First name
Ana
Middle name
María
Last name
Cárdenas

Title

Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes.

Year of Publication

2021

Date Published

2021 Apr 01

ISSN Number

2058-5276

Abstract

Respiratory syncytial virus (RSV) causes respiratory illness in children, immunosuppressed individuals and the elderly. However, the viral factors influencing the clinical outcome of RSV infections remain poorly defined. Defective viral genomes (DVGs) can suppress virus replication by competing for viral proteins and by stimulating antiviral immunity. We studied the association between detection of DVGs of the copy-back type and disease severity in three RSV A-confirmed cohorts. In hospitalized children, detection of DVGs in respiratory samples at or around the time of admission associated strongly with more severe disease, higher viral load and a stronger pro-inflammatory response. Interestingly, in experimentally infected adults, the presence of DVGs in respiratory secretions differentially associated with RSV disease severity depending on when DVGs were detected. Detection of DVGs early after infection associated with low viral loads and mild disease, whereas detection of DVGs late after infection, especially if DVGs were present for prolonged periods, associated with high viral loads and severe disease. Taken together, we demonstrate that the kinetics of DVG accumulation and duration could predict clinical outcome of RSV A infection in humans, and thus could be used as a prognostic tool to identify patients at risk of worse clinical disease.

DOI

10.1038/s41564-021-00882-3

Alternate Title

Nat Microbiol

PMID

33795879

Title

Outcomes of human adenovirus infection and disease in a retrospective cohort of pediatric solid organ transplant recipients.

Year of Publication

2019

Number of Pages

e13510

Date Published

2019 Jun 18

ISSN Number

1399-3046

Abstract

<p>Information about HAdV infection in SOT recipients is limited. We aimed to describe HAdV infection epidemiology and outcomes in a single-center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004-2013 were followed up for 180&nbsp;days post-transplant. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ-specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV infection was defined as HAdV disease or ≥1-log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty-four (10.6%) had ≥1 HAdV-positive PCR. HAdV-positive subjects were younger than uninfected subjects (2.0&nbsp;years vs 6.5, P&nbsp;=&nbsp;0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV infection. All-cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV infection was infrequently detected in SOT recipients. Over one-third of HAdV-positive patients met disease criteria at detection or had infection progression, but none died. This low all-cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.</p>

DOI

10.1111/petr.13510

Alternate Title

Pediatr Transplant

PMID

31210395

Title

Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients.

Year of Publication

2018

Date Published

2018 Jun 08

ISSN Number

2048-7207

Abstract

<p><strong>Background: </strong>Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir.</p>

<p><strong>Methods: </strong>A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection.</p>

<p><strong>Results: </strong>Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of &lt;200 cells/μL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]).</p>

<p><strong>Conclusions: </strong>HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.</p>

DOI

10.1093/jpids/piy049

Alternate Title

J Pediatric Infect Dis Soc

PMID

29893957

Title

Implementation of a rapid influenza A/B and RSV direct molecular assay improves emergency department oseltamivir use in paediatric patients.

Year of Publication

2018

Number of Pages

358-363

Date Published

2018 Mar

ISSN Number

1473-5644

Abstract

<p><strong>PURPOSE: </strong>Influenza A virus (FluA), influenza B virus (FluB) and respiratory syncytial virus (RSV) illnesses increase hospitalizations during seasonal epidemics.</p>

<p><strong>METHODOLOGY: </strong>To determine the utility of the Simplexa FluA/B &amp; RSV Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this assay to emergency department (ED) patients with influenza-like illness.</p>

<p><strong>RESULTS: </strong>Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours. Compared to the flu season prior to implementation of the Direct Flu/RSV, clinicians were more likely to prescribe 5 days of oseltamivir therapy for Direct Flu/RSV-positive patients in comparison to those with a negative test.</p>

<p><strong>CONCLUSIONS: </strong>Use of Direct Flu/RSV provides results rapidly, which leads to more appropriate use of oseltamivir. The ease of use of this assay and quick TAT allows for prompt decision-making, which is essential for patient care and effective disease control during the influenza season.</p>

DOI

10.1099/jmm.0.000676

Alternate Title

J. Med. Microbiol.

PMID

29458688

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