Does Detection of Respiratory Viral Infection in Upper Respiratory Tract (URT) Predict Lower Respiratory Tract (LRT) Disease in Hematopoietic Cell Transplant (HCT) Patients?

Abstract Background HCT recipients are frequently infected with respiratory viruses (RVs) in the URT; however, diagnostic evaluation of the LRT by bronchoalveolar lavage (BAL) is less common. We sought to determine whether the detection of RVs in the URT is predictive of LRT detection and to identify factors that predict discordance between upper and lower RV detection. Methods HCT recipients with respiratory symptoms and LRT RV testing via multiplex PCR in BAL from July 2009 to October 2016 were included in the study. RV PCR results, including cycle threshold (CT) values, were compared with URT samples obtained within ±3 days. Logistic regression models were used to analyze risk factors for RV discordance between paired samples. Results Among 1,000 HCT recipients with BAL RV testing, 250 had URT testing within 3 days. In total, 75(30%) sample pairs were concordant for the same RV in both the URT and BAL (P/P); 132 (53%) were negative from both sites. Among 43 discordant pairs, 25 (10%) were only positive by URT but negative by BAL (P/N) and 18 (7%) were positive by BAL but negative by URT (N/P). In pairs with positive RV results in the URT or BAL, discordance was common for HMPV (44%), HRV (33%), and PIV-3 (28%); RSV was almost always concordant (92%) (Figure 1). In a multivariable model, the risk of discordance (P/N or N/P) was increased in the presence of a solitary nodule on radiography (OR 6.8; 95% CI 1.2–38.3) and with lymphocyte count >500/mm3 (OR 3.1; 95% CI 1.08–9.0). Among P/P pairs, the median difference between CT values between URT and BAL samples was 0 (range −12 to +13), with 33 and 29% of subjects having lower and higher CT values (>4, ~1 log10) in the BAL, respectively (Figure 2). Conclusion In symptomatic HCT recipients with RV PCR testing performed concurrently in the upper and lower tract, discordant results are relatively common, especially for HRV, HMPV, and PIV-3. The presence of a solitary nodule on imaging and the absence of lymphopenia are associated with discordant results, with BAL results more likely being negative in these situations. More than half of the P/P pairs had a >4 difference in CT values between URT and LRT samples. Taken together, these data suggest that RV testing in BAL can provide useful diagnostic information that may guide management in HCT recipients. Disclosure S. A. Pergam, MERCK: Consultant and Investigator, Consulting fee.

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Predictive Value of Respiratory Viral Detection in the Upper Respiratory Tract for Infection of the Lower Respiratory Tract With Hematopoietic Stem Cell Transplantation

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz470 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jim Boonyaratanakornkit ◽

Meghana Vivek ◽

Hu Xie ◽

Steven A Pergam ◽

Guang-Shing Cheng ◽

...

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Upper Respiratory Tract ◽

Hematopoietic Cell Transplant ◽

Hematopoietic Stem ◽

Logistic Regression Models ◽

Upper Respiratory ◽

Syncytial Virus

Abstract Background Hematopoietic cell transplant (HCT) recipients are frequently infected with respiratory viruses (RVs) in the upper respiratory tract (URT), but the concordance between URT and lower respiratory tract (LRT) RV detection is not well characterized. Methods Hematopoietic cell transplant candidates and recipients with respiratory symptoms and LRT and URT RV testing via multiplex PCR from 2009 to 2016 were included. Logistic regression models were used to analyze risk factors for LRT RV detection. Results Two-hundred thirty-five HCT candidates or recipients had URT and LRT RV testing within 3 days. Among 115 subjects (49%) positive for a RV, 37% (42 of 115) had discordant sample pairs. Forty percent (17 of 42) of discordant pairs were positive in the LRT but negative in the URT. Discordance was common for adenovirus (100%), metapneumovirus (44%), rhinovirus (34%), and parainfluenza virus type 3 (28%); respiratory syncytial virus was highly concordant (92%). Likelihood of LRT detection was increased with URT detection (oods ratio [OR] = 73.7; 95% confidence interval [CI], 26.7–204) and in cytomegalovirus-positive recipients (OR = 3.70; 95% CI, 1.30–10.0). Conclusions High rates of discordance were observed for certain RVs. Bronchoalveolar lavage sampling may provide useful diagnostic information to guide management in symptomatic HCT candidates and recipients.

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A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients

Clinical Infectious Diseases ◽

10.1093/cid/ciz1166 ◽

2019 ◽

Vol 71 (11) ◽

pp. 2777-2786 ◽

Cited By ~ 14

Author(s):

Roy F Chemaly ◽

Sanjeet S Dadwal ◽

Anne Bergeron ◽

Per Ljungman ◽

Yae-Jean Kim ◽

...

Keyword(s):

Viral Load ◽

Respiratory Tract ◽

Weighted Average ◽

Cell Transplant ◽

Upper Respiratory Tract ◽

Hematopoietic Cell Transplant ◽

Double Blind ◽

Time Weighted Average ◽

Upper Respiratory ◽

Syncytial Virus

Abstract Background Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. Methods Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. Results From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22–1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. Conclusions Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. Clinical Trials Registration NCT02254408; EUDRA-CT#2014-002474-36.

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1583. The Utility of the Immunodeficiency Scoring Index (ISI) to Predict Outcomes of Coronavirus (HCoV) Infections in Hematopietic Cell Transplant (HCT) Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1411 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S495-S495

Author(s):

Fareed Khawaja ◽

Terri Lynn Shigle ◽

Shashank S Ghantoji ◽

Marjorie Batista ◽

Ella Ariza-Heredia ◽

...

Keyword(s):

Mechanical Ventilation ◽

Respiratory Tract ◽

Viral Infections ◽

Fatal Outcome ◽

High Morbidity ◽

Cell Transplant ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Tract Infections ◽

Overall Mortality

Abstract Background Respiratory viral infections in HCT recipients are associated with high morbidity and mortality, especially after progression from upper respiratory tract infection (URI) to lower respiratory tract infections (LRI). Data on risk factors (RF) for LRI and mortality is lacking for HCoV infections after HCT. We aimed to validate our ISI in HCoV infections. Methods All adult HCT recipients with HCoV infection from 2015 to 2017 were evaluated. An ISI based on RF was used to classify patients as low (0–2), moderate (3–6), or high (7 or higher) risk for progression to LRI or death. We defined LRI as HCoV detected in nasal wash and/or bronchoalveolar lavage and new lung infiltrates on diagnostic imaging. Clinical parameters were collected and ISI were calculated for comparison. Results A total of 144 adult HCT recipients with 166 episodes of HCoV infections were analyzed. The most common HCoV serotype for LRI and URI was 229E (42.4%) and OC43 (37.6%), respectively, and most patients were infected between November and March each year (Figures 1 and 2). When compared with URI, patients with LRI were more likely in the pre-engraftment period, had multiple respiratory viruses infections, had nosocomially acquired HCoV, required hospitalization, ICU transfer, and mechanical ventilation (all, P < 0.05). Overall mortality rate was 4% at Day 30 from diagnosis and all patients who died had LRI with an 18% mortality. Among those who died, 33% had nosocomial infection, 67% were co-infected with another respiratory virus and 67% required mechanical ventilation. Using an ISI cut off of <4, the negative predictive value (NPV) for progression to LRI was 86% with a specificity of 76%. Conclusion HCT recipients with HCoV LRI were more likely to have a fatal outcome. The NPV of the ISI for progression to LRI was high and could be used as a prognostic tool for future studies and for therapeutic clinical trials. Disclosures All authors: No reported disclosures.

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Epidemiology and Outcomes of Respiratory Virus Infections in Adult Acute Leukemia and Hematopoietic Stem Cell Transplant Patients

Blood ◽

10.1182/blood.v124.21.4984.4984 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4984-4984

Author(s):

Gaurav Trikha ◽

Rebecca Conway ◽

John W Hiemenz ◽

Per T. Ljungman

Keyword(s):

Respiratory Tract ◽

Acute Leukemia ◽

Multiplex Pcr ◽

Respiratory Virus ◽

Cell Transplant ◽

Upper Respiratory Tract ◽

Virus Infections ◽

Hematopoietic Stem ◽

Upper Respiratory ◽

Respiratory Virus Infections

Abstract BACKGROUND Respiratory virus infections (RVI) are significant cause of morbidity and mortality in adult patients with hematopoietic stem cell transplant (HSCT) recipients, causing delay in administering chemotherapy and HSCT, increased hospital stay and in occasionally resulting in mortality. In 2008, the FDA approved the use of multiplex PCR assay to detect respiratory viruses. Our institution has been using the multiplex PCR technique for approximately four years. With this technology the time to diagnosis of a RVI became shorter and detection of multiple viruses at the same time became feasible. RVIs have been studied more exclusively in the HSCT population where lymphopenia has been identified for poor outcomes. These infections have been less well studied in the acute leukemia population. This report, however, encompasses both patient populations. The natural progression of RVIs apart from influenza is poorly understood. The viruses isolated from the upper respiratory tract, development of lower respiratory tract infection (LRI), as well as overall survival of the patients identified with RVIs are reported here. STUDY DESIGN This is a retrospective cohort study of adult patients (>=18yrs) with acute leukemia and/or after HSCT diagnosed with laboratory documented RVI between May 1st 2010 and March 1st2014. A list of positive RVIs from multiplex PCR was retrieved from the hospital laboratory based on patients with specific ICD-9 codes. RESULTS Between May 2010 to March 2014, there were 208 episodes of RVI in 122 patients. Out of these, 77 patients were post-HSCT and 45 patients had acute leukemia without undergoing HSCT. Out of these episodes, 85 were caused by rhinovirus, 37 by coronavirus, 18 by RSV, 35 by parainfluenza, 15 by influenza, 12 by metapneumovirus, 3 by adenovirus, 3 by poly-viral infection. 189 episodes were initially diagnosed as an upper respiratory tract infection (URI). There were 47 episodes of LRI; of these 32 (16.9%) had a prior URI with rhinovirus (n=13), coronavirus (n=5), parainfluenza (n=4), RSV (n=4), influenza (n=3) and poly-viral infections (n=2). 15 (7.2%) episodes were LRI at initial presentation (4 metapneumovirus, 4 parainfluenza, 2 RSV, 3 rhinovirus, 1 coronavirus, 1 adenovirus). Out of the 122 patients there were 7 deaths (5.7%). CONCLUSION The availability of multiplex PCR has allowed for the identification of respiratory viruses responsible for URI in this patient population. Most of these infections have limited clinical consequences. However, in our study 25% of the episodes either presented with or progressed to LRI. The exact role of respiratory virus in causing LRI is difficult to determine in a retrospective study. Disclosures Off Label Use: Treating MDS with one of these regimens: (1) nelfinavir, (2) bortezomib, (3) metformin + simvastatin, (4) metformin + seliciclib, (5) nelfinavir + bortezomib, (6) nelfinavir + ruxolitinib, (7) nelfinavir + simvastatin, (8) nelfinavir + sorafenib, (9) nelfinavir + trametinib, (10) ponatinib + bortezomib, (11) nelfinavir + ponatinib, and (12) trametinib + simvastatin.

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