetically favorable viral-human protein interactions were identified for HSV-1 (467), CMV (514), EBV (495), H1N1 (3331), H5N1 (3533), and HIV 1&2 (62425). Besides immune and apoptosis-related pathways, key neurodegenerative pathways, including those associated with Parkinson's and Huntington's diseases, were frequently interacted. A total of 38 human proteins, including calmodulin 2, Ras-related botulinum toxin substrate 1 (Rac1), PDGF-β, and vimentin, were found to interact with all six viruses. CONCLUSION The study indicates a substantial number of energetically favorable interactions between human proteins and selected viral proteins, underscoring the complexity and breadth of viral strategies to hijack host cellular mechanisms. Further in vivo and in vitro validation is required to understand the implications of these interactions.
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Affiliation(s)
| | - Aleyna Keskin
- School of Medicine, Koç University, Istanbul, Turkey
| | | | - Fatma Cankara
- Graduate School of Sciences and Engineering, Computational Sciences and Engineering, Koç University, Istanbul, Turkey
| | - Fusun Can
- Department of Microbiology, School of Medicine, Koç University, Istanbul, Turkey
| | - Yasemin Gursoy-Ozdemir
- Department of Neurology, School of Medicine, Koç University, Istanbul, Turkey
- Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey
| | - Ozlem Keskin
- Department of Chemical and Biological Engineering, College of Engineering, Koç University, Istanbul, Turkey
| | - Attila Gursoy
- Department of Computer Science and Engineering, College of Engineering, Koç University, Istanbul, Turkey.
| | - Hale Yapici-Eser
- Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Turkey.
- Department of Psychiatry, School of Medicine, Koç University, Istanbul, Turkey.
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Mesland JB, Collienne C, Montiel V, Werion A, Hantson P, Wittebole X, Laterre PF, Gerard L. Cytomegalovirus Blood DNAemia in Patients with Severe SARS-CoV-2 Pneumonia. Infect Dis Rep 2025; 17:8. [PMID: 39997460 PMCID: PMC11855763 DOI: 10.3390/idr17010008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 01/11/2025] [Accepted: 01/22/2025] [Indexed: 02/26/2025] Open
Abstract
INTRODUCTION Cytomegalovirus (CMV) DNAemia has been described in critically ill patients, including patients with severe acute respiratory syndrome-coronavirus2 (SARS-CoV-2) infection. Our objective is to evaluate the prevalence and clinical impact of CMV DNAemia among patients undergoing invasive mechanical ventilation (IMV) for severe SARS-CoV-2 infection and to explore the association between CMV DNAemia levels and clinical outcomes. METHODS In this retrospective monocentric study, we included patients admitted in a tertiary ICU for severe COVID-19 and who required IMV. We aimed to compare clinical and demographic variables between patients with and without CMV DNAemia. Univariate and Cox regression analyses were performed to identify factors associated with CMV DNAemia. RESULTS During the study period, CMV blood DNAemia occurred in 30/135 patients (22%). Patients with CMV blood DNAemia had longer ICU and hospital length of stay, as well as longer duration of IMV, and were more likely to have received dexamethasone. However, there was no significant difference in ICU mortality between patients with and without CMV DNAemia (64.8% vs. 56.7%, p = 0.42). The Cox regression analysis showed that dexamethasone was the only factor independently associated with CMV blood DNAemia (HR 4.23 [1.006-17.792], p = 0.049). CONCLUSIONS In patients with severe SARS-CoV-2 pneumonia requiring IMV, CMV DNAemia is common and associated with prolonged ventilation and increased LOS but not with increased mortality.
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Affiliation(s)
- Jean-Baptiste Mesland
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
| | - Christine Collienne
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
| | - Virginie Montiel
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
| | - Alexis Werion
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
| | - Philippe Hantson
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
| | - Xavier Wittebole
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
| | | | - Ludovic Gerard
- Critical Care Department, Cliniques Universitaires Saint-Luc, Université Catolique de Louvain, 1200 Brussels, Belgium
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Maessen L, Boers LS, Heylen J, van Someren Gréve F, Wauters J, Bos LDJ, Feys S. Viral reactivations and fungal infections in nonresolving acute respiratory distress syndrome. Eur Respir Rev 2025; 34:240153. [PMID: 39971398 PMCID: PMC11836671 DOI: 10.1183/16000617.0153-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/21/2024] [Indexed: 02/21/2025] Open
Abstract
Acute respiratory distress syndrome (ARDS) is a condition affecting 10% of patients requiring admission to the intensive care unit and results from endothelial dysfunction, alveolar epithelial injury and unbalanced inflammation, leading to exudative pulmonary oedema. A significant portion of these patients experience a lung injury that fails to resolve. Persistent or worsening respiratory failure beyond 5 days after the initiation of mechanical ventilation is referred to as nonresolving ARDS. Viral and fungal pathogens can exploit the hyperinflammatory environment and altered immune landscape in ARDS, perpetuating a cycle of ongoing inflammation and lung injury, thereby contributing to the progression towards and persistence of nonresolving ARDS, even in previously immunocompetent patients. This review discusses the significance, pathophysiology, diagnostic challenges and key knowledge gaps concerning various viral and fungal pathogens in nonresolving ARDS, with a particular focus on influenza-associated and COVID-19-associated pulmonary aspergillosis and pulmonary reactivation of Herpesviridae, such as cytomegalovirus and herpes simplex virus. Diagnosing these infections is challenging due to their nonspecific clinical presentation and the inability of current tests to distinguish between fungal colonisation or asymptomatic viral shedding and clinically significant infections or reactivations. A deeper understanding of the complex interplay between these pathogens and the host immune system in the context of ARDS, combined with advances in diagnostic and therapeutic strategies, has the potential to enhance the management and prognosis of patients with nonresolving ARDS.
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Affiliation(s)
- Lenn Maessen
- Medical Intensive Care Unit, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Shared first authors
| | - Leonoor S Boers
- Department of Intensive Care Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Shared first authors
| | - Jannes Heylen
- Medical Intensive Care Unit, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - Frank van Someren Gréve
- Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Joost Wauters
- Medical Intensive Care Unit, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Shared last authors
| | - Lieuwe D J Bos
- Department of Intensive Care Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Shared last authors
| | - Simon Feys
- Medical Intensive Care Unit, Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Shared last authors
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Fernández S, Castro P, Azoulay E. What intensivists need to know about cytomegalovirus infection in immunocompromised ICU patients. Intensive Care Med 2025; 51:39-61. [PMID: 39774866 DOI: 10.1007/s00134-024-07737-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Accepted: 11/19/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE Advances in therapeutic care are leading to an increase in the number of patients living with overt immunosuppression. These patients are at risk of cytomegalovirus (CMV) infection and disease that can lead to or develop during ICU admission. This manuscript aims to describe the clinical presentation, risk factors, and management of CMV infection and disease in this patient population. METHODS We conducted a literature search in PubMed up to April 2024, focusing on CMV infection and disease in patients with overt immunosuppression (hematopoietic stem cell and solid organ transplantation, solid or hematologic malignancies, HIV infection, immunosuppressive drugs, including corticosteroids, and primary immunodeficiencies) admitted to the intensive care unit (ICU). As there is limited ICU-specific data on CMV in immunosuppressed patients, many of the findings were extrapolated from the general literature. RESULTS CMV infection and disease in immunocompromised critically ill patients is associated with increased mortality and presents significant management challenges. Clinical manifestations are diverse, shaped by the underlying immune deficiency and primary disease. Pneumonia and encephalitis are among the most severe CMV end-organ diseases. CMV infection may also increase the risk of secondary infections and induce life-threatening conditions, such as thrombotic microangiopathy. Importantly, CMV reactivation is not synonymous with CMV disease, and qPCR testing of body fluids cannot reliably differentiate between viral shedding and tissue-invasive infection, which requires histopathological confirmation. Ganciclovir is commonly the first-line anti-viral, though maribavir shows potential for patients unresponsive to other antivirals. Identifying patients who require prophylactic or preemptive antiviral therapy is essential. CONCLUSIONS CMV infection and disease in critically ill immunocompromised patients pose a unique challenge for intensivists. The broad spectrum of clinical presentations and the difficulty in distinguishing CMV-related symptoms from other causes require a high level of clinical suspicion. Accurate interpretation of nucleic acid load levels and careful evaluation of CMV's pathogenic role when it is found are critical. Further studies focusing specifically on CMV infection and disease in critically ill immunocompromised patients are needed to optimize management strategies.
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Affiliation(s)
- Sara Fernández
- Medical Intensive Care Unit, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain.
- Medical Intensive Care Unit, AP-HP, Saint-Louis University Hospital, Paris, France.
| | - Pedro Castro
- Medical Intensive Care Unit, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Elie Azoulay
- Medical Intensive Care Unit, AP-HP, Saint-Louis University Hospital, Paris, France
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Schattner A. The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review. Pathogens 2024; 13:667. [PMID: 39204267 PMCID: PMC11357360 DOI: 10.3390/pathogens13080667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Revised: 07/09/2024] [Accepted: 07/26/2024] [Indexed: 09/03/2024] Open
Abstract
CMV is a ubiquitous DNA virus that establishes infection and results in 40-100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one.
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Affiliation(s)
- Ami Schattner
- The Faculty of Medicine, Hebrew University Hadassah Medical School, Ein Kerem, Jerusalem 91120, Israel
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10
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Baber A, Calvet L, Vissac C, Salmona M, Legoff J, De Jong A, Mariotte E, Zafrani L, Azoulay E, Darmon M. Cytomegalovirus infection in intensive care unit patients with hematological malignancies: Characteristics and clinical outcomes. J Crit Care 2024; 82:154766. [PMID: 38479298 DOI: 10.1016/j.jcrc.2024.154766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/27/2024] [Accepted: 02/27/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is associated with poor outcome in ICU patients. However, data on immunocompromised patients are scarce. This study aims to describe characteristics and outcomes of critically ill hematological patients and CMV infection. CMV disease characteristics and relationship between CMV viral load, CMV disease, coinfections by other pathogens and outcomes are described. METHODS Retrospective single center study (Jan 2010-Dec 2017). Adult patients, admitted to the ICU, having underlying hematological malignancy and CMV infection were included. Results are reported as median (interquartile) or n (%). Factors associated with hospital mortality or CMV disease were analysed using logistic regression. RESULTS 178 patients were included (median age 55y [42-64], 69.1% male). Hospital mortality was 53% (n = 95). Median viral load was 2.7 Log [2.3-3.5]. CMV disease occurred in 44 (24.7%) patients. Coinfections concerned 159 patients (89.3%). After adjustment for confounders, need for vasopressors (OR 2.53; 95%CI 1.11-5.97) and viral load (OR 1.88 per Log; 95%CI 1.29-2.85) were associated with hospital mortality. However, neither CMV disease nor treatment were associated with outcomes. Allogeneic stem cell transplantation (OR 2.55; 95%CI 1.05-6.16), mechanical ventilation (OR 4.11; OR 1.77-10.54) and viral load (OR 1.77 per Log; 95%CI 1.23-2.61) were independently associated with CMV disease. Coinfections were not associated with CMV disease or hospital mortality. CONCLUSION In critically-ill hematological patients, CMV viral load is independently associated with hospital mortality. Conversely, neither CMV disease nor treatment was associated with outcome suggesting viral load to be a surrogate for immune status rather than a cause of poor outcome.
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Affiliation(s)
- A Baber
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - L Calvet
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - C Vissac
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - M Salmona
- Université de Paris; Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Department of microbiology, Paris, France
| | - J Legoff
- Université de Paris; Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Department of microbiology, Paris, France
| | - A De Jong
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - E Mariotte
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - L Zafrani
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - E Azoulay
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France
| | - M Darmon
- Université de Paris, Assistance Publique-Hôpitaux de Paris; Hôpitaux universitaires Saint-Louis, Lariboisière, Fernand-Widal; Intensive care unit, Paris, France.
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11
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Boers LS, van Someren Gréve F, van Hattem JM, de Brabander J, Zwaan T, van Willigen H, Cornelissen M, de Jong M, van der Poll T, Duitman J, Schinkel J, Bos LDJ. Pulmonary herpes simplex virus and cytomegalovirus in patients with acute respiratory distress syndrome related to COVID-19. Intensive Care Med 2024; 50:1251-1264. [PMID: 39017695 PMCID: PMC11306713 DOI: 10.1007/s00134-024-07529-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 06/14/2024] [Indexed: 07/18/2024]
Abstract
PURPOSE Human herpesviruses, particularly cytomegalovirus (CMV) and herpes simplex virus (HSV), frequently reactivate in critically ill patients, including those with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). The clinical interpretation of pulmonary herpesvirus reactivation is challenging and there is ongoing debate about its association with mortality and benefit of antiviral medication. We aimed to quantify the incidence and pathogenicity of pulmonary CMV and HSV reactivations in critically ill COVID-19 patients. METHODS Mechanically ventilated COVID-19 patients seropositive for CMV or HSV were included in this observational cohort study. Diagnostic bronchoscopy with bronchoalveolar lavage was performed routinely and analyzed for alveolar viral loads and inflammatory biomarkers. Utilizing joint modeling, we explored the dynamic association between viral load trajectories over time and mortality. We explored alveolar inflammatory biomarker dynamics between reactivated and non-reactivated patients. RESULTS Pulmonary reactivation (> 104 copies/ml) of CMV occurred in 6% of CMV-seropositive patients (9/156), and pulmonary reactivation of HSV in 37% of HSV-seropositive patients (63/172). HSV viral load dynamics prior to or without antiviral treatment were associated with increased 90-day mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.04-1.47). The alveolar concentration of several inflammatory biomarkers increased with HSV reactivation, including interleukin (IL)-6, IL-1β, granulocyte colony stimulating factor (G-CSF), and tumor necrosis factor (TNF). CONCLUSION In mechanically ventilated COVID-19 patients, HSV reactivations are common, while CMV reactivations were rare. HSV viral load dynamics prior to or without antiviral treatment are associated with mortality. Alveolar inflammation is elevated after HSV reactivation.
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Affiliation(s)
- Leonoor S Boers
- Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Room G3-228, 1105 AZ, Amsterdam, The Netherlands.
| | - Frank van Someren Gréve
- Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Jarne M van Hattem
- Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Justin de Brabander
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Tom Zwaan
- Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Room G3-228, 1105 AZ, Amsterdam, The Netherlands
| | - Hugo van Willigen
- Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Marion Cornelissen
- Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Menno de Jong
- Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Tom van der Poll
- Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Infection and Immunity, Inflammatory Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - JanWillem Duitman
- Infection and Immunity, Inflammatory Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Pulmonary Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
- Experimental Immunology (EXIM), Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Janke Schinkel
- Medical Microbiology, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Amsterdam, The Netherlands
| | - Lieuwe D J Bos
- Intensive Care Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, Room G3-228, 1105 AZ, Amsterdam, The Netherlands
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12
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Kobayashi R, Hashida N. Overview of Cytomegalovirus Ocular Diseases: Retinitis, Corneal Endotheliitis, and Iridocyclitis. Viruses 2024; 16:1110. [PMID: 39066272 PMCID: PMC11281654 DOI: 10.3390/v16071110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/24/2024] [Accepted: 06/29/2024] [Indexed: 07/28/2024] Open
Abstract
Cytomegalovirus (CMV) infection is a significant clinical concern in newborns, immunocompromised patients with acquired immunodeficiency syndrome (AIDS), and patients undergoing immunosuppressive therapy or chemotherapy. CMV infection affects many organs, such as the lungs, digestive organs, the central nerve system, and eyes. In addition, CMV infection sometimes occurs in immunocompetent individuals. CMV ocular diseases includes retinitis, corneal endotheliitis, and iridocyclitis. CMV retinitis often develops in infected newborns and immunocompromised patients. CMV corneal endotheliitis and iridocyclitis sometimes develop in immunocompetent individuals. Systemic infections and CMV ocular diseases often require systemic treatment in addition to topical treatment.
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Affiliation(s)
| | - Noriyasu Hashida
- Department of Ophthalmology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
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13
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Tassaneeyasin T, Sungkanuparph S, Srichatrapimuk S, Charoensri A, Thammavaranucupt K, Jayanama K, Kirdlarp S. Prevalence and risk factors of cytomegalovirus reactivation in critically Ill patients with COVID-19 pneumonia. PLoS One 2024; 19:e0303995. [PMID: 38771836 PMCID: PMC11108163 DOI: 10.1371/journal.pone.0303995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 05/04/2024] [Indexed: 05/23/2024] Open
Abstract
BACKGROUNDS In critically ill patients with COVID-19, secondary infections are potentially life-threatening complications. This study aimed to determine the prevalence, clinical characteristics, and risk factors of CMV reactivation among critically ill immunocompetent patients with COVID-19 pneumonia. METHODS A retrospective cohort study was conducted among adult patients who were admitted to ICU and screened for quantitative real-time PCR for CMV viral load in a tertiary-care hospital during the third wave of the COVID-19 outbreak in Thailand. Cox regression models were used to identify significant risk factors for developing CMV reactivation. RESULTS A total of 185 patients were studied; 133 patients (71.9%) in the non-CMV group and 52 patients (28.1%) in the CMV group. Of all, the mean age was 64.7±13.3 years and 101 patients (54.6%) were males. The CMV group had received a significantly higher median cumulative dose of corticosteroids than the non-CMV group (301 vs 177 mg of dexamethasone, p<0.001). Other modalities of treatments for COVID-19 including anti-viral drugs, anti-cytokine drugs and hemoperfusion were not different between the two groups (p>0.05). The 90-day mortality rate for all patients was 29.1%, with a significant difference between the CMV group and the non-CMV group (42.3% vs. 24.1%, p = 0.014). Median length of stay was longer in the CMV group than non-CMV group (43 vs 24 days, p<0.001). The CMV group has detectable CMV DNA load with a median [IQR] of 4,977 [1,365-14,742] IU/mL and 24,570 [3,703-106,642] in plasma and bronchoalveolar fluid, respectively. In multivariate analysis, only a cumulative corticosteroids dose of dexamethasone ≥250 mg (HR = 2.042; 95%CI, 1.130-3.688; p = 0.018) was associated with developing CMV reactivation. CONCLUSION In critically ill COVID-19 patients, CMV reactivation is frequent and a high cumulative corticosteroids dose is a significant risk factor for CMV reactivation, which is associated with poor outcomes. Further prospective studies are warranted to determine optimal management.
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Affiliation(s)
- Tanapat Tassaneeyasin
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Somnuek Sungkanuparph
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Sirawat Srichatrapimuk
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Attawit Charoensri
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Kanin Thammavaranucupt
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Kulapong Jayanama
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
| | - Suppachok Kirdlarp
- Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, Thailand
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14
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Ziehe D, Wolf A, Rahmel T, Nowak H, Haberl H, Bergmann L, Rump K, Dyck B, Palmowski L, Marko B, Witowski A, Willemsen KM, Pfaender S, Eisenacher M, Anft M, Babel N, Bracht T, Sitek B, Bayer M, Zarbock A, von Groote T, Putensen C, Ehrentraut SF, Weisheit C, Adamzik M, Unterberg M, Koos B. Exploring the relationship between HCMV serostatus and outcomes in COVID-19 sepsis. Front Immunol 2024; 15:1386586. [PMID: 38779663 PMCID: PMC11109369 DOI: 10.3389/fimmu.2024.1386586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Accepted: 04/23/2024] [Indexed: 05/25/2024] Open
Abstract
Background Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19. Methods A multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis. Results The prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival. Discussion These findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management. Conclusion This study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.
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Affiliation(s)
- Dominik Ziehe
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Alexander Wolf
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Tim Rahmel
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Hartmuth Nowak
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Helge Haberl
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Lars Bergmann
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Katharina Rump
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Birte Dyck
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Lars Palmowski
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Britta Marko
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Andrea Witowski
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Katrin Maria Willemsen
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Stephanie Pfaender
- Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany
| | - Martin Eisenacher
- Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany
- Medical Proteome Analysis, Center for Proteindiagnostics (PRODI), Ruhr University Bochum, Bochum, Germany
| | - Moritz Anft
- Center for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
| | - Nina Babel
- Center for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
| | - Thilo Bracht
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
- Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany
| | - Barbara Sitek
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
- Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany
| | - Malte Bayer
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
- Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany
| | - Alexander Zarbock
- Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie, Universitätsklinikum Münster, Münster, Germany
| | - Thilo von Groote
- Klinik für Anästhesiologie, Operative Intensivmedizin und Schmerztherapie, Universitätsklinikum Münster, Münster, Germany
| | - Christian Putensen
- Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, Bonn, Germany
| | - Stefan Felix Ehrentraut
- Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, Bonn, Germany
| | - Christina Weisheit
- Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, Bonn, Germany
| | - Michael Adamzik
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Matthias Unterberg
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
| | - Björn Koos
- Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany
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15
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Bhide M, Singh O, Nasa P, Juneja D. Cytomegalovirus infection in non-immunocompromised critically ill patients: A management perspective. World J Virol 2024; 13:89135. [PMID: 38616856 PMCID: PMC11008403 DOI: 10.5501/wjv.v13.i1.89135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 12/18/2023] [Accepted: 12/26/2023] [Indexed: 03/11/2024] Open
Abstract
Critically ill patients are a vulnerable group at high risk of developing secondary infections. High disease severity, prolonged intensive care unit (ICU) stay, sepsis, and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections, including cytomegalovirus (CMV). CMV seroconversion has been reported in up to 33% of ICU patients, but its impact on patient outcomes remains a matter of debate. Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/ acquired immuno deficiency syndrome, the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous. Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement. Hence, a better understanding of the symptomatology, diagnostics, and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.
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Affiliation(s)
- Madhura Bhide
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Omender Singh
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
| | - Prashant Nasa
- Department of Critical Care Medicine, NMC Specialty Hospital, Dubai 7832, United Arab Emirates
| | - Deven Juneja
- Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
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16
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Yeh PJ, Wu RC, Chen CL, Chiu CT, Lai MW, Chen CC, Chiu CH, Pan YB, Lin WR, Le PH. Cytomegalovirus Diseases of the Gastrointestinal Tract in Immunocompetent Patients: A Narrative Review. Viruses 2024; 16:346. [PMID: 38543712 PMCID: PMC10975113 DOI: 10.3390/v16030346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 02/17/2024] [Accepted: 02/22/2024] [Indexed: 05/23/2024] Open
Abstract
Cytomegalovirus (CMV) is a potential pathogen that causes gastrointestinal (GI) tract diseases regardless of host immunity. In contrast to immunocompromised individuals, immunocompetent patients lack a comprehensive overview of the gastrointestinal manifestations. This study aims to provide a comprehensive summary of the current evidence regarding presentations, diagnostics, management, risk assessment, and outcomes in immunocompetent patients with CMV GI disease. A thorough literature search of English publications up to April 2022 was conducted across electronic databases to identify relevant articles, with eligible case series selected for detailed analysis. The majority of immunocompetent patients affected by CMV GI disease are typically elderly, critically ill, or burdened with comorbidities that compromise immunity. Clinical presentations range from subtle symptoms to severe surgical conditions, including instances of mortality. Specific clinical presentations, blood test results, or endoscopic features are lacking, necessitating reliance on histopathological tests such as immunohistochemistry staining for diagnosis. While antiviral therapy may offer benefits in improving outcomes, careful individual assessment is warranted due to diverse comorbidities and potential side effects. Mortality rates vary considerably based on underlying medical conditions and therapeutic approaches. It is imperative for clinicians to maintain vigilance for CMV GI disease among high-risk groups, despite their baseline immunocompetence, in order to enhance clinical outcomes.
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Affiliation(s)
- Pai-Jui Yeh
- Department of Pediatric Gastroenterology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (P.-J.Y.); (M.-W.L.); (C.-C.C.)
- Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (R.-C.W.); (C.-T.C.)
| | - Ren-Chin Wu
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (R.-C.W.); (C.-T.C.)
- Department of Pathology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
| | - Chyi-Liang Chen
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-L.C.); (C.-H.C.)
| | - Cheng-Tang Chiu
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (R.-C.W.); (C.-T.C.)
- Department of Pathology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan;
- Taiwan Association of the Study of Small Intestinal Disease, Taoyuan 333, Taiwan
| | - Ming-Wei Lai
- Department of Pediatric Gastroenterology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (P.-J.Y.); (M.-W.L.); (C.-C.C.)
- Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (R.-C.W.); (C.-T.C.)
| | - Chien-Chang Chen
- Department of Pediatric Gastroenterology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (P.-J.Y.); (M.-W.L.); (C.-C.C.)
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (R.-C.W.); (C.-T.C.)
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (C.-L.C.); (C.-H.C.)
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
| | - Yu-Bin Pan
- Biostatistical Section, Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan;
| | - Wey-Ran Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan;
| | - Puo-Hsien Le
- Liver Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan
- Inflammatory Bowel Disease Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan; (R.-C.W.); (C.-T.C.)
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan 333, Taiwan;
- Taiwan Association of the Study of Small Intestinal Disease, Taoyuan 333, Taiwan
- Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
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17
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Andersen HV, Jørgensen VRL, Steensen M, Pedersen FM, Helleberg M. Superinfections in COVID-19 patients receiving extracorporeal membrane oxygenation support. Acta Anaesthesiol Scand 2023; 67:755-761. [PMID: 36906734 DOI: 10.1111/aas.14228] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/12/2023] [Accepted: 02/16/2023] [Indexed: 03/13/2023]
Abstract
BACKGROUND The risk of superinfections and associations with mortality among patients with corona virus disease 2019 (COVID-19) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) is poorly elucidated. METHOD We identified all patients with COVID-19 treated with VV-ECMO >24 h at Rigshospitalet, Denmark from March 2020 to December 2021. Data were obtained by review of medical files. Associations between superinfections and mortality were assessed by logistic regression analyses adjusted for sex and age. RESULTS Fifty patients, median age 53 years (interquartile range [IQR] 45-59), 66% male, were included. Median time on VV-ECMO was 14.5 days (IQR 6.3-23.5), 42% were discharged from hospital alive. Bacteremia, ventilator associated pneumonia (VAP), invasive candidiasis, pulmonary aspergillosis, herpes simplex virus, and cytomegalovirus (CMV) were detected in 38%, 42%, 12%, 12%, 14%, and 20% of patients, respectively. No patients with pulmonary aspergillosis survived. CMV was associated with increased risk of death, odds ratio 12.6 (95% confidence interval 1.9-257, p = .05), whereas we found no associations between other superinfections and risk of death. CONCLUSION Bacteremia and VAP are common but does not seem to affect mortality, whereas pulmonary aspergillosis and CMV are associated with poor prognosis among COVID-19 patients treated with VV-ECMO.
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Affiliation(s)
| | - Vibeke R L Jørgensen
- Department of Thoracic Anesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Morten Steensen
- Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Finn M Pedersen
- Department of Thoracic Anesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Marie Helleberg
- CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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18
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Trirattanapikul A, Pasomsub E, Siriyotha S, Pattanaprateep O, Phuphuakrat A. Diagnostic stewardship to limit repeat plasma cytomegalovirus viral load testing. BMC Infect Dis 2023; 23:387. [PMID: 37296377 DOI: 10.1186/s12879-023-08355-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 05/27/2023] [Indexed: 06/12/2023] Open
Abstract
BACKGROUND Frequent serial monitoring of plasma cytomegalovirus (CMV) viral load caused unnecessary budgets for laboratory testing without changes in treatment. We aimed to implement diagnostic stewardship to limit CMV viral load testing at appropriate intervals. METHODS A quasi-experimental study was performed. To avoid unnecessary plasma CMV viral load testing, the inpatient electronic pop-up reminder was launched in 2021. In cases with plasma CMV viral load testing was ordered in intervals of less than five days, telephone interview and feedback were performed. Pre-post intervention data was compared in terms of clinical and monetary outcomes. The rate of plasma CMV viral load testing performed in intervals of less than five days was compared between 2021 and 2019 using the Poisson regression model. RESULTS After the protocol implementation, there was a significant decrease in the rate of plasma CMV viral load test orders in intervals of less than five days from 17.5% to 8.0% [incidence rate ratio 0.40, p < 0.001]. There was no statistically significant difference in the incidence of CMV DNAemia and CMV disease (p = 0.407 and 0.602, respectively). As a result, the hospital could save the costs of plasma CMV viral load testing per 1,000 patients performed with intervals of less than five days from 2,646,048.11 to 1,360,062.89 Thai Baht. CONCLUSIONS The diagnostic stewardship program is safe and helpful in reducing unnecessary plasma CMV viral load testing and costs.
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Affiliation(s)
- Akeatit Trirattanapikul
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand
| | - Ekawat Pasomsub
- Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Sukanya Siriyotha
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Oraluck Pattanaprateep
- Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Angsana Phuphuakrat
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok, 10400, Thailand.
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19
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Ye Q, Wang J, Chen M, Nie W, Zhang H, Su X, Ling L, Liu X, Liu L, Wang C, Gao Y. Interferon-gamma FlowSpot assay for the measurement of the T-cell response to cytomegalovirus. Heliyon 2023; 9:e16792. [PMID: 37360105 PMCID: PMC10285093 DOI: 10.1016/j.heliyon.2023.e16792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 02/15/2023] [Accepted: 05/29/2023] [Indexed: 06/28/2023] Open
Abstract
Objectives We describe a new method, FlowSpot, to assess CMV-specific T-cell response by quantification of interferon-gamma (IFN-γ). CMV-specific, T-cell-released IFN-γ was captured by flow beads and measured via flow cytometry. In the present study, we used FlowSpot to assess CMV-specific T-cell response in healthy individuals. The FlowSpot results were compared with those of serological analysis and enzyme-linked immunospot (ELISpot) assay. Methods Experimental results and parameter analysis were investigated by using serological, ELISpot, and FlowSpot assays. Results The levels of IFN-γ, which is released from CMV-specific T-cells, were measured, and the results and parameter analysis showed a good correlation between FlowSpot and ELISpot. However, FlowSpot was more sensitive and better reflected the strength of IFN-γ secretion than did ELISpot. Conclusions Compared to ELISpot, FlowSpot has a high sensitivity and is cost and time effective. Thus, this method can be used in wider clinical and scientific applications.
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Affiliation(s)
- Qianyu Ye
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiali Wang
- Department of Nephrology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Weijian Nie
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huanxi Zhang
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaojun Su
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Liuting Ling
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | | | - Longshan Liu
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Changxi Wang
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yifang Gao
- Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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20
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Schinas G, Moustaka V, Polyzou E, Almyroudi MP, Dimopoulos G, Akinosoglou K. Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment. Viruses 2023; 15:v15051165. [PMID: 37243251 DOI: 10.3390/v15051165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 05/10/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic.
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Affiliation(s)
| | - Vasiliki Moustaka
- Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Eleni Polyzou
- Medical School, University of Patras, 26504 Patras, Greece
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, 26504 Patras, Greece
| | - Maria Panagiota Almyroudi
- Department of Emergency Medicine, University Hospital ATTIKON, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - George Dimopoulos
- 3rd Department of Critical Care, EVGENIDIO Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece
| | - Karolina Akinosoglou
- Medical School, University of Patras, 26504 Patras, Greece
- Department of Internal Medicine and Infectious Diseases, University General Hospital of Patras, 26504 Patras, Greece
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21
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Ohta R, Naito Y, Nishikura N, Inoue K, Sano C. Thrombocytopenia in Anti-neutrophil Cytoplasmic Antibody-Associated Vasculitis Indicating the Presence of Cytomegalovirus Infection: A Case Report. Cureus 2023; 15:e38850. [PMID: 37303320 PMCID: PMC10256278 DOI: 10.7759/cureus.38850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/10/2023] [Indexed: 06/13/2023] Open
Abstract
Although cytomegalovirus (CMV) usually colonizes the human body without causing symptoms, CMV infections often develop in immunocompromised hosts. Immunosuppression can trigger CMV infection, and its prediction is essential; however, this is challenging without specific criteria. We present the case of an 87-year-old male patient who visited a rural community hospital with the chief complaint of persistent cough, productive of bloody sputum. Initially, the patient developed thrombocytopenia without any abnormalities of liver function; however, a positive myeloperoxidase antineutrophil cytoplasmic antibody (ANCA) test and the presence of alveolar hemorrhage and glomerulonephritis confirmed ANCA-associated vasculitis. The patient's symptoms and thrombocytopenia resolved transiently after treatment with prednisolone and rituximab. However, the recurrence of thrombocytopenia and the appearance of urinary intracytoplasmic inclusion bodies during the treatment course were investigated using an antigenemia test, which ultimately confirmed CMV viremia. Valganciclovir treatment resolved all the symptoms. This case report showed that thrombocytopenia might indicate the presence of CMV infection in ANCA-associated vasculitis and that intracytoplasmic inclusion bodies in immunosuppressed patients require investigation of CMV infection for effective treatment.
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Affiliation(s)
| | - Yumi Naito
- Community Care, Unnan City Hospital, Unnan, JPN
| | | | | | - Chiaki Sano
- Community Medicine Management, Shimane University Faculty of Medicine, Izumo, JPN
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22
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Abstract
Infections are the leading cause of mortality in burn patients who survive their initial resuscitation. Burn injury leads to immunosuppression and a dysregulated inflammatory response which can have a prolonged impact. Early surgical excision along with support of the multidisciplinary burn team has improved mortality in burn patients. The authors review diagnostic and therapeutic challenges as well as strategies for management of burn related infections.
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23
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Diaz-Decaro J, Myers E, Mucha J, Neumann M, Lewandowski W, Kaczanowska M, Schmidt E, Natenshon A, Talarico C, Buck PO. A systematic literature review on the humanistic burden of cytomegalovirus. Curr Med Res Opin 2023; 39:739-750. [PMID: 36938652 DOI: 10.1080/03007995.2023.2191477] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/21/2023]
Abstract
OBJECTIVE Cytomegalovirus (CMV) infection is typically asymptomatic in healthy individuals; however, certain populations are vulnerable to infection and may develop serious sequelae. CMV infection may also have a broad impact on humanistic outcomes, including patient health status and quality of life (QoL). We conducted a systematic literature review (SLR) to describe the global humanistic burden of CMV and congenital CMV (cCMV) infections across all age groups. METHODS Medline, Embase, and LILACS were searched to identify studies on humanistic outcomes following CMV infection, including health status/QoL and any outcomes in domains such as auditory, cognitive ability, developmental status, intelligence, language, memory, mental health, motor performance, social communication, speech, and vocabulary. The SLR included articles published from 2000-2020 and focused geographically on Australia, Europe, Israel, Japan, Latin America, and North America. RESULTS Sixty-three studies met the inclusion criteria. In general, individuals with symptomatic cCMV infection experience a greater burden of disease and more substantial impact on QoL versus those with asymptomatic cCMV infection. Children with hearing loss due to cCMV infection, both symptomatic and asymptomatic, showed improved auditory outcomes following cochlear implantation. Newborns, infants, and children with cCMV infections had worse cognitive outcomes in psychological development, sequential and simultaneous processing, phonological working memory, and attention control versus age-matched controls without cCMV infection. CMV infection was also associated with cognitive decline in elderly populations. CONCLUSIONS CMV infection can have substantial, lifelong, heterogenous impacts on humanistic outcomes, including health status and QoL, which should be considered when developing and implementing treatment and prevention strategies.
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Affiliation(s)
| | - Evan Myers
- Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA
| | | | | | - Witold Lewandowski
- Certara, Inc., Krakow, Poland
- Certara, Inc., employee at the time of the study
| | | | | | | | - Carla Talarico
- Moderna, Inc., Cambridge, MA, USA
- Moderna, Inc., employee at the time of the study
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24
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Shen HC, Feng JY, Sun CY, Huang JR, Chen YM, Chen WC, Yang KY. Analysis of the effect of cytomegalovirus infection in clinical outcomes and prolonged duration of SARS-CoV-2 shedding in intensive care unit patients with COVID-19 pneumonia. Ther Adv Respir Dis 2023; 17:17534666231209150. [PMID: 37949827 PMCID: PMC10640799 DOI: 10.1177/17534666231209150] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Accepted: 10/05/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is a global outbreak disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cytomegalovirus (CMV) infection can occur in critical COVID-19 patients and is associated with adverse clinical outcomes. OBJECTIVE The aim of this study was to explore the clinical characteristics and outcome of CMV infection in critical COVID-19 patients. DESIGN This was a retrospective cohort study. METHODS From May to September 2021, SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with intensive care unit (ICU) admission were enrolled. CMV infection was confirmed by PCR. Baseline characteristics, critical illness data and clinical outcomes were recorded and analyzed. RESULTS Seventy-two RT-PCR-confirmed COVID-19 patients with ICU admission were included during the study period and 48 (66.7%) patients required mechanical ventilation (MV). Overall, in-hospital mortality was 19.4%. Twenty-one (29.2%) patients developed CMV infection. Patients with CMV infection had a higher likelihood of diabetes, higher lactate dehydrogenase and lactate levels, and higher proportions of MV, anticoagulant, and steroid use. Patients with CMV infection were associated with longer duration of SARS-CoV-2 shedding, longer ICU and hospital stay, and fewer ventilator-free days. The independent risk factor for development of CMV infection was a higher accumulative steroid dose. CONCLUSION CMV infection adversely impacted the outcomes of critical COVID-19 patients, resulting in longer ICU stays, longer mechanical ventilation uses and prolonged shedding of SARS-CoV-2.
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Affiliation(s)
- Hsiao-Chin Shen
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei
- Department of Medical Education, Taipei Veterans General Hospital, Taipei
| | - Jia-Yih Feng
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Chuan-Yen Sun
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei
| | - Jhong-Ru Huang
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei
| | - Yuh-Min Chen
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Wei-Chih Chen
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei
- Institute of Emergency and Critical Care Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Kuang-Yao Yang
- Department of Chest Medicine, Taipei Veterans General Hospital, Institute of Emergency and Critical Care Medicine and School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, #201, Sec. Shih-Pai Road, Taipei 11217
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25
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Saura O, Chommeloux J, Levy D, Assouline B, Lefevre L, Luyt CE. Updates in the management of respiratory virus infections in ICU patients: revisiting the non-SARS-CoV-2 pathogens. Expert Rev Anti Infect Ther 2022; 20:1537-1550. [PMID: 36220790 DOI: 10.1080/14787210.2022.2134116] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Although viruses are an underestimated cause of community-acquired pneumonias (CAP) and hospital-acquired pneumonias (HAP)/ventilator-associated pneumonias (VAP) in intensive care unit (ICU) patients, they have an impact on morbidity and mortality. AREAS COVERED In this perspective article, we discuss the available data regarding the management of severe influenza CAP and herpesviridae HAP/VAP. We review diagnostic and therapeutic strategies in order to give clear messages and address unsolved questions. EXPERT OPINION Influenza CAP affects yearly thousands of people; however, robust data regarding antiviral treatment in the most critical forms are scarce. While efficacy of oseltamivir has been investigated in randomized controlled trials (RCT) in uncomplicated influenza, only observational data are available in ICU patients. Herpesviridae are an underestimated cause of HAP/VAP in ICU patients. Whilst incidence of herpesviridae identification in samples from lower respiratory tract of ICU patients is relatively high (from 20% to 50%), efforts should be made to differentiate local reactivation from true lung infection. Only few randomized controlled trials evaluated the efficacy of antiviral treatment in herpesviridae reactivation/infection in ICU patients and all were exploratory or negative. Further studies are needed to evaluate the impact of such treatment in specific populations.
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Affiliation(s)
- Ouriel Saura
- Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Juliette Chommeloux
- Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Paris, France.,Sorbonne Université, GRC 30, RESPIRE, UMRS 1166, ICAN Institute of Cardiometabolism and Nutrition, Paris, France
| | - David Levy
- Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Benjamin Assouline
- Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Lucie Lefevre
- Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Paris, France.,Sorbonne Université, GRC 30, RESPIRE, UMRS 1166, ICAN Institute of Cardiometabolism and Nutrition, Paris, France
| | - Charles-Edouard Luyt
- Médecine Intensive Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Paris, France.,Sorbonne Université, GRC 30, RESPIRE, UMRS 1166, ICAN Institute of Cardiometabolism and Nutrition, Paris, France
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26
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Chen J, Song J, Dai L, Post SR, Qin Z. SARS-CoV-2 infection and lytic reactivation of herpesviruses: A potential threat in the postpandemic era? J Med Virol 2022; 94:5103-5111. [PMID: 35819034 PMCID: PMC9350099 DOI: 10.1002/jmv.27994] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/07/2022] [Accepted: 07/08/2022] [Indexed: 02/06/2023]
Abstract
The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative pathogen for the coronavirus disease 2019 (COVID-19) pandemic, has greatly stressed our healthcare system. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal disease outcomes, including chronic viral infections. Increasing cases of lytic reactivation of human herpesviruses in COVID-19 patients and vaccinated people have been reported recently. SARS-CoV2 coinfection, COVID-19 treatments, and vaccination may aggravate those herpesvirus-associated diseases by reactivating the viruses in latently infected host cells. In this review, we summarize recent clinical findings and limited mechanistic studies regarding the relationship between SARS-CoV-2 and different human herpesviruses that suggest an ongoing potential threat to human health in the postpandemic era.
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Affiliation(s)
- Jungang Chen
- Department of Pathology, Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
| | - Jiao Song
- Department of Pathology, Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
| | - Lu Dai
- Department of Pathology, Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
| | - Steven R. Post
- Department of Pathology, Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
| | - Zhiqiang Qin
- Department of Pathology, Winthrop P. Rockefeller Cancer InstituteUniversity of Arkansas for Medical SciencesLittle RockArkansasUSA
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27
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Pavlinac PB, Singa B, Huang ML, Shrestha L, Li V, Atlas HE, Diakhate MM, Brander R, Meshak L, Bogonko G, Tickell KD, McGrath CJ, Machuara IM, Ounga DO, Berkley JA, Richardson BA, John-Stewart G, Walson JL, Slyker J. Cytomegalovirus Viremia Predicts Postdischarge Mortality in Kenyan HIV-Exposed Uninfected Children. J Infect Dis 2022; 226:1519-1527. [PMID: 35152295 PMCID: PMC9624454 DOI: 10.1093/infdis/jiac047] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Accepted: 02/11/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) viremia is associated with mortality in severely ill immunocompetent adults and hospitalized children with HIV (CWH). We measured CMV viremia in HIV-exposed and -unexposed Kenyan children aged 1-59 months discharged from hospital and determined its relationship with postdischarge mortality. METHODS CMV DNA levels were measured in plasma from 1024 children (97 of which were HIV exposed uninfected [HEU], and 15 CWH). Poisson and Cox proportional hazards regression models were used to identify correlates of CMV viremia ≥ 1000 IU/mL
and estimate associations with 6-month mortality, respectively. RESULTS CMV viremia was detected in 31% of children, with levels ≥ 1000 IU/mL in 5.8%. HIV infection, age < 2 years, breastfeeding, and midupper arm circumference < 12.5 cm were associated with CMV viremia ≥ 1000 IU/mL. Among HEU children, CMV ≥ 1000 IU/mL (hazard ratio [HR] = 32.0; 95% confidence interval [CI], 2.9-354.0; P = .005) and each 1-log increase in CMV viral load (HR = 5.04; 95% CI, 1.7-14.6; P = .003) were associated with increased risk of mortality. CMV viremia was not significantly associated with mortality in HIV-unexposed children. CONCLUSIONS CMV levels at hospital postdischarge predict increased risk of 6-month mortality in Kenyan HEU children. CMV suppression may be a novel target to reduce mortality in HEU children. CLINICAL TRIAL REGISTRATION NCT02414399.
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Affiliation(s)
- Patricia B Pavlinac
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
| | - Benson Singa
- Kenya Medical Research Institute, Nairobi, Kenya
- Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
| | - Meei-Li Huang
- Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
| | - Lasata Shrestha
- Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
| | - Vanessa Li
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Hannah E Atlas
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | | | - Rebecca Brander
- Department of Global Health, University of Washington, Seattle, Washington, USA
| | - Liru Meshak
- Homa Bay Teaching and Referral Hospital, Homa Bay, Kenya
| | | | - Kirkby D Tickell
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
| | - Christine J McGrath
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
| | | | | | - James A Berkley
- Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya
- Center for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
| | - Barbra A Richardson
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Biostatistics, University of Washington, Seattle, Washington, USA
| | - Grace John-Stewart
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
- Department of Medicine, Allergy, and Infectious Disease, University of Washington, Seattle, Washington, USA
- Department of Pediatrics, University of Washington, Seattle, Washington, USA
| | - Judd L Walson
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
- Childhood Acute Illness and Nutrition Network, Nairobi, Kenya
- Department of Medicine, Allergy, and Infectious Disease, University of Washington, Seattle, Washington, USA
- Department of Pediatrics, University of Washington, Seattle, Washington, USA
| | - Jennifer Slyker
- Department of Global Health, University of Washington, Seattle, Washington, USA
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
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Pourabdollah Toutkaboni M, Hakamifard A, Abtahian Z, Mirahmadian A, Rahdar M, Mokhber Dezfuli M, Tabarsi P. Co-infection of Klebsiella pneumonia, Cytomegalovirus, Aspergillus and Zygomycete in a patient with SARS-CoV-2. Clin Case Rep 2022; 10:e6033. [PMID: 35846907 PMCID: PMC9272201 DOI: 10.1002/ccr3.6033] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/08/2022] [Accepted: 03/15/2022] [Indexed: 11/06/2022] Open
Abstract
Co-infection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens has become a serious threat. There are the reports of fungal, bacterial, and viral co-infections with SARS-CoV-2. We report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia, and also klebsiella pneumoniae empyema as the complication of SARS-CoV-2.
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Affiliation(s)
- Mihan Pourabdollah Toutkaboni
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Atousa Hakamifard
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Zahra Abtahian
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Arefeh Mirahmadian
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Mohammad Rahdar
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Mojtaba Mokhber Dezfuli
- Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
| | - Payam Tabarsi
- Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
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29
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Schoninger S, Dubrovskaya Y, Marsh K, Altshuler D, Prasad P, Louie E, Weisenberg S, Hochman S, Fridman D, Trachuk P. Outcomes of Cytomegalovirus Viremia Treatment in Critically Ill Patients with COVID-19 Infection. Open Forum Infect Dis 2022; 9:ofac286. [PMID: 35859993 PMCID: PMC9214167 DOI: 10.1093/ofid/ofac286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 06/08/2022] [Indexed: 11/14/2022] Open
Abstract
Abstract
Background
Patients with COVID-19 admitted to the intensive care unit (ICU) have poor outcomes and frequently develop comorbid conditions, including cytomegalovirus (CMV) reactivation. The implications of CMV reactivation in this setting are unknown. We aimed to investigate if treatment of CMV viremia improved in-hospital mortality in ICU patients with COVID-19.
Methods
In this single center retrospective study, we analyzed clinical outcomes in patients diagnosed with COVID-19 pneumonia and CMV viremia admitted to an ICU from March 1, 2020, to April 30, 2021, who either received treatment (ganciclovir and/or valganciclovir) or no treatment. The primary outcome was all-cause in-hospital mortality. Secondary outcomes were total hospital length of stay (LOS), ICU LOS, requirement for extracorporeal membrane oxygenation (ECMO) support, duration of mechanical ventilation (MV), and predictors of in-hospital mortality.
Results
A total of 80 patients were included, 43 patients in the treatment group and 37 in the control. Baseline characteristics were similar in both groups. CMV-treated patients were more likely to test positive for CMV earlier in their course, more likely to be on ECMO and received higher total steroid doses on average. In-hospital mortality was similar between the two groups (37.2% vs 43.2.0% p-value = 0.749). There was no significant difference in hospital LOS, though CMV-treated patients had a longer ICU LOS.
Conclusions
Treatment of CMV viremia did not decrease in-hospital mortality in ICU patients with COVID-19, but sample size was limited. CMV viremia was significantly associated with total steroid dose received and longer ICU stay.
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Affiliation(s)
- Scott Schoninger
- Division of Internal Medicine, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - Yanina Dubrovskaya
- Department of Pharmacy, NYU Langone Health, New York , New York , United States
- Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - Kassandra Marsh
- Department of Pharmacy, NYU Langone Health, New York , New York , United States
| | - Diana Altshuler
- Department of Pharmacy, NYU Langone Health, New York , New York , United States
| | - Prithiv Prasad
- Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - Eddie Louie
- Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - Scott Weisenberg
- Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - Sarah Hochman
- Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - David Fridman
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
| | - Polina Trachuk
- Division of Infectious Diseases and Immunology, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University Grossman School of Medicine, New York , New York , United States
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30
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Shah D, Gupta E, Baweja S, Pasupuleti SSR, Maiwall R, Ramalingam A, Mitra LG, Sarin SK. CYTOMEGALOVIRUS REACTIVATION IN SEROPOSITIVE CRITICALLY ILL PATIENTS WITH LIVER CIRRHOSIS: A HOSPITAL-BASED LONGITUDINAL STUDY. JOURNAL OF CLINICAL VIROLOGY PLUS 2022. [DOI: 10.1016/j.jcvp.2022.100087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
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31
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Siddiqui SS, Chatterjee S, Yadav A, Rai N, Agrawal A, Gurjar M, Yadav G, Prakash S, Kumar A, Muzaffar SN. Cytomegalovirus Coinfection in Critically Ill Patients with Novel Coronavirus 2019 Disease: Pathogens or Spectators? Indian J Crit Care Med 2022; 26:376-380. [PMID: 35519914 PMCID: PMC9015933 DOI: 10.5005/jp-journals-10071-24130] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Coronavirus disease-2019 (COVID-19) pandemic is raging all over the world. As we are delving more into management of COVID-19, certain new challenges are emerging. One of these is emergence or reactivation of viral infections belonging to Herpesviridae family, especially cytomegalovirus (CMV). Although we have come across the threat of fungal and resistant bacterial infections, experience regarding reactivation or coinfection with concomitant viral infections like CMV during the COVID pandemic is still limited. Whether CMV is a bystander or pathogen is difficult to say categorically and needs further research. In this case series, we intend to describe three patients of COVID-19 with CMV coinfections. To our knowledge, this is the first case series from India.
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Affiliation(s)
- Suhail S Siddiqui
- Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Soumyadip Chatterjee
- Department of Infectious Diseases, Tata Medical Centre, Kolkata, West Bengal, India
| | - Ambuj Yadav
- Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Nitin Rai
- Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Avinash Agrawal
- Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Mohan Gurjar
- Department of Critical Care Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Geeta Yadav
- Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Shantanu Prakash
- Department of Microbiology (Virology), King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Amit Kumar
- Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Syed N Muzaffar
- Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
- Syed N Muzaffar, Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India, Phone: +91 9648084011, e-mail:
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32
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Sanchez AAR, Apa-ap A, Chua J. Cytomegalovirus Meningoencephalitis in a Critically Ill Elderly Female: A Case Report. Cureus 2022; 14:e22611. [PMID: 35371829 PMCID: PMC8958049 DOI: 10.7759/cureus.22611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2022] [Indexed: 11/27/2022] Open
Abstract
Cytomegalovirus (CMV) disease is usually a mild and self-limiting disease in immunocompetent patients. Recent evidence shows that CMV infection may also develop in the setting of critical illness, burn and sepsis and is usually associated with increased mortality rate and prolonged ICU stay. This paper describes an 83-year-old female who was initially admitted as a case of community-acquired pneumonia-high risk but remained febrile with paucity of verbal output despite correction of pneumonia and other electrolyte derangements. MRI showed the presence of peculiar-appearing signal abnormalities in the interhemispheric region and the anterior frontal convexities which were suspected to represent secondarily infected fluid collections. On lumbar tap, viral cerebrospinal fluid (CSF) panel showed a positive result for CMV infection. The patient was then given ganciclovir for 14 days followed by valganciclovir for three months. The most notable improvement was noted with the lysis of fever several days after starting anti-viral treatment. Verbal output remained limited, yet, on repeat tap after completion of treatment, CMV viral panel is now negative.
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33
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Kakiuchi T, Eguchi K, Koga D, Eguchi H, Nishi M, Sonoda M, Ishimura M, Matsuo M. Changes in bone marrow and peripheral blood lymphocyte subset findings with onset of hepatitis-associated aplastic anemia. Medicine (Baltimore) 2022; 101:e28953. [PMID: 35212305 PMCID: PMC8878616 DOI: 10.1097/md.0000000000028953] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/11/2022] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Hepatitis-associated aplastic anemia (HAAA) is a rare illness that results in bone marrow failure following hepatitis development. The etiological agent remains unknown in most HAAA cases. However, clinical features of the disease and immunotherapy response indicate that immune-mediated factors play a central role in the pathogenesis of HAAA. Activation of cytotoxic T cells and increase in CD8 cells could exert cytotoxic effects on the myelopoietic cells in the bone marrow. PATIENT CONCERNS A 15-month-old boy was brought to our hospital with complaints of generalized petechiae and purpura observed a week prior to hospitalization. His liver was palpated 3 cm below the costal margin, platelet count was 0 × 104/μL, and alanine aminotransferase level was 1346 IU/L. A blood test indicated cytomegalovirus infection, and 3 bone marrow examinations revealed progressive HAAA. As the disease progressed to the 3rd, 6th, and 9th week after onset, CD4+ T cells were markedly decreased, CD8+ T cells were markedly increased, and the CD4/CD8 ratio was significantly decreased. The number of B cells and natural killer cells decreased with time, eventually reaching 0.0%. DIAGNOSIS HAAA. INTERVENTIONS Rabbit antithymocyte globulin and eltrombopag olamine (a thrombopoietin receptor agonist) were administered. OUTCOMES The patient's platelet count returned to normal, and bone marrow transplantation was avoided. The peripheral blood lymphocytes (PBLs) improved as the patient's general condition recovered. LESSONS This case demonstrates that HAAA induced by cytomegalovirus infection features decreasing CD4+ and increasing CD8+ PBLs as the bone marrow hypoplasia progresses. The PBLs return to their normal levels with the recovery from the disease. Our case findings thus support the involvement of immunological abnormality in HAAA.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Katsuhide Eguchi
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Daisuke Koga
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Hiroi Eguchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Masanori Nishi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Motoshi Sonoda
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masataka Ishimura
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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34
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Cytomegalovirus reactivation in critically-ill Coronavirus Disease 2019 patients: A case series of 11 patients. IDCases 2022; 27:e01402. [PMID: 35036326 PMCID: PMC8748205 DOI: 10.1016/j.idcr.2022.e01402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 01/10/2022] [Accepted: 01/10/2022] [Indexed: 12/15/2022] Open
Abstract
The mortality associated with Coronavirus Disease 2019 is greatly influenced by known risk factors such as elderly age, cardiovascular disease, hypertension, diabetes, and immunosuppression. As cytomegalovirus reactivation in critically ill patients has been linked with higher morbidity and mortality in intensive care settings, it has been suggested that cytomegalovirus reactivation might lead to worse clinical outcomes of patients with Coronavirus Disease 2019. Here we describe the clinical course of 11 patients with Coronavirus Disease 2019 and concomitant cytomegalovirus viremia. We conclude that further research is necessary to formulate guidelines on diagnosis and treatment of cytomegalovirus reactivation in Coronavirus Disease 2019 patients.
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35
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Jung KH, Jung J, Kim MJ, Chong YP, Lee SO, Choi SH, Kim YS, Kim SH. Optimal duration of antiviral treatment in patients with gastrointestinal cytomegalovirus disease at a low and high risk of relapse. Medicine (Baltimore) 2022; 101:e28359. [PMID: 35029881 PMCID: PMC8735784 DOI: 10.1097/md.0000000000028359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 12/01/2021] [Indexed: 11/26/2022] Open
Abstract
We evaluated the association between antiviral treatment duration and relapse of gastrointestinal (GI) cytomegalovirus (CMV) disease by analyzing the risk factors for relapse.Patients who were diagnosed with GI CMV disease at a tertiary hospital from January 2008 to April 2019 were retrospectively enrolled. Patients with relapsed disease were those with a recurrence of GI CMV disease at least 4 weeks after the initial antiviral treatment.Of 238 participants, including 145 (51.9%) with upper and 93 (48.1%) with lower GI CMV diseases, 27 (11.3%) had experienced relapses. The difference in antiviral treatment duration between the relapsed and nonrelapsed GI CMV groups was not significant (median days, 21.0 vs 17.0, P = .13). Multivariate analysis revealed that hematologic malignancy (odds ratio, 3.73; P = .026) and ulcerative colitis (odds ratio, 4.61; P = .003) were independent risk factors for relapse. Participants with at least one of these risk factors and those with no independent risk factors were classified under the high- (relapse rate, 25.9%) and low-risk of relapse groups (relapse rate, 6.7%), respectively. Accordingly, we further stratified 180 (75.6%) and 58 (24.4%) participants under the low- and high-risk of relapse groups, respectively. There was no significant difference in relapse rates between the high- and low-risk groups according to antiviral treatment duration.Approximately 10% of the participants experienced relapses after antiviral treatment, with hematologic malignancy and ulcerative colitis featuring as risk factors. Therefore, prolonged antiviral treatment might not be helpful in preventing GI CMV disease relapse.
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Affiliation(s)
- Kyung Hwa Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Infectious Diseases, Uijeongbu Eulji Medical Center, University of Eulji College of Medicine, Uijeongbu, Republic of Korea
| | - Jiwon Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Jae Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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36
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Yamamoto Y, Shiroyama T, Hirata H, Kuge T, Matsumoto K, Yoneda M, Yamamoto M, Uchiyama A, Takeda Y, Kumanogoh A. Prolonged corticosteroid therapy and cytomegalovirus infection in patients with severe COVID-19. J Med Virol 2021; 94:1067-1073. [PMID: 34708883 PMCID: PMC8661974 DOI: 10.1002/jmv.27421] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/25/2021] [Accepted: 10/26/2021] [Indexed: 01/08/2023]
Abstract
Systemic corticosteroid therapy is frequently used to treat coronavirus disease 2019 (COVID‐19). However, its maximum duration without secondary infections remains unclear. We aimed to evaluate the utility of monitoring cytomegalovirus (CMV) infection in patients with COVID‐19 and estimate the maximum duration of systemic corticosteroid therapy without secondary infections. We included 59 patients with severe COVID‐19 without CMV infection on admission to the intensive care unit (ICU). All patients received systemic corticosteroid therapy under invasive mechanical ventilation, with examination for plasma CMV‐deoxyribonucleic acid (DNA) levels during the ICU stay. We analyzed the correlations among patient characteristics, CMV infection, diseases, and patient mortality. CMV infections were newly identified in 15 (25.4%) patients; moreover, anti‐CMV treatment was administered to six (10.2%) patients during the ICU stay. Four (6.8%) patients had secondary infection‐related mortality. The cumulative incidences of CMV infection and anti‐CMV treatment during the ICU stay were 26.8% (95% confidence interval [CI], 15.8%–39.0%) and 12.3% (95% CI, 4.8%–23.4%), respectively. Furthermore, the median duration of systemic corticosteroid therapy without CMV infection was 15 days (95% CI, 13–16 days). The presence of CMV infection was associated with mortality during the ICU stay (p = 0.003). Monitoring plasma CMV‐DNA levels could facilitate the detection of secondary CMV infection due to prolonged systemic corticosteroid therapy. The duration of systemic corticosteroid therapy for COVID‐19 should be limited.
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Affiliation(s)
- Yuji Yamamoto
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Takayuki Shiroyama
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Haruhiko Hirata
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tomoki Kuge
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kinnosuke Matsumoto
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Midori Yoneda
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Makoto Yamamoto
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Akinori Uchiyama
- Department of Anesthesiology and Intensive Care Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Yoshito Takeda
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Kumanogoh
- Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.,Department of Immunopathology, WPI, Immunology Frontier Research Center (iFReC), Osaka University, Suita, Osaka, Japan.,Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan.,Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Suita, Osaka, Japan
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37
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Abstract
Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated with profound and sustained immunosuppression, which has been implicated as a predisposing factor in the increased susceptibility of patients to secondary infections and mortality. In this review, we discuss mechanisms of sepsis-induced immunosuppression and biomarkers that identify a state of impaired immunity. We also highlight immune-enhancing strategies that have been evaluated in patients with sepsis, as well as therapeutics under current investigation. Finally, we describe future challenges and the need for a new treatment paradigm, integrating predictive enrichment with patient factors that may guide the future selection of tailored immunotherapy. Expected final online publication date for the Annual Review of Physiology, Volume 84 is February 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Lisa K Torres
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York-Presbyterian Hospital-Weill Cornell Medicine, New York, NY, USA;
| | - Peter Pickkers
- Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands;
| | - Tom van der Poll
- Center of Experimental and Molecular Medicine, Division of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands;
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38
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Xu Y, Chen M, Xie L, Zhang X, Wang Y, Gu X. Cytomegalovirus-Associated Nephrotic Syndrome in a Patient with Myasthenia Gravis Treated with Azathioprine: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2021; 22:e933380. [PMID: 34582431 PMCID: PMC8488190 DOI: 10.12659/ajcr.933380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/16/2021] [Accepted: 08/09/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Patients taking azathioprine (AZA) are very susceptible to development of cytomegalovirus (CMV) infection. The symptoms of CMV infection are varied. In some rare cases, CMV infection can even result in nephrotic syndrome. CASE REPORT Here, we present a rare case of nephrotic syndrome associated with CMV infection, induced by azathioprine intake. The patient, diagnosed with myasthenia gravis, was initially treated with azathioprine for 2 years. Then, the patient was admitted to the hospital due to nephrotic syndrome and acute kidney injury. Minimal change disease with acute tubular necrosis were diagnosed through biopsy. After an initial good response to hemodialysis and steroids, the patient developed severe pneumonia and oral ulcers. Further anti-CMV IHC staining of kidney tissues showed positive cells in tubules, indicating nephrotic syndrome secondary to CMV infection. CONCLUSIONS This case reminded us that CMV may be an under-recognized cause of nephrotic syndrome. Patients treated with azathioprine are very susceptible to developing CMV infection. During the diagnosis of nephrotic syndrome, we should always take CMV infection into consideration, especially in patients with on azathioprine.
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39
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Hunter-Schlichting D, Kelsey KT, Demmer R, Patel M, Bueno R, Christensen B, Fujioka N, Kolarseri D, Nelson HH. Cytomegalovirus infection in malignant pleural mesothelioma. PLoS One 2021; 16:e0254136. [PMID: 34383785 PMCID: PMC8360519 DOI: 10.1371/journal.pone.0254136] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 06/18/2021] [Indexed: 11/19/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes.
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Affiliation(s)
- DeVon Hunter-Schlichting
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, United States of America
- Masonic Cancer Center University of Minnesota Twin Cities, Minneapolis, Minnesota, United States of America
| | - Karl T. Kelsey
- Department of Epidemiology and Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, United States of America
| | - Ryan Demmer
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Manish Patel
- Division of Hematology and Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Raphael Bueno
- Division of Thoracic Surgery, Lung Center and International Mesothelioma Program, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Brock Christensen
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America
| | - Naomi Fujioka
- Division of Hematology and Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Deepa Kolarseri
- Masonic Cancer Center University of Minnesota Twin Cities, Minneapolis, Minnesota, United States of America
| | - Heather H. Nelson
- Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, United States of America
- Masonic Cancer Center University of Minnesota Twin Cities, Minneapolis, Minnesota, United States of America
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Abstract
BACKGROUND The pharmacokinetic (PK) data of ganciclovir (GCV), a first-line antiviral treatment for cytomegalovirus infections, in critically ill patients are limited. This study aimed at characterizing GCV population PK and interindividual variability (IIV) in intensive care unit (ICU) patients. Secondary objectives were to identify patient characteristics responsible for IIV and simulate GCV exposure for different dosing regimens. METHOD In this retrospective observational study, clinical data and serum GCV levels were collected from ICU patients on intravenous GCV. PK modeling, covariate analyses, and explorative Monte Carlo dosing simulations (MCS) were performed using nonlinear mixed-effects modeling. Bootstrap and visual predictive checks were used to determine model adequacy. RESULTS In total, 128 GCV measurements were obtained from 34 patients. GCV PK conformed to a 1-compartment model with first-order elimination. After multivariate analyses, only the estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (P < 0.001) was included as a covariate. In the final model, the estimated clearance (CL) and volume of distribution (V1) were 2.3 L/h and 42 L, respectively, for a patient with the median CKD-EPI of the population (65 mL/min per 1.73 m). The association between CKD-EPI and CL decreased the residual variability from 0.56 to 0.43 and V1-IIV from 114% to 80%, whereas CL-IIV changed from 43% to 47%. MCS revealed that a substantial number of patients may not achieve the GCV PK/pharmacodynamic target trough level (>1.5 mg/L) when administering the label-recommended dose reductions for patients with CKD-EPI <50 mL/min. CONCLUSIONS A large IIV was observed in GCV PK among ICU patients. CKD-EPI could partially explain the IIV, although a large part of the variability remains unclear. MCS suggested that recommended dose reductions for CKD-EPI <50 mL/min may lead to subtherapeutic plasma GCV levels in these patients.
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Park GE, Ki HK, Ko JH. Impact of antiviral treatment on long-term prognosis in non-immunocompromised patients with CMV reactivation. BMC Infect Dis 2021; 21:414. [PMID: 33947335 PMCID: PMC8094573 DOI: 10.1186/s12879-021-06098-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 04/19/2021] [Indexed: 11/29/2022] Open
Abstract
Background Reactivation of human cytomegalovirus (CMV) occurs in non-immunocompromised patients with or without specific organ involvement, but it is still unknown whether it has a clinical implication on long-term prognosis or not. Methods A retrospective cohort study evaluating non-immunocompromised adult patients with CMV reactivation was conducted during the period between January 2010 and February 2018. Patients were divided into ganciclovir-treated and non-treated groups. Patients who died within 30 days from CMV reactivation were excluded as they died from complex causes of conditions. Survivors were followed for 30-months to evaluate long-term prognosis. Results A total of 136 patients with CMV reactivation was included, consisting of 66 ganciclovir-treated (48.5%) and 70 non-treated (51.5%) patients. Overall, patients were old-aged (median 70 years old) and most were treated with pneumonia of any cause (91.2%). More patients in ganciclovir-treated group were treated at intensive care unit (43.9% vs 24.3%, respectively) and had higher viral load over 5000 copies/ml (48.5% vs 22.9%) than non-treated group (all P < 0.05). Primary and secondary endpoints including 30-months survival (28.0 vs 38.9%, respectively) and 12-months survival (40.3% vs 49.2%) were not statistically different between the ganciclovir-treated and non-treated groups. In the multivariate analyses, ganciclovir treatment was not associated with 30-months survival (HR 1.307, 95% CI 0.759–2.251) and 12-months survival (HR 1.533, 95% CI 0.895–2.624). Conclusion In a retrospective cohort study evaluating non-immunocompromised patients with CMV reactivation, ganciclovir treatment was not associated with long-term prognosis. Antiviral treatment in this condition would not be necessary unless organ involvement is suspected. Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06098-4.
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Affiliation(s)
- Ga Eun Park
- Division of Infectious Disease, Konkuk University medical center, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Hyun Kyun Ki
- Division of Infectious Disease, Konkuk University medical center, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Jae-Hoon Ko
- Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
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Kuo CW, Wang SY, Tsai HP, Su PL, Cia CT, Lai CH, Chen CW, Shieh CC, Lin SH. Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 55:291-299. [PMID: 33840605 DOI: 10.1016/j.jmii.2021.03.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 02/23/2021] [Accepted: 03/08/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND/PURPOSE Cytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown. METHODS We retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression. RESULTS A total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26-12.60 and 2.64-28.82; p value = 0.019 and <0.001, respectively.). Patients with detectable CMV in BAL fluid did not have higher IPA risk (crude odds ratio, 0.95; 95% CI, 0.33-2.79; p value = 0.933). After stratifying patients by CMV viral load, the IPA risk is higher for patients with higher viral loads. There is an additive synergistic effect on IPA risk between CMV viremia and influenza infection. CONCLUSION For critically ill patients, CMV viremia is an independent risk factor of IPA. Patients with higher blood CMV viral loads have a higher risk of IPA. CMV viremia and influenza have an additive synergistic effect for IPA risk in critically ill patients.
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Affiliation(s)
- Chin-Wei Kuo
- Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Critical Care Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Sheng-Yuan Wang
- Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Huey-Pin Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Po-Lan Su
- Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Cong-Tat Cia
- Division of Critical Care Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center for Infection Control, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ching-Han Lai
- Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chang-Wen Chen
- Division of Chest Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Division of Critical Care Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chi-Chang Shieh
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Sheng-Hsiang Lin
- Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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43
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Valganciclovir-Ganciclovir Use and Systematic Therapeutic Drug Monitoring. An Invitation to Antiviral Stewardship. Antibiotics (Basel) 2021; 10:antibiotics10010077. [PMID: 33467490 PMCID: PMC7831032 DOI: 10.3390/antibiotics10010077] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/07/2021] [Accepted: 01/11/2021] [Indexed: 11/24/2022] Open
Abstract
Valganciclovir (VGCV) and ganciclovir (GCV) doses must be adjusted according to indication, renal function and weight. No specific therapeutic exposure values have been established. We aimed to evaluate the adequacy of VGCV/GCV doses, to assess the interpatient variability in GCV serum levels, to identify predictive factors for this variability and to assess the clinical impact. This is a prospective study at a tertiary institution including hospitalized patients receiving VGCV/GCV prophylaxis or treatment. Adequacy of the antiviral dose was defined according to cytomegalovirus guidelines. Serum levels were determined using High-Performance Liquid Chromatography. Blood samples were drawn at least 3 days after antiviral initiation. Outcome was considered favorable if there was no evidence of cytomegalovirus infection during prophylaxis or when a clinical and microbiological resolution was attained within 21 days of treatment and no need for drug discontinuation due to toxicity. Seventy consecutive patients [74.3% male/median age: 59.2 years] were included. VGCV was used in 25 patients (35.7%) and GCV in 45 (64.3%). VGCV/GCV initial dosage was deemed adequate in 47/70 cases (67.1%), lower than recommended in 7/70 (10%) and higher in 16/70 (22.9%). Large inter-individual variability of serum levels was observed, with median trough levels of 2.3 mg/L and median peak levels of 7.8 mg/L. Inadequate dosing of VGCV/GCV and peak levels lower than 8.37 or greater than 11.86 mg/L were related to poor outcome. Further studies must be performed to confirm these results and to conclusively establish if VGCV/GCV therapeutic drug monitoring could be useful to improve outcomes in specific clinical situations.
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Khatib MY, Shaik KS, Ahmed AA, Alwraidat MA, Mohamed AS, Abou Kamar MR, Sharaf Eldean MZ, Aldaraiseh BK, Nashwan AJ. Tocilizumab-induced cytomegalovirus colitis in a patient with COVID-19. Clin Case Rep 2021; 9:148-152. [PMID: 33489151 PMCID: PMC7813092 DOI: 10.1002/ccr3.3487] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 09/25/2020] [Accepted: 10/12/2020] [Indexed: 12/20/2022] Open
Abstract
The authors urge clinicians to observe for early signs of CMV reactivation in patients presenting with gastrointestinal bleeding and intestinal perforation after receiving tocilizumab or other immunosuppressive therapy as a treatment for COVID 19. Early recognition of CMV infection and treatment will prevent life-threatening bleeding and mortality.
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Affiliation(s)
- Mohamad Y. Khatib
- Critical Care UnitHazm Mebaireek General Hospital (HMGH)Hamad Medical Corporation (HMC)DohaQatar
| | - Karimulla S. Shaik
- Critical Care UnitHazm Mebaireek General Hospital (HMGH)Hamad Medical Corporation (HMC)DohaQatar
| | - Amna A. Ahmed
- Critical Care UnitHazm Mebaireek General Hospital (HMGH)Hamad Medical Corporation (HMC)DohaQatar
| | - Mohammad A. Alwraidat
- Critical Care UnitHazm Mebaireek General Hospital (HMGH)Hamad Medical Corporation (HMC)DohaQatar
| | - Ahmed S. Mohamed
- Critical Care UnitHazm Mebaireek General Hospital (HMGH)Hamad Medical Corporation (HMC)DohaQatar
| | - Mohamad R. Abou Kamar
- Department of Infectious DiseasesCommunicable Disease Center (CDC)Hamad Medical Corporation (HMC)DohaQatar
| | | | - Bashar K. Aldaraiseh
- Department of Laboratory Medicine and Pathology (DLMP)Hamad Medical Corporation (HMC)DohaQatar
| | - Abdulqadir J. Nashwan
- Critical Care UnitHazm Mebaireek General Hospital (HMGH)Hamad Medical Corporation (HMC)DohaQatar
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45
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Abstract
Ophthalmic disease encountered in the intensive care unit (ICU) has a wide spectrum of prevalence and severity. Prolonged exposure of the cornea is common and preventable. Trauma, glaucoma, infection, vascular disease, and burns are among the potential causes of vision loss. Patients are predisposed to ocular complications by the ICU environment and critical illness itself. Critically ill patients require prioritization of life-sustaining interventions, and less emphasis is placed on ophthalmic disease, leading to missed opportunities for vision-saving intervention. It is therefore imperative for intensivists, nurses, and other providers to have an increased awareness and understanding of the broad range of ocular conditions potentially seen in the ICU.
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46
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Kadambari S, Klenerman P, Pollard AJ. Why the elderly appear to be more severely affected by COVID-19: The potential role of immunosenescence and CMV. Rev Med Virol 2020; 30:e2144. [PMID: 32671966 PMCID: PMC7404358 DOI: 10.1002/rmv.2144] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/25/2020] [Accepted: 06/26/2020] [Indexed: 12/21/2022]
Abstract
The significantly higher mortality rates seen in the elderly compared with young children during the coronavirus disease 2019 (Covid‐19) pandemic is likely to be driven in part by an impaired immune response in older individuals. Cytomegalovirus (CMV) seroprevalence approaches 80% in the elderly. CMV has been shown to accelerate immune ageing by affecting peripheral blood T cell phenotypes and increasing inflammatory mediated cytokines such as IL‐6. The elderly with pre‐existing but clinically silent CMV infection may therefore be particularly susceptible to severe Covid‐19 disease and succumb to a cytokine storm which may have been promoted by CMV. Here, we evaluate the potential role of CMV in those with severe Covid‐19 disease and consider how this relationship can be investigated in current research studies.
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Affiliation(s)
- Seilesh Kadambari
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK
| | - Paul Klenerman
- Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK
| | - Andrew J Pollard
- Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK
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47
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Abstract
Background: Viral infections after burns are less common than bacterial infections but usually occur in the more severely burned patients and have been associated with poor outcomes. Methods: Retrospective reviews and case series were examined to provide an overview of the management of viral infections in the burn patient. Results: The most common viral pathogens in these patients are the herpesviruses, which include herpes simplex, varicella zoster, cytomegalovirus, and human herpesvirus 6. Established viral infections that may complicate patient management include human immunodeficiency virus, hepatitis B and C, and, more recently, the novel coronavirus SARS-CoV-2. Herpesvirus infections can occur as primary or nosocomial pathogens but clinical manifestations most commonly are re-activation of latent viral infection. Because of the paucity of data in the burn population, much of the evidence for specific treatments is extrapolated from patients with severe immunosuppression or critical illness. Antiviral therapy is employed for the burn patient with herpesvirus infections. This is an area of active study, and further research is needed to better understand the risks, clinical manifestations, and attributable morbidity and mortality of viral infections. Conclusions: Major burn injury results in immunosuppression and viral infection in a small number of patients. Recognition and antiviral therapy are employed, but additional studies are necessary to improve outcomes in these patients.
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Affiliation(s)
- John L Kiley
- Brooke Army Medical Center, Fort Sam Houston, Texas, USA
| | - Kevin K Chung
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Dana M Blyth
- Walter Reed National Military Medical Center, Bethesda, Maryland, USA
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48
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Abstract
Cytomegalovirus (CMV) reactivation has been described in adults with critical illness caused by diverse etiologies, especially severe sepsis, and observational studies have linked CMV reactivation with worse clinical outcomes in this setting. In this study, we review observational clinical data linking development of CMV reactivation with worse outcomes in patients in the intensive care unit, discuss potential biologically plausible mechanisms for a causal association, and summarize results of initial interventional trials that examined the effects of CMV prevention. These data, taken together, highlight the need for a randomized, placebo-controlled efficacy trial (1) to definitively determine whether prevention of CMV reactivation improves clinical outcomes of patients with critical illness and (2) to define the underlying mechanism(s).
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Affiliation(s)
- Hannah Imlay
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Ajit P Limaye
- Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington, USA
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Miglioli-Galvão L, Pestana JOM, Lopes-Santoro G, Torres Gonçalves R, Requião Moura LR, Pacheco Silva Á, Camera Pierrotti L, David Neto E, Santana Girão E, Costa de Oliveira CM, Saad Abboud C, Dias França JÍ, Devite Bittante C, Corrêa L, Aranha Camargo LF. Severe Strongyloides stercoralis infection in kidney transplant recipients: A multicenter case-control study. PLoS Negl Trop Dis 2020; 14:e0007998. [PMID: 32004346 PMCID: PMC7015428 DOI: 10.1371/journal.pntd.0007998] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 02/12/2020] [Accepted: 12/16/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Severe Strongyloides stercoralis infection in kidney transplant recipients is associated with considerable morbidity and mortality, although little is known about the risk factors for such infection. METHODOLOGY/PRINCIPAL FINDINGS This was a retrospective, multicenter, case-control study in which we assessed the risk factors for and clinical outcomes of severe S. stercoralis infections in kidney transplant recipients in Brazil. We included 138 kidney transplant recipients: 46 cases and 92 controls. Among the cases, the median number of days from transplantation to diagnosis was 117 (interquartile range [IQR], 73.5-965) and the most common clinical findings were gastrointestinal symptoms (in 78.3%) and respiratory symptoms (in 39.1%), whereas fever and eosinophilia were seen in only 32.6% and 43.5%, respectively. The 30-day all-cause mortality among the cases was 28.3% overall and was significantly higher among the cases of infection occurring within the first three months after transplantation (47% vs. 17.2%, P = 0.04). The independent risk factors were receiving a transplant from a deceased donor (odds ratio [OR] = 6.16, 95% confidence interval [CI] = 2.05-18.5), a history of bacterial infection (OR = 3.04, 95% CI = 1.2-7.5), and a cumulative corticosteroid dose (OR = 1.005, 95% CI = 1.001-1.009). The independent predictors of mortality were respiratory failure (OR = 98.33, 95% CI = 4.46-2169.77) and concomitant bacteremia (OR = 413.00, 95% CI = 4.83-35316.61). CONCLUSIONS/SIGNIFICANCE Severe S. stercoralis infections are associated with considerable morbidity and mortality after kidney transplantation. In endemic areas, such infection may occur late after transplantation, although it seems to be more severe when it occurs earlier after transplantation. Specific risk factors and clinical manifestations can identify patients at risk, who should receive prophylaxis or early treatment.
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Affiliation(s)
- Lísia Miglioli-Galvão
- Infectious Diseases Unit, Universidade Federal de São Paulo, São Paulo, Brazil
- * E-mail:
| | | | - Guilherme Lopes-Santoro
- Department of Preventive Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | - Álvaro Pacheco Silva
- Kidney Transplant Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
- Kidney Unit, Universidade Federal de São Paulo,São Paulo, Brazil
| | | | - Elias David Neto
- Kidney Transplant Unit, Universidade de São Paulo, São Paulo, Brazil
| | | | | | - Cely Saad Abboud
- Infectious Diseases Unit, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
| | - João Ítalo Dias França
- Department of Epidemiology and Statistics, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil
| | | | - Luci Corrêa
- Infectious Diseases Unit, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Luís Fernando Aranha Camargo
- Infectious Diseases Unit, Universidade Federal de São Paulo, São Paulo, Brazil
- Infectious Diseases Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil
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50
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Amaral PH, Ferreira BM, Roll S, Neves PD, Pivetta LG, Mohrbacher S, Dias ER, Sato VA, Oliveira ÉS, Pereira LV, Bales AM, Nardotto LL, Ferreira JN, Cuvello-Neto AL, Chocair PR. COVID-19 and Cytomegalovirus Co-infection: A Challenging Case of a Critically Ill Patient with Gastrointestinal Symptoms. Eur J Case Rep Intern Med 2020; 7:001911. [PMID: 33083369 PMCID: PMC7546567 DOI: 10.12890/2020_001911] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 07/30/2020] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED COVID-19 is a severe disease that has reached pandemic status. To the best of our knowledge, we describe the first case of COVID-19 and cytomegalovirus (CMV) co-infection in a critically ill patient. We discuss the challenge of establishing the diagnosis as well as the management of tissue-invasive gastrointestinal CMV infection (TI-GI CMV) simulating vascular involvement and intestinal obstruction in a critically ill patient. LEARNING POINTS We describe a case of COVID-19 and cytomegalovirus (CMV) co-infection in a critically ill patient.Clinical symptoms simulated mesenteric vascular involvement and intestinal obstruction.The successful management of invasive CMV colitis in a patient with COVID-19 with atypical symptoms is described.
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Affiliation(s)
- Pedro Hf Amaral
- Gastrointestinal Surgery Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazil
| | | | - Sergio Roll
- Gastrointestinal Surgery Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazil
| | - Precil Dmm Neves
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Luca Ga Pivetta
- Gastrointestinal Surgery Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazil
| | - Sara Mohrbacher
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Eduardo Rm Dias
- Gastrointestinal Surgery Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazil
| | - Victor Ah Sato
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Érico S Oliveira
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Leonardo Vb Pereira
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Alessandra M Bales
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Luciana L Nardotto
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | - Jéssica N Ferreira
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
| | | | - Pedro R Chocair
- Internal Medicine Service, Oswaldo Cruz German Hospital, São Paulo-SP, Brazi
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