Approaches and Challenges in the Current Management of Cytomegalovirus in Transplant Recipients: Highlighting the Role of Advanced Practice Providers (Nurse Practitioners and Physician Assistants).

Cytomegalovirus (CMV) infection is associated with increased morbidity and mortality in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients, with traditional anti-CMV therapies limited by their associated toxicities and the development of resistance. Clinical providers are often faced with challenging and complicated CMV infections that require multiple courses of antiviral therapies. Increasingly, advanced practice providers (APPs) are playing an important role in the day-to-day management of transplant recipients with CMV infection, including resistant/refractory CMV and other complex CMV syndromes. Here, we provide an overview of current preventative and treatment strategies for CMV infection in HCT and SOT recipients, highlighting the challenging aspects of current management and the potential utility of newer antiviral agents. This article also focuses on how a multidisciplinary team, orchestrated by APPs, can improve CMV-associated patient outcomes. Protocols using antiviral agents for the prevention or treatment of CMV infections require carefully designed and meticulously implemented strategies to ensure the best clinical outcomes for patients. APPs, who have increasingly become the frontline providers of outpatient care for transplant recipients, are ideally positioned to design and carry out these protocols.

Immunogenicity of SARS-CoV-2 vaccines in patients with multiple myeloma: a systematic review and meta-analysis.

Patients with multiple myeloma (MM) have a diminished immune response to coronavirus disease 2019 (COVID-19) vaccines. Risk factors for an impaired immune response are yet to be determined. We aimed to summarize the COVID-19 vaccine immunogenicity and to identify factors that influence the humoral immune response in patients with MM. Two reviewers independently conducted a literature search in MEDLINE, Embase, ISI Web of Science, Cochrane library, and Clinicaltrials.gov from existence until 24 May 24 2022. (PROSPERO: CRD42021277005). A total of 15 studies were included in the systematic review and 5 were included in the meta-analysis. The average rate (range) of positive functional T-lymphocyte response was 44.2% (34.2%-48.5%) after 2 doses of messenger RNA (mRNA) COVID-19 vaccines. The average antispike antibody response rates (range) were 42.7% (20.8%-88.5%) and 78.2% (55.8%-94.2%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. The average neutralizing antibody response rates (range) were 25% (1 study) and 62.7% (53.3%-68.6%) after 1 and 2 doses of mRNA COVID-19 vaccines, respectively. Patients with high-risk cytogenetics or receiving anti-CD38 therapy were less likely to have a humoral immune response with pooled odds ratios of 0.36 (95% confidence interval [95% CI], 0.18, 0.69), I2 = 0% and 0.42 (95% CI, 0.22, 0.79), I2 = 14%, respectively. Patients who were not on active MM treatment were more likely to respond with pooled odds ratio of 2.42 (95% CI, 1.10, 5.33), I2 = 7%. Patients with MM had low rates of humoral and cellular immune responses to the mRNA COVID-19 vaccines. Further studies are needed to determine the optimal doses of vaccines and evaluate the use of monoclonal antibodies for pre-exposure prophylaxis in this population.

Combination Therapy With Casirivimab/Imdevimab and Remdesivir for Protracted SARS-CoV-2 Infection in B-cell-Depleted Patients.

Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir.

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis.

BACKGROUND: In allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients, the inter-relationship between post-transplant cytomegalovirus (CMV) and subsequent invasive fungal infections (IFIs) is conflicting and the association of CMV serostatus with IFIs has not been evaluated. OBJECTIVES: To determine the relationship between CMV infection/serostatus and IFIs in allo-HSCT populations. DATA SOURCES: A systematic literature search was conducted from existence until 11 July 2021 using Medline, Embase and ISI Web of Science databases. STUDY ELIGIBILITY CRITERIA: Cross-sectional, prospective cohort, retrospective cohort and case-control studies that reported allo-HSCT recipients with CMV and without CMV who developed or did not develop IFIs after CMV infection. PARTICIPANTS: Allo-HSCT recipients. INTERVENTIONS: Not applicable. METHODS: A systematic search, screening, data extracting and assessing study quality were independently conducted by two reviewers. The Newcastle-Ottawa scale was used to assess risk of bias. data were analysed using the pooled effect estimates of a random-effects model. RESULTS: A total of 18 and 12 studies were included for systematic review and meta-analysis, respectively. Post-transplant CMV infection significantly increased the risk of IFIs with a pooled hazard ratio (pHR) of 2.58 (1.78, 3.74), I2 = 75%. Further subgroup analyses by timing of IFIs, CMV definitions, study continents, study design and adjustment of effect estimates showed that post-transplant CMV infection consistently increased the risk of subsequent IFIs. High-risk CMV serostatus (D-/R+) increased the risk of IFIs with a pooled odds ratio (OR) of 1.33 (1.04, 1.71), I2 = 0%, but low-risk CMV serostatus (D-/R-) decreased the risk of IFIs with a pOR of 0.69 (0.55, 0.87), I2 = 0%. CONCLUSIONS: Post-transplant CMV infection and high-risk CMV serostatus increased the risk of IFIs, but low-risk CMV serostatus decreased risk of IFIs among allo-HSCT recipients. Further studies are needed to identify at-risk allo-HSCT recipients as well as to focus on fungal diagnostics and prophylaxis to prevent this fungal-after-viral phenomenon.

Comparison of Standardized Cytomegalovirus (CMV) Viral Load Thresholds in Whole Blood and Plasma of Solid Organ and Hematopoietic Stem Cell Transplant Recipients with CMV Infection and Disease.

BACKGROUND: Quantification of cytomegalovirus (CMV) deoxyribonucleic acid (DNA) has important diagnostic, prognostic, and therapeutic implications in the management of transplant recipients. We aimed to assess a viral load in plasma and whole blood that distinguishes CMV disease from asymptomatic infection in a cohort of solid organ and hematopoietic stem cell transplantation. METHODS: We prospectively measured and compared CMV viral load in paired plasma and whole blood samples collected from transplant recipients with CMV infection and disease. Cytomegalovirus viral loads were determined by a commercially available US Food and Drug Administration-approved quantitative assay (COBAS AmpliPrep/COBAS TaqMan CMV Test [CAP/CTM CMV]) calibrated to the first World Health Organization International Standard for CMV DNA quantification. RESULTS: Moderate agreement of CMV viral load was observed between plasma and whole blood, with 31% of samples having discordant findings, particularly among samples with low DNA levels. Among the subset of samples where both paired samples had quantifiable levels, we observed a systematic bias that reflected higher viral load in whole blood compared with plasma. Based on receiver operating curve analysis, an initial plasma CMV viral load threshold of 1700 IU/mL in solid organ transplant recipients (sensitivity 80%, specificity 74%) and 1350 IU/mL in allogeneic hematopoietic stem cell transplant recipients (sensitivity 87%, specificity 87%) distinguished CMV disease and asymptomatic infection. CONCLUSIONS: This study identifies standardized viral load thresholds that distinguish CMV disease from asymptomatic infection using CAP/CTM CMV assay. We propose these thresholds as potential triggers to be evaluated in prospective studies of preemptive therapy. Plasma was better than whole blood for measuring viral load using the CAP/CTM CMV assay.

Cytomegalovirus.

Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised hosts. Laboratory methods for diagnosis include molecular testing, antigenemia, culture, serology, and histopathology. Treatment of CMV infection and disease is indicated in selected immunocompromised hosts, and preventive approaches are indicated in high-risk groups. This chapter reviews the epidemiology, clinical aspects, and the laboratory diagnosis and management of CMV in immunocompromised hosts.

Use of Extracorporeal Membrane Oxygenation for the Treatment of Influenza-Induced Acute Respiratory Distress Syndrome in Immunocompromised Adults.

Influenza infection in the adult immunocompromised hosts can have severe presentations and rapid progression to lower respiratory tract infection requiring mechanical ventilation, and it even can progress to acute respiratory distress syndrome. Little is known about the role of extracorporeal membrane oxygenation for management in this setting. We present a review of the current literature on the subject.

Treatment of cytomegalovirus infection and disease pre- and post-quantitative nucleic acid test standardization: does use of a more sensitive assay lead to longer treatment duration?

Quantitative cytomegalovirus (CMV) nucleic acid testing (NAT) has been standardized using the World Health Organization (WHO) international calibration standard. A new FDA-approved WHO-calibrated assay (CA) was found to be more sensitive than a laboratory-developed test (LDT). We hypothesized that monitoring therapeutic response using a more sensitive assay may lead to longer antiviral therapy in solid organ and hematopoietic stem cell transplant patients with CMV infection. We reviewed transplant patients with CMV disease retrospectively, and divided them into two groups: those diagnosed and managed based on LDT and those managed using WHO-CA. Compared to patients monitored by LDT, the time to reach an undetectable viral load was significantly longer in the group monitored by the WHO-CA. However, a trend toward shorter duration of antiviral treatment was observed (median, 34 vs. 41 d; p = 0.058), with earlier discontinuation of induction antiviral therapy upon reaching undetectable viral load using WHO-CA (11 vs. 18 d; p = 002). We concluded that despite using a more sensitive CMV NAT, the total duration of antiviral treatment was not significantly prolonged in transplant patients with CMV infection and disease. Relapse rates did not differ between the two groups.

Gastrointestinal mucormycosis in immunocompromised hosts.

Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non-specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.