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Viruses
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Viral Infections in Immunocompromised Hosts
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Viral Infections in Immunocompromised Hosts

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 8495

Special Issue Editors

Dr. Dora Ho

E-Mail Website
Guest Editor
Division of Infectious Diseases & Geographic Medicine, School of Medicine, Stanford University, Stanford, CA, USA
Interests: immunocompromised hosts; transplant; cancer; viral infections; fungal infections
Dr. Ralph Tayyar

E-Mail Website
Co-Guest Editor
Division of Allergy & Infectious Diseases, University of Washington, Seattle, WA, USA
Interests: immunocompromised infectious diseases; transplant; antimicrobial stewardship; viral infections; fungal infections

Special Issue Information

Dear Colleagues,

Immunocompromised hosts, including those with stem cell transplantation, solid organ transplantation, malignancies, or inborn/iatrogenic immunodeficiencies, are at increased risk for infectious complications. Among various groups of pathogens, viruses continue to cause significant morbidities and mortalities in immunocompromised patients despite recent advances in diagnostic and treatment modalities for viral infections. From herpesviruses, respiratory viruses, and polyomaviruses to viruses that cause diarrheal syndromes, therapeutic options remain limited either due to low efficacy, undesirable toxicity profile, or both. Distinguishing between “benign” viral reactivation and clinically significant viral disease is another major challenge for physicians that care for such immunocompromised patients.

To provide a forum of expert opinions and showcase the latest developments in this field, this Special Issue of Viruses is devoted to “Viral Infections in the Immunocompromised Hosts”. We welcome submission of reviews and original research articles for this Special Issue focusing on the diagnostics, management, and treatment of viral infections in immunocompromised hosts. Discussion on the immunology aspect of viral infections is also welcome.

Dr. Dora Ho
Dr. Ralph Tayyar
Guest Editors

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Keywords

  • viral infections
  • herpesviruses
  • respiratory viruses
  • polyomaviruses
  • viral diarrheal syndromes
  • immunocompromised hosts
  • transplant infectious diseases

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Published Papers (7 papers)

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Research

Jump to: Review

9 pages, 657 KiB  
Article
Real-World Comparison of Maribavir to Foscarnet for the Treatment of Cytomegalovirus in Solid Organ and Hematopoietic Stem Cell Transplant Recipients
by Lauren Ogawa, Chelsea Morinishi, Ashrit Multani, Pryce Gaynor, Omer E. Beaird, Christine Pham and Joanna M. Schaenman
Viruses 2024, 16(12), 1889; https://doi.org/10.3390/v16121889 - 7 Dec 2024
Viewed by 653
Abstract
Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option [...] Read more.
Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection. This was a single-center retrospective study of clinical outcomes of patients who received MBV compared to a control group who received FOS for an episode of CMV infection. Each cohort consisted of 27 episodes of CMV infection. Twenty patients in the MBV cohort and from the FOS cohort cleared the infection, with five and three patients developing MBV or FOS resistance, respectively. There were no statistically significant differences in failure of therapy as evidenced by persistent DNAemia (p = 0.56) or development of antiviral resistance (p = 0.24). In conclusion, MBV was as effective as FOS for the treatment of R/R CMV infection and was better tolerated without increased risk of antiviral resistance. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
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15 pages, 1539 KiB  
Article
The Association Between Cytomegalovirus Infection and Kidney Damage in the Liver Transplant Setting
by Ramin Raul Ossami Saidy, Franziska Eurich, Brigitta Globke, Wenzel Schöning, Robert Öllinger, Nathanael Raschzok, Johann Pratschke, Dennis Eurich, Luca Dittrich and Eva Maria Dobrindt
Viruses 2024, 16(12), 1830; https://doi.org/10.3390/v16121830 - 26 Nov 2024
Viewed by 580
Abstract
Introduction: The development of chronic kidney disease (CKD) is a common and significant complication, contributing to morbidity after liver transplantation (LT). Cytomegalovirus (CMV) infection is common in the overall population, and relevant reinfection after LT may occur. CMV-associated kidney damage has been discussed, [...] Read more.
Introduction: The development of chronic kidney disease (CKD) is a common and significant complication, contributing to morbidity after liver transplantation (LT). Cytomegalovirus (CMV) infection is common in the overall population, and relevant reinfection after LT may occur. CMV-associated kidney damage has been discussed, but the clinical significance on CKD development after LT remains unclear. Methods: A total of 745 patients who underwent LT between 2006 and 2017 were included in this retrospective analysis. Clinical data, as well as laboratory parameters, were analyzed. Univariate and multivariate analysis were performed. Results: The univariate analysis revealed significantly impaired estimated glomerular filtration rates (eGFRs) in patients with histories of CMV infection (81.4 (8–137) mL/min vs. 90.0 (5–147) mL/min; p = 0.004). This effect was confirmed in the multivariate analysis. Post-LT, eGFR was impaired in patients with CMV (re)infection at 6, 12, 36, and 60 months, 10 years, and 15 years after LT. Immunosuppressive levels were comparable between groups. Overall survival was negatively affected by CMV infection (p = 0.001). Discussion: A clinically significant detrimental impact of CMV infection on renal function was observed, that could individualize clinical risk evaluation prior and after LT further. However, the pathophysiological mechanisms behind this observation are not yet understood. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
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10 pages, 1347 KiB  
Article
Association between Respiratory Virus Infection and Development of De Novo Donor-Specific Antibody in Lung Transplant Recipients
by Anoma Nellore, Julie Houp, John T. Killian, Ajit P. Limaye and Cynthia E. Fisher
Viruses 2024, 16(10), 1574; https://doi.org/10.3390/v16101574 - 5 Oct 2024
Viewed by 955
Abstract
Chronic lung allograft dysfunction (CLAD) is the most common cause of long-term lung allograft failure. Several factors, including respiratory virus infection (RVI), have been associated with CLAD development, but the underlying mechanisms of these associations are not well understood. We hypothesize that RVI [...] Read more.
Chronic lung allograft dysfunction (CLAD) is the most common cause of long-term lung allograft failure. Several factors, including respiratory virus infection (RVI), have been associated with CLAD development, but the underlying mechanisms of these associations are not well understood. We hypothesize that RVI in lung transplant recipients elicits the development of donor-specific antibodies (DSAs), thus providing a mechanistic link between RVI and CLAD development. To test this hypothesis, we retrospectively evaluated for the presence of HLA antibodies in a cohort of lung transplant recipients with symptomatic RVI within the first four months post-transplant using sera at two time points (at/directly after the transplant and following RVI) and time-matched controls without RVI (post-transplant). We found a trend toward the development of de novo DSAs in those with symptomatic RVI versus controls [6/21 (29%) vs. 1/21 (5%), respectively, p = 0.09]. No cases or controls had DSA at baseline. We also found increased rates of CLAD and death among those who developed class II DSA versus those who did not (CLAD: 5/7 (71.4%) vs. 19/34 (54.3%), death: 5/7 (71.4%) vs. 17/35 (48.6%)). Prospective studies evaluating the temporal development of DSA after RVI in lung transplant patients and the subsequent outcomes are warranted. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
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24 pages, 5701 KiB  
Article
Cytokine Dynamics and Herpesvirus Interactions in Pediatric Liver and Kidney Transplant Recipients: The Distinct Behavior of HCMV, HHV6, HHV7 and EBV
by Yessica Sánchez-Ponce, Juan Rafael Murillo-Eliosa, Abigail Morales-Sanchez and Ezequiel M. Fuentes-Pananá
Viruses 2024, 16(7), 1067; https://doi.org/10.3390/v16071067 - 2 Jul 2024
Viewed by 2399
Abstract
Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein–Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) [...] Read more.
Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein–Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with β-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
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Review

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16 pages, 271 KiB  
Review
Antiviral Stewardship in Transplantation
by Sruthi Bonda, Sonya Trinh and Jonathan Hand
Viruses 2024, 16(12), 1884; https://doi.org/10.3390/v16121884 - 5 Dec 2024
Viewed by 580
Abstract
Though antimicrobial stewardship programs (ASPs) are required for hospitals, the involvement of transplant recipients in programmatic interventions, protocols, and metrics has historically been limited. Though there is a growing interest in studying stewardship practices in transplant patients, optimal practices have not been clearly [...] Read more.
Though antimicrobial stewardship programs (ASPs) are required for hospitals, the involvement of transplant recipients in programmatic interventions, protocols, and metrics has historically been limited. Though there is a growing interest in studying stewardship practices in transplant patients, optimal practices have not been clearly established. A component of ASPs, antiviral stewardship (AVS), specifically targeting cytomegalovirus (CMV), has been more recently described. Understanding AVS opportunities and interventions is particularly important for transplant recipients, given the morbidity and mortality associated with viral infections, challenging clinical syndromes, ultrasensitive molecular diagnostic assays, antiviral resistance, and costs of viral disease and medications, as well as antiviral drug toxicities. This review highlights opportunities for AVS for CMV, EBV, HSV, VZV, SARS-CoV-2, respiratory syncytial virus, and BK polyomavirus in transplant patients. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
13 pages, 1012 KiB  
Review
Cytomegalovirus Infection After Solid Organ Transplantation: How I Use Cell-Mediated Immune Assays for Management
by Raymund R. Razonable
Viruses 2024, 16(11), 1781; https://doi.org/10.3390/v16111781 - 15 Nov 2024
Viewed by 1128
Abstract
Introduction: The pathogenesis and outcome of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) reflects the interplay between viral replication and CMV-specific immunity. Despite advances in its diagnosis and treatment, CMV continues to cause significant morbidity after SOT. Since CMV is an opportunistic [...] Read more.
Introduction: The pathogenesis and outcome of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) reflects the interplay between viral replication and CMV-specific immunity. Despite advances in its diagnosis and treatment, CMV continues to cause significant morbidity after SOT. Since CMV is an opportunistic pathogen that occurs as a result of impaired pathogen-specific immunity, laboratory assays that measure CMV-specific immune responses may be useful in assisting clinicians in its management. Methods and Results: The author summarizes the evolving and emerging data on the clinical utility of assays that quantify cell-mediated immune responses to CMV in SOT recipients. The majority of publications are observational studies that demonstrate that a lack or deficiency in CMV-specific cell-mediated immunity is correlated with a heightened risk of primary, reactivation, or recurrent CMV after transplantation. A few prospective interventional studies have utilized CMV-specific cell-mediated immune assays in guiding the duration of antiviral prophylaxis among CMV-seropositive SOT recipients. Likewise, CMV-specific cell-mediated immunity assays have been suggested to inform the need for secondary antiviral prophylaxis and immunologic optimization to prevent CMV relapse after treatment. Conclusions: CMV-specific cell-mediated immune assays are emerging to assist transplant clinicians in predicting a patient’s risk of CMV after transplantation, and these assays have been utilized to individualize the approach to CMV prevention and treatment. The author suggests the conduct of more interventional studies to further solidify the role of CMV-specific cell-mediated immune assays in routine clinical practice. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
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26 pages, 444 KiB  
Review
Arbovirus in Solid Organ Transplants: A Narrative Review of the Literature
by Kiran Gajurel, Reshika Dhakal and Stan Deresinski
Viruses 2024, 16(11), 1778; https://doi.org/10.3390/v16111778 - 15 Nov 2024
Viewed by 1061
Abstract
The incidence of arbovirus infections has increased in recent decades. Other than dengue, chikungunya, and West Nile viruses, the data on arbovirus in solid organ transplant (SOT) are limited to case reports, and infections in renal transplant recipients account for most of the [...] Read more.
The incidence of arbovirus infections has increased in recent decades. Other than dengue, chikungunya, and West Nile viruses, the data on arbovirus in solid organ transplant (SOT) are limited to case reports, and infections in renal transplant recipients account for most of the reported cases. Dengue and West Nile infections seem to be more severe with higher mortality in SOT patients than in the general population. Acute kidney injury is more frequent in patients with dengue and chikungunya although persistent arthralgia with the latter is less frequent. There is no clear relationship between arboviral infection and acute cellular rejection. Pre-transplant screening of donors should be implemented during increased arboviral activity but, despite donor screening and negative donor nucleic acid amplification test (NAT), donor derived infection can occur. NAT may be transiently positive. IgM tests lack specificity, and neutralizing antibody assays are more specific but not readily available. Other tests, such as immunohistochemistry, antigen tests, PCR, metagenomic assays, and viral culture, can also be performed. There are a few vaccines available against some arboviruses, but live vaccines should be avoided. Treatment is largely supportive. More data on arboviral infection in SOT are needed to understand its epidemiology and clinical course. Full article
(This article belongs to the Special Issue Viral Infections in Immunocompromised Hosts)
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