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Article ; Online: The antibiotic resistance reservoir of the lung microbiome expands with age in a population of critically ill patients.

Chu, Victoria T / Tsitsiklis, Alexandra / Mick, Eran / Ambroggio, Lilliam / Kalantar, Katrina L / Glascock, Abigail / Osborne, Christina M / Wagner, Brandie D / Matthay, Michael A / DeRisi, Joseph L / Calfee, Carolyn S / Mourani, Peter M / Langelier, Charles R

Nature communications

2024 Volume 15, Issue 1, Page(s) 92

Abstract: Antimicrobial resistant lower respiratory tract infections are an increasing public health threat and an important cause of global mortality. The lung microbiome can influence susceptibility of respiratory tract infections and represents an important ... ...

Abstract	Antimicrobial resistant lower respiratory tract infections are an increasing public health threat and an important cause of global mortality. The lung microbiome can influence susceptibility of respiratory tract infections and represents an important reservoir for exchange of antimicrobial resistance genes. Studies of the gut microbiome have found an association between age and increasing antimicrobial resistance gene burden, however, corollary studies in the lung microbiome remain absent. We performed an observational study of children and adults with acute respiratory failure admitted to the intensive care unit. From tracheal aspirate RNA sequencing data, we evaluated age-related differences in detectable antimicrobial resistance gene expression in the lung microbiome. Using a multivariable logistic regression model, we find that detection of antimicrobial resistance gene expression was significantly higher in adults compared with children after adjusting for demographic and clinical characteristics. This association remained significant after additionally adjusting for lung bacterial microbiome characteristics, and when modeling age as a continuous variable. The proportion of adults expressing beta-lactam, aminoglycoside, and tetracycline antimicrobial resistance genes was higher compared to children. Together, these findings shape our understanding of the lung resistome in critically ill patients across the lifespan, which may have implications for clinical management and global public health.
MeSH term(s)	Adult ; Child ; Humans ; Critical Illness ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Microbiota/genetics ; Lung ; Drug Resistance, Microbial/genetics ; Respiratory Tract Infections/drug therapy
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Observational Study ; Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44353-1
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Article: Examination of Common Coronavirus Antibodies in SARS-CoV-2-Infected and Uninfected Participants in a Household Transmission Investigation.

Stumpf, Megan M / Freeman, Brandi / Mills, Lisa / Lester, Sandra / Chu, Victoria T / Kirking, Hannah L / Thornburg, Natalie J / Killerby, Marie E

Open forum infectious diseases

2022 Volume 9, Issue 7, Page(s) ofac212

Abstract: We compared paired serum specimens from household contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases with detectable SARS-CoV-2 seroconversion with contacts who remained seronegative. No protection from SARS-CoV-2 infection ... ...

Abstract	We compared paired serum specimens from household contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases with detectable SARS-CoV-2 seroconversion with contacts who remained seronegative. No protection from SARS-CoV-2 infection was associated with human coronavirus antibodies; however, an increase in common betacoronavirus antibodies was associated with seroconversion to SARS-CoV-2 in mild to moderately ill cases.
Language	English
Publishing date	2022-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofac212
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Article: The antibiotic resistance reservoir of the lung microbiome expands with age.

Research square

2023

Abstract: Antimicrobial resistant lower respiratory tract infections (LRTI) are an increasing public health threat, and an important cause of global mortality. The lung microbiome influences LRTI susceptibility and represents an important reservoir for exchange of ...

Abstract	Antimicrobial resistant lower respiratory tract infections (LRTI) are an increasing public health threat, and an important cause of global mortality. The lung microbiome influences LRTI susceptibility and represents an important reservoir for exchange of antimicrobial resistance genes (ARGs). Studies of the gut microbiome have found an association between age and increasing antimicrobial resistance gene (ARG) burden, however corollary studies in the lung microbiome remain absent, despite the respiratory tract representing one of the most clinically significant sites for drug resistant infections. We performed a prospective, multicenter observational study of 261 children and 88 adults with acute respiratory failure, ranging in age from 31 days to ≥ 89 years, admitted to intensive care units in the United States. We performed RNA sequencing on tracheal aspirates collected within 72 hours of intubation, and evaluated age-related differences in detectable ARG expression in the lung microbiome as a primary outcome. Secondary outcomes included number and classes of ARGs detected, proportion of patients with an ARG class, and composition of the lung microbiome. Multivariable logistic regression models (adults vs children) or continuous age (years) were adjusted for sex, race/ethnicity, LRTI status, and days from intubation to specimen collection. Detection of ARGs was significantly higher in adults compared with children after adjusting for sex, race/ethnicity, LRTI diagnosis, and days from intubation to specimen collection (adjusted odds ratio (aOR): 2.16, 95% confidence interval (CI): 1.10-4.22). A greater proportion of adults compared with children had beta-lactam ARGs (31% (CI: 21-41%) vs 13% (CI: 10-18%)), aminoglycoside ARGs (20% (CI: 13-30%) vs 2% (CI: 0.6-4%)), and tetracycline ARGs (14% (CI: 7-23%) vs 3% (CI: 1-5%)). Adults ≥70 years old had the highest proportion of these three ARG classes. The total bacterial abundance of the lung microbiome increased with age, and microbiome alpha diversity varied with age. Taxonomic composition of the lung microbiome, measured by Bray Curtis dissimilarity index, differed between adults and children (p = 0.003). The association between age and increased ARG detection remained significant after additionally including lung microbiome total bacterial abundance and alpha diversity in the multivariable logistic regression model (aOR: 2.38, (CI: 1.25-4.54)). Furthermore, this association remained robust when modeling age as a continuous variable (aOR: 1.02, (CI: 1.01-1.03) per year of age). Taken together, our results demonstrate that age is an independent risk factor for ARG detection in the lower respiratory tract microbiome. These data shape our understanding of the lung resistome in critically ill patients across the lifespan, which may have implications for clinical management and global public health.
Language	English
Publishing date	2023-09-18
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3283415/v1
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Article: Simultaneous detection of pathogens and antimicrobial resistance genes with the open source, cloud-based, CZ ID pipeline.

Lu, Dan / Kalantar, Katrina L / Chu, Victoria T / Glascock, Abigail L / Guerrero, Estella S / Bernick, Nina / Butcher, Xochitl / Ewing, Kirsty / Fahsbender, Elizabeth / Holmes, Olivia / Hoops, Erin / Jones, Ann E / Lim, Ryan / McCanny, Suzette / Reynoso, Lucia / Rosario, Karyna / Tang, Jennifer / Valenzuela, Omar / Mourani, Peter M /

Pickering, Amy J / Raphenya, Amogelang R / Alcock, Brian P / McArthur, Andrew G / Langelier, Charles R

bioRxiv : the preprint server for biology

2024

Abstract: Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of ...

Abstract	Antimicrobial resistant (AMR) pathogens represent urgent threats to human health, and their surveillance is of paramount importance. Metagenomic next generation sequencing (mNGS) has revolutionized such efforts, but remains challenging due to the lack of open-access bioinformatics tools capable of simultaneously analyzing both microbial and AMR gene sequences. To address this need, we developed the Chan Zuckerberg ID (CZ ID) AMR module, an open-access, cloud-based workflow designed to integrate detection of both microbes and AMR genes in mNGS and whole-genome sequencing (WGS) data. It leverages the Comprehensive Antibiotic Resistance Database and associated Resistance Gene Identifier software, and works synergistically with the CZ ID short-read mNGS module to enable broad detection of both microbes and AMR genes. We highlight diverse applications of the AMR module through analysis of both publicly available and newly generated mNGS and WGS data from four clinical cohort studies and an environmental surveillance project. Through genomic investigations of bacterial sepsis and pneumonia cases, hospital outbreaks, and wastewater surveillance data, we gain a deeper understanding of infectious agents and their resistomes, highlighting the value of integrating microbial identification and AMR profiling for both research and public health. We leverage additional functionalities of the CZ ID mNGS platform to couple resistome profiling with the assessment of phylogenetic relationships between nosocomial pathogens, and further demonstrate the potential to capture the longitudinal dynamics of pathogen and AMR genes in hospital acquired bacterial infections. In sum, the new AMR module advances the capabilities of the open-access CZ ID microbial bioinformatics platform by integrating pathogen detection and AMR profiling from mNGS and WGS data. Its development represents a critical step toward democratizing pathogen genomic analysis and supporting collaborative efforts to combat the growing threat of AMR.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.12.589250
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Article ; Online: Whole-genome sequencing rule-out of suspected hospital-onset

Chu, Victoria T / Nafees, Saba / Waltari, Eric / McNeil, Nicole / Caughell, Carolyn / Sanchez-Guerrero, Estella / Wang, Lusha / Stanley, Kim / Cunningham, Gail / Wong, Joan / Phelps, Maíra / Tato, Cristina M / Miller, Steve / DeRisi, Joseph L / Yokoe, Deborah S / Ramirez-Avila, Lynn / Langelier, Charles R

Infection control and hospital epidemiology

2023 Volume 44, Issue 12, Page(s) 2059–2061

Abstract: Two independent temporal-spatial clusters of hospital- ... ...

Abstract	Two independent temporal-spatial clusters of hospital-onset
MeSH term(s)	Humans ; Rhizopus/genetics ; Phylogeny ; Genome, Bacterial ; Hospitals ; Disease Outbreaks
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	639378-0
ISSN	1559-6834 ; 0195-9417 ; 0899-823X
ISSN (online)	1559-6834
ISSN	0195-9417 ; 0899-823X
DOI	10.1017/ice.2023.85
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Article ; Online: Factors Associated with Participation in Elementary School-Based SARS-CoV-2 Testing - Salt Lake County, Utah, December 2020-January 2021.

Lewis, Nathaniel M / Hershow, Rebecca B / Chu, Victoria T / Wu, Karen / Milne, Alison T / LaCross, Nathan / Hill, Mary / Risk, Ilene / Hersh, Adam L / Kirking, Hannah L / Tate, Jacqueline E / Vallabhaneni, Snigdha / Dunn, Angela C

MMWR. Morbidity and mortality weekly report

2021 Volume 70, Issue 15, Page(s) 557–559

Abstract: During December 3, 2020-January 31, 2021, CDC, in collaboration with the University of Utah Health and Economic Recovery Outreach Project,* Utah Department of Health (UDOH), Salt Lake County Health Department, and one Salt Lake county school district, ... ...

Abstract	During December 3, 2020-January 31, 2021, CDC, in collaboration with the University of Utah Health and Economic Recovery Outreach Project,* Utah Department of Health (UDOH), Salt Lake County Health Department, and one Salt Lake county school district, offered free, in-school, real-time reverse transcription-polymerase chain reaction (RT-PCR) saliva testing as part of a transmission investigation of SARS-CoV-2, the virus that causes COVID-19, in elementary school settings. School contacts
MeSH term(s)	COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19/transmission ; COVID-19 Nucleic Acid Testing/statistics & numerical data ; Child ; Contact Tracing ; Humans ; School Health Services/statistics & numerical data ; Schools/statistics & numerical data ; Socioeconomic Factors ; Utah/epidemiology
Language	English
Publishing date	2021-04-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	412775-4
ISSN	1545-861X ; 0149-2195
ISSN (online)	1545-861X
ISSN	0149-2195
DOI	10.15585/mmwr.mm7015e1
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Article ; Online: Performance of existing and novel surveillance case definitions for COVID-19 in household contacts of PCR-confirmed COVID-19.

Reses, Hannah E / Fajans, Mark / Lee, Scott H / Heilig, Charles M / Chu, Victoria T / Thornburg, Natalie J / Christensen, Kim / Bhattacharyya, Sanjib / Fry, Alicia / Hall, Aron J / Tate, Jacqueline E / Kirking, Hannah L / Nabity, Scott A

BMC public health

2021 Volume 21, Issue 1, Page(s) 1747

Abstract: Background: Optimized symptom-based COVID-19 case definitions that guide public health surveillance and individual patient management in the community may assist pandemic control.: Methods: We assessed diagnostic performance of existing cases ... ...

Abstract	Background: Optimized symptom-based COVID-19 case definitions that guide public health surveillance and individual patient management in the community may assist pandemic control. Methods: We assessed diagnostic performance of existing cases definitions (e.g. influenza-like illness, COVID-like illness) using symptoms reported from 185 household contacts to a PCR-confirmed case of COVID-19 in Wisconsin and Utah, United States. We stratified analyses between adults and children. We also constructed novel case definitions for comparison. Results: Existing COVID-19 case definitions generally showed high sensitivity (86-96%) but low positive predictive value (PPV) (36-49%; F-1 score 52-63) in this community cohort. Top performing novel symptom combinations included taste or smell dysfunction and improved the balance of sensitivity and PPV (F-1 score 78-80). Performance indicators were generally lower for children (< 18 years of age). Conclusions: Existing COVID-19 case definitions appropriately screened in household contacts with COVID-19. Novel symptom combinations incorporating taste or smell dysfunction as a primary component improved accuracy. Case definitions tailored for children versus adults should be further explored.
MeSH term(s)	Adult ; COVID-19 ; Child ; Cohort Studies ; Humans ; Pandemics ; Polymerase Chain Reaction ; SARS-CoV-2
Language	English
Publishing date	2021-09-25
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2041338-5
ISSN	1471-2458 ; 1471-2458
ISSN (online)	1471-2458
ISSN	1471-2458
DOI	10.1186/s12889-021-11683-y
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Article ; Online: Comparison of the SARS-CoV-2 spike protein ELISA and the Abbott Architect SARS-CoV-2 IgG nucleocapsid protein assays for detection of antibodies.

Wadhwa, Ashutosh / Yin, Sherry / Freeman, Brandi / Hershow, Rebecca B / Killerby, Marie / Yousaf, Anna R / Lester, Sandra / Mills, Lisa / Buono, Sean A / Pomeroy, Mary / Owusu, Daniel / Chu, Victoria T / Tate, Jacqueline E / Bhattacharyya, Sanjib / Hall, Patricia / Thornburg, Natalie J / Kirking, Hannah L

PloS one

2021 Volume 16, Issue 7, Page(s) e0255208

Abstract: Serologic assays developed for SARS-CoV-2 detect different antibody subtypes and are based on different target antigens. Comparison of the performance of a SARS-CoV-2 Spike-Protein ELISA and the nucleocapsid-based Abbott ArchitectTM SARS-CoV-2 IgG assay ... ...

Abstract	Serologic assays developed for SARS-CoV-2 detect different antibody subtypes and are based on different target antigens. Comparison of the performance of a SARS-CoV-2 Spike-Protein ELISA and the nucleocapsid-based Abbott ArchitectTM SARS-CoV-2 IgG assay indicated that the assays had high concordance, with rare paired discordant tests results.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Viral/immunology ; COVID-19/diagnosis ; COVID-19/virology ; Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Humans ; Immunoglobulin G/immunology ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Nucleocapsid/immunology ; Nucleocapsid Proteins/immunology ; SARS-CoV-2/immunology ; Sensitivity and Specificity ; Spike Glycoprotein, Coronavirus/immunology ; Young Adult
Chemical Substances	Antibodies, Viral ; Immunoglobulin G ; Nucleocapsid Proteins ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-07-29
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0255208
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Article ; Online: Behaviors Associated With Household Transmission of SARS-CoV-2 in California and Colorado, January 2021-April 2021.

Namageyo-Funa, Apophia / Ruffin, Jasmine D / Killerby, Marie E / Jalloh, Mohamed F / Scott, Colleen / Lindell, Kristine / Silver, Margaret / Matanock, Almea / Soto, Raymond A / Donnelly, Marisa A P / Schwartz, Noah G / Chuey, Meagan R / Chu, Victoria T / Beatty, Mark E / Totten, Sarah Elizabeth / Hudziec, Meghan M / Tate, Jacqueline E / Kirking, Hannah L / Hsu, Christopher H

AJPM focus

2022 Volume 1, Issue 1, Page(s) 100004

Abstract: Introduction: Mitigation behaviors are key to preventing SARS-CoV-2 transmission. We identified the behaviors associated with secondary transmission from confirmed SARS-CoV-2 primary cases to household contacts and described the characteristics ... ...

Abstract	Introduction: Mitigation behaviors are key to preventing SARS-CoV-2 transmission. We identified the behaviors associated with secondary transmission from confirmed SARS-CoV-2 primary cases to household contacts and described the characteristics associated with reporting these behaviors. Methods: Households with confirmed SARS-CoV-2 infections were recruited in California and Colorado from January to April 2021. Self-reported behaviors and demographics were collected through interviews. We investigated behaviors associated with transmission and individual and household characteristics associated with behaviors using univariable and multivariable logistic regression with generalized estimating equations to account for household clustering. Results: Among household contacts of primary cases, 43.3% (133 of 307) became infected with SARS-CoV-2. When an adjusted analysis was conducted, household contacts who slept in the same bedroom with the primary case (AOR=2.19; 95% CI=1.25, 3.84) and ate food prepared by the primary case (AOR=1.98; 95% CI=1.02, 3.87) had increased odds of SARS-CoV-2 infection. Household contacts in homes ≤2,000 square feet had increased odds of sleeping in the same bedroom as the primary case compared with those in homes >2,000 square feet (AOR=3.97; 95% CI=1.73, 9.10). Parents, siblings, and other relationships (extended family, friends, or roommates) of the primary case had decreased odds of eating food prepared by the primary case compared with partners. Conclusions: Sleeping in the same bedroom as the primary case and eating food prepared by the primary case were associated with secondary transmission. Household dimension and relationship to the primary case were associated with these behaviors. Our findings encourage innovative means to promote adherence to mitigation measures that reduce household transmission.
Language	English
Publishing date	2022-05-05
Publishing country	England
Document type	Journal Article
ISSN	2773-0654
ISSN (online)	2773-0654
DOI	10.1016/j.focus.2022.100004
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Article ; Online: Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020.

Bajema, Kristina L / Oster, Alexandra M / McGovern, Olivia L / Lindstrom, Stephen / Stenger, Mark R / Anderson, Tara C / Isenhour, Cheryl / Clarke, Kevin R / Evans, Mary E / Chu, Victoria T / Biggs, Holly M / Kirking, Hannah L / Gerber, Susan I / Hall, Aron J / Fry, Alicia M / Oliver, Sara E

MMWR. Morbidity and mortality weekly report

2020 Volume 69, Issue 6, Page(s) 166–170

Abstract: In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February ...

Abstract	In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.
MeSH term(s)	Adolescent ; Adult ; Aged ; Betacoronavirus/isolation & purification ; COVID-19 ; Centers for Disease Control and Prevention, U.S. ; Child ; Child, Preschool ; Contact Tracing ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Disease Outbreaks/prevention & control ; Female ; Humans ; Male ; Mass Screening/statistics & numerical data ; Middle Aged ; Pandemics ; Pneumonia, Viral/virology ; Risk Assessment ; SARS-CoV-2 ; Travel-Related Illness ; United States/epidemiology ; Young Adult
Keywords	covid19
Language	English
Publishing date	2020-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	412775-4
ISSN	1545-861X ; 0149-2195
ISSN (online)	1545-861X
ISSN	0149-2195
DOI	10.15585/mmwr.mm6906e1
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