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  • 1
    Online Resource
    Online Resource
    Temporal Dysbiosis of Infant Nasal Microbiota Relative to Respiratory Syncytial Virus Infection
    Oxford University Press (OUP) ; 2021
    In:  The Journal of Infectious Diseases Vol. 223, No. 9 ( 2021-05-20), p. 1650-1658
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 223, No. 9 ( 2021-05-20), p. 1650-1658
    Abstract: Respiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Infant airway microbiota has been associated with respiratory disease risk and severity. The extent to which interactions between RSV and microbiota occur in the airway, and their impact on respiratory disease susceptibility and severity, are unknown. Methods We carried out 16S rRNA microbiota profiling of infants in the first year of life from (1) a cross-sectional cohort of 89 RSV-infected infants sampled during illness and 102 matched healthy controls, and (2) a matched longitudinal cohort of 12 infants who developed RSV infection and 12 who did not, sampled before, during, and after infection. Results We identified 12 taxa significantly associated with RSV infection. All 12 taxa were differentially abundant during infection, with 8 associated with disease severity. Nasal microbiota composition was more discriminative of healthy vs infected than of disease severity. Conclusions Our findings elucidate the chronology of nasal microbiota dysbiosis and suggest an altered developmental trajectory associated with RSV infection. Microbial temporal dynamics reveal indicators of disease risk, correlates of illness and severity, and impact of RSV infection on microbiota composition.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiaa577
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-blind, randomised, placebo-controlled, phase 3 trial
    Elsevier BV ; 2021
    In:  The Lancet Respiratory Medicine Vol. 9, No. 12 ( 2021-12), p. 1365-1376
    Details
    In: The Lancet Respiratory Medicine, Elsevier BV, Vol. 9, No. 12 ( 2021-12), p. 1365-1376
    Type of Medium: Online Resource
    ISSN: 2213-2600
    URL: Article
    DOI: 10.1016/S2213-2600(21)00384-2
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017–2020
    Oxford University Press (OUP) ; 2022
    In:  Clinical Infectious Diseases Vol. 74, No. 6 ( 2022-03-23), p. 1004-1011
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 74, No. 6 ( 2022-03-23), p. 1004-1011
    Abstract: Respiratory syncytial virus (RSV) causes acute respiratory illness (ARI) and triggers exacerbations of cardiopulmonary disease. Estimates of incidence in hospitalized adults range widely, with few data on incidence in adults with comorbidities that increase the risk of severity. We conducted a prospective, population-based, surveillance study to estimate incidence of RSV hospitalization among adults overall and those with specific comorbidities. Methods Hospitalized adults aged ≥18 years residing in the surveillance area with ≥2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened during the 2017–2018, 2018–2019, and 2019–2020 RSV seasons in 3 hospitals in Rochester, New York and New York City. Respiratory specimens were tested for RSV using polymerase chain reaction assays. RSV incidence per 100 000 was adjusted by market share. Results Active and passive surveillance identified 1099 adults hospitalized with RSV. Annual incidence during 3 seasons ranged from 44.2 to 58.9/100 000. Age-group–specific incidence ranged from 7.7 to 11.9/100 000, 33.5 to 57.5/100 000, and 136.9 to 255.6/100 000 in patients ages 18–49, 50–64, and ≥65 years, respectively. Incidence rates in patients with chronic obstructive pulmonary disease, coronary artery disease, and congestive heart failure were 3–13, 4–7, and 4–33 times, respectively, the incidence in patients without these conditions. Conclusions We found a high burden of RSV hospitalization in this large prospective study. Notable was the high incidence among older patients and those with cardiac conditions. These data confirm the need for effective vaccines to prevent RSV infection in older and vulnerable adults.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciab595
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2002229-3
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  • 4
    Online Resource
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    Gene Expression Risk Scores for COVID-19 Illness Severity
    Oxford University Press (OUP) ; 2023
    In:  The Journal of Infectious Diseases Vol. 227, No. 3 ( 2023-02-01), p. 322-331
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 227, No. 3 ( 2023-02-01), p. 322-331
    Abstract: The correlates of coronavirus disease 2019 (COVID-19) illness severity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are incompletely understood. Methods We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2 infection clinically adjudicated as having mild, moderate, or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and nonsevere COVID-19. Results Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus nonsevere illness, we identified & gt;4000 genes differentially expressed (false discovery rate & lt; 0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T-cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated receiver operating characteristic-area under the curve [ROC-AUC] = 0.98), and need for intensive care in an independent cohort (ROC-AUC = 0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort. Conclusions These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiab568
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 5
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    Real-life Assessment of BioFire FilmArray Pneumonia Panel in Adults Hospitalized With Respiratory Illness
    Oxford University Press (OUP) ; 2023
    In:  The Journal of Infectious Diseases ( 2023-06-27)
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), ( 2023-06-27)
    Abstract: Inability to identify the microbial etiology of lower respiratory tract infection leads to unnecessary antibiotic use. We evaluated the utility of the BioFire FilmArray Pneumonia Panel (BioFire PN) to inform microbiologic diagnosis. Methods Hospitalized adults with respiratory illness were recruited; sputa and clinical/laboratory data were collected. Sputa were cultured for bacteria and tested with BioFire PN. Microbial etiology was adjudicated by 4 physicians. Bacterial polymerase chain reaction (PCR) was compared with culture and clinical adjudication. Results Of 298 sputa tested, BioFire PN detected significantly more pathogens (350 bacteria, 16 atypicals, and 164 viruses) than sputum culture plus any standard-of-care testing (91% vs 60%, P & lt; .0001). When compared with culture, the sensitivity of BioFire PN for individual bacteria was 46% to 100%; specificity, 61% to 100%; and negative predictive value, 92% to 100%. Cases were adjudicated as viral (n = 58) and bacterial (n = 100). PCR detected bacteria in 55% of viral cases and 95% of bacterial (P & lt; .0001). High serum procalcitonin and bacterial adjudication were more often associated with sputa with 106 or 107 copies detected. Conclusions Multiplex PCR testing of sputa for bacteria is useful to rule out bacterial infection with added value to detect viruses and atypical bacteria.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiad221
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 6
    Online Resource
    Online Resource
    Identifying Gaps in Respiratory Syncytial Virus Disease Epidemiology in the United States Prior to the Introduction of Vaccines
    Oxford University Press (OUP) ; 2017
    In:  Clinical Infectious Diseases Vol. 65, No. 6 ( 2017-09-15), p. 1020-1025
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 65, No. 6 ( 2017-09-15), p. 1020-1025
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/cix432
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 2002229-3
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  • 7
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    2755. Phase 1/2, First-in-Human Study of the Safety, Tolerability, and Immunogenicity of an RSV Prefusion F-Based Subunit Vaccine Candidate
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S970-S970
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S970-S970
    Abstract: The respiratory syncytial virus (RSV) fusion glycoprotein (F) is a molecule that fuses the viral and host cell membranes during virus entry as it rearranges from a meta-stable prefusion to a stable postfusion conformation. Using structure-guided design, Pfizer engineered a prefusion RSV F subunit vaccine antigen with stable and well-characterized conformational homogeneity. Methods We report results of a 1,182 subject, first-in-human, phase 1/2, placebo-controlled, randomized, observer-blind, dose-finding study to describe the safety, tolerability, and immunogenicity of the Pfizer RSV vaccine candidate in healthy men and non-pregnant women from 18 to 85 years of age. The study compares three dosages of the vaccine candidate, with and without aluminum hydroxide, and also compares immunization with the RSV vaccine candidate alone or concomitantly with influenza vaccine. The study is ongoing to collect antibody persistence and additional safety data. Results The data, which are currently available for the 18- to 49-year-old subgroup, demonstrate an excellent safety and tolerability profile. Immunization with the various formulations of the vaccine candidate elicited RSV 50% neutralization titer geometric mean fold rises (GMFRs) of 10.6–17.2 for subgroup A and 10.4–19.8 for subgroup B, measured one month after immunization, with evidence of a dose–response. Conclusion The 10- to 20-fold increases in neutralizing antibody titers elicited by this vaccine with a stable prefusion F antigen represent a step change relative to the historical performance of vaccine candidates, such as Wyeth’s PFP, with F antigens that were not stabilized in the prefusion conformation (Simoes et al., Vaccine 20:954–60, 2002). The data strongly support development of this vaccine candidate to prevent RSV disease in infants, by immunizing pregnant women, and to prevent RSV disease in older adults, by direct immunization. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz360.2432
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 8
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    2315. The Relationship of Pre-Hospital Functional Status and Clinical Outcomes in Patients with Laboratory-Confirmed RSV Infection: Active Population-Based Surveillance, 2017–2019
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S794-S794
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S794-S794
    Abstract: Respiratory syncytial virus (RSV) infection is a common cause of acute respiratory infection (ARI) in adults. Prospective surveillance enables collection of representative data on demographic and clinical characteristics. Few data of this kind are available for adults hospitalized with RSV infection. We used active population-based surveillance to identify patients with laboratory-confirmed RSV infection and evaluated demographic characteristics and clinical outcomes. Methods Hospitalized adults ≥ 18 years old residing in a predefined catchment area with ≥ 2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018–April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. Clinical and demographic data were abstracted from the medical record. Multivariate analysis was used to evaluate the relationship of patient characteristics with clinical outcomes. Results 8,217 hospitalized adults were screened and 9.4% positive for RSV infection. Preliminary clinical and demographic data were available for 348 patients including 14% 18–49 years, 28% 50–64 years and 58% 〉 65 years. Mean age was 68 years and 60% were female (Figure 1). Patients had a mean of 3 co-morbidities, with diabetes (40%), chronic obstructive pulmonary disease (30%), chronic kidney disease (28%), congestive heart failure (28%), coronary artery disease (25%) and asthma (24%) the most common co-morbidities (Figure 2). Median hospital length of stay was 6 days (IQR 4–10), 13% of patients were admitted to the ICU, 5% were mechanically ventilated and 5% died during admission and 12% within 6 months. In multivariate analysis having 〉 3 comorbidities, cardiac disease or a lower baseline functional status measured by activities of daily living scores was significantly associated with 6-month mortality. Conclusion The majority of hospitalized patients with RSV infection were older adults with ≥ 3 chronic comorbid conditions. Baseline functional status may be predictive of worse clinical outcomes in patients with RSV infection. These insights into patient characteristics and clinical outcomes will provide information for prevention programs. Disclosures All authors: No reported disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz360.1993
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2757767-3
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  • 9
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    92. Incidence of Respiratory Syncytial Virus Infection among Hospitalized Adults, 2017–2019
    Oxford University Press (OUP) ; 2019
    In:  Open Forum Infectious Diseases Vol. 6, No. Supplement_2 ( 2019-10-23), p. S7-S8
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 6, No. Supplement_2 ( 2019-10-23), p. S7-S8
    Abstract: Respiratory syncytial virus (RSV) infection has been increasingly recognized as an important cause of acute respiratory illness (ARI) and a trigger for exacerbation of underlying cardiopulmonary disease in adults. Incidence of hospitalized RSV infection remains uncertain as adults have not been systematically screened. Previous incidence estimates, derived primarily from modeling studies, have ranged from 84 to 190/100K population in adults 〉 65 years of age. Accurate burden data are critical to inform RSV vaccine development for adults. We used active surveillance among hospitalized adults to determine population-based incidence rates of RSV infection. Methods Hospitalized adults ≥ 18 years old residing in the surveillance area with 〉 2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018 to April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. RSV incidence per 100,000 persons (per 2010 US Census data) was adjusted by percent market share for study hospitals in their catchment area. Results In total, 8,217 hospitalized adults residing in the surveillance area that met the surveillance case definition were tested for RSV; 768 (9.4%) were positive. Adults were aged 18–49 (12%), 50–64 (30%), and ≥65 years old (58%); 55% were female. RSV infection incidence varied from year 1 to year 2 and was highest in patients aged ≥65 years old (table). Conclusion This is the largest prospective RSV incidence study to date. Preliminary results indicate that the incidence of RSV infection may be higher than previously reported, especially in urban-dwelling adults 〉 65 years of age. Results confirm the need for vaccines to prevent RSV infections in older adults. Disclosures All Authors: No reported Disclosures.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofz359.016
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 10
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    Perturbations in Respiratory Syncytial Virus Activity During the SARS-CoV-2 Pandemic
    Oxford University Press (OUP) ; 2022
    In:  The Journal of Infectious Diseases Vol. 227, No. 1 ( 2022-12-28), p. 83-86
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 227, No. 1 ( 2022-12-28), p. 83-86
    Abstract: Respiratory syncytial virus (RSV) is a common cause of respiratory disease in all age groups, with young children and older adults experiencing the most severe illness. The coronavirus disease 2019 (COVID-19) pandemic resulted in striking changes in the activity of seasonal respiratory viruses, including RSV. After a period of suppression early in the pandemic, an interseasonal surge of RSV occurred in 2021. Viral activity was detected primarily in children and young adults after relaxation of public health measures, but without the usual proportional increases in infections and hospitalizations in older adults who were likely still adhering to stricter public health measures.
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Article
    DOI: 10.1093/infdis/jiac434
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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