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Article ; Online: Impact of Respiratory Viral Infections in Transplant Recipients.

Bahakel, Hannah / Waghmare, Alpana / Madan, Rebecca Pellet

Journal of the Pediatric Infectious Diseases Society

2024 Volume 13, Issue Supplement_1, Page(s) S39–S48

Abstract: Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed ... ...

Abstract	Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed bacterial and fungal pneumonia, chronic graft dysfunction, and graft failure as a result of RVIs. Recent multicenter retrospective studies and prospective studies utilizing contemporary molecular diagnostic techniques have better delineated the epidemiology and outcomes of RVIs in pediatric transplant recipients and have advanced the development of preventative vaccines and treatment interventions in this population. In this review, we will define the epidemiology and outcomes of RVIs in SOT and HSCT recipients, describe the available assays for diagnosing a suspected RVI, highlight evolving management and vaccination strategies, review the risk of donor derived RVI in SOT recipients, and discuss considerations for delaying transplantation in the presence of an RVI.
MeSH term(s)	Humans ; Child ; Respiratory Tract Infections/diagnosis ; Transplant Recipients ; Retrospective Studies ; Prospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects ; Influenza, Human
Language	English
Publishing date	2024-03-01
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2668791-4
ISSN	2048-7207 ; 2048-7193
ISSN (online)	2048-7207
ISSN	2048-7193
DOI	10.1093/jpids/piad094
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Article: Approach to hematopoietic cell transplant candidates with respiratory viral detection.

Kim, Sara R / Waghmare, Alpana / Hijano, Diego R

Frontiers in pediatrics

2024 Volume 11, Page(s) 1339239

Abstract: The management of respiratory viruses prior to hematopoietic cell transplant (HCT) can be controversial and requires special consideration of host factors, transplant parameters, and the specific respiratory virus (RV). In the setting of adenovirus (ADV), ...

Abstract	The management of respiratory viruses prior to hematopoietic cell transplant (HCT) can be controversial and requires special consideration of host factors, transplant parameters, and the specific respiratory virus (RV). In the setting of adenovirus (ADV), human metapneumovirus (HMPV), influenza, parainfluenza virus (PIV), and respiratory syncytial virus (RSV) detection prior to hematopoietic cell transplant (HCT), clinical practice guidelines recommend transplant delay when possible; however, there is much more ambiguity when other respiratory viruses, such as seasonal coronaviruses (CoVs), human rhinovirus (HRV), and SARS-CoV-2, are detected. Our aims for this review include detailing clinical practical guidelines and reviewing current literature on pre-transplant respiratory viral infections (RVIs), including antiviral therapies and prevention strategies, when available. We will center our discussion on three representative clinical scenarios, with the goal of providing practical guidance to clinicians.
Language	English
Publishing date	2024-01-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2023.1339239
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Article ; Online: Unraveling the lung metatranscriptome in HCT.

Waghmare, Alpana / Gharib, Sina A

Blood

2021 Volume 137, Issue 12, Page(s) 1570–1572

MeSH term(s)	Humans ; Lung/diagnostic imaging
Language	English
Publishing date	2021-04-05
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020010539
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Article ; Online: SARS-CoV-2 Infection and COVID-19 in Children.

Waghmare, Alpana / Hijano, Diego R

Clinics in chest medicine

2022 Volume 44, Issue 2, Page(s) 359–371

Abstract: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but ... ...

Abstract	Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is common in children, and clinical manifestations can vary depending on age, underlying disease, and vaccination status. Most children will have asymptomatic or mild infection, but certain baseline characteristics can increase the risk of moderate to severe disease. The following article will provide an overview of the clinical manifestations of coronavirus disease 2019 in children, including the post-infectious phenomenon called multisystem inflammatory syndrome in children. Currently available treatment and prophylaxis strategies will be outlined, with the caveat that new therapeutics and clinical efficacy data are constantly on the horizon.
MeSH term(s)	Child ; Humans ; COVID-19 ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/therapy
Language	English
Publishing date	2022-11-22
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	447455-7
ISSN	1557-8216 ; 0272-5231
ISSN (online)	1557-8216
ISSN	0272-5231
DOI	10.1016/j.ccm.2022.11.014
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Article ; Online: Monoclonal antibodies for prophylaxis and treatment of respiratory viral infections.

Boonyaratanakornkit, Jim / Boeckh, Michael / Waghmare, Alpana

Current opinion in infectious diseases

2022 Volume 35, Issue 4, Page(s) 280–287

Abstract: Purpose of review: Monoclonal antibody (mAb) administration represents an important strategy for preventing and treating respiratory viral infections in vulnerable populations, including immunocompromised individuals. The purpose of this review is to ... ...

Abstract	Purpose of review: Monoclonal antibody (mAb) administration represents an important strategy for preventing and treating respiratory viral infections in vulnerable populations, including immunocompromised individuals. The purpose of this review is to provide an overview of mAbs in clinical use against respiratory viruses, highlight factors that modulate mAb clinical efficacy, and provide a perspective on future innovations in the field. This review focuses on publications from the last year. Recent findings: Historically, clinical development of a single mAb has taken over a decade. The COVID-19 pandemic has demonstrated that this timeframe can be reduced to less than a year and has catalyzed rapid innovations in the field. Several novel mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have received emergency use authorization by the Food and Drug Administration (FDA) for the early treatment of mild to moderate COVID-19. However, the majority of these mAbs have ultimately failed due to the emergence of variants, highlighting an important lesson about predicting and countering resistance. Novel mAbs are also in clinical use or in late-stage development for the prevention of infection by SARS-CoV-2 and respiratory syncytial virus (RSV) in vulnerable populations. Several factors can be modulated to improve the clinical efficacy of mAbs. For example, Fc modifications can extend mAb half-life and increase respiratory tract bioavailability, both of which are attractive properties for achieving protection against respiratory viruses. Summary: The mAb landscape is rapidly evolving with numerous examples of success and failure. The armamentarium of clinically-available mAbs to protect vulnerable populations is expected to undergo continued growth.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Antibodies, Viral ; COVID-19/prevention & control ; Humans ; Pandemics ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus Infections/prevention & control ; SARS-CoV-2 ; Viruses
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	645085-4
ISSN	1473-6527 ; 1535-3877 ; 0951-7375 ; 1355-834X
ISSN (online)	1473-6527 ; 1535-3877
ISSN	0951-7375 ; 1355-834X
DOI	10.1097/QCO.0000000000000846
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Article ; Online: Within-Host Rhinovirus Evolution in Upper and Lower Respiratory Tract Highlights Capsid Variability and Mutation-Independent Compartmentalization.

Makhsous, Negar / Goya, Stephanie / Avendaño, Carlos C / Rupp, Jason / Kuypers, Jane / Jerome, Keith R / Boeckh, Michael / Waghmare, Alpana / Greninger, Alexander L

The Journal of infectious diseases

2024 Volume 229, Issue 2, Page(s) 403–412

Abstract: Background: Rhinovirus (RV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how RV evolves within hosts during infection.: ... ...

Abstract	Background: Rhinovirus (RV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how RV evolves within hosts during infection. Methods: We sequenced RV complete genomes from 12 hematopoietic cell transplant patients with infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL). Metagenomic and amplicon next-generation sequencing were used to track the emergence and evolution of intrahost single nucleotide variants (iSNVs). Results: Identical RV intrahost populations in matched NW and BAL specimens indicated no genetic adaptation is required for RV to progress from URT to LRT. Coding iSNVs were 2.3-fold more prevalent in capsid over nonstructural genes. iSNVs modeled were significantly more likely to be found in capsid surface residues, but were not preferentially located in known RV-neutralizing antibody epitopes. Newly emergent, genotype-matched iSNV haplotypes from immunocompromised individuals in 2008-2010 could be detected in Seattle-area community RV sequences in 2020-2021. Conclusions: RV infections in immunocompromised hosts can progress from URT to LRT with no specific evolutionary requirement. Capsid proteins carry the highest variability and emergent mutations can be detected in other, including future, RV sequences.
MeSH term(s)	Humans ; Capsid Proteins/genetics ; Capsid ; Rhinovirus/genetics ; Hematopoietic Stem Cell Transplantation ; Mutation ; Enterovirus Infections
Chemical Substances	Capsid Proteins
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad284
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Article ; Online: 21 Respiratory viruses

Waghmare, Alpana / Englund, Janet A.

Pediatric Transplant and Oncology Infectious Diseases

Abstract: Abstract: Respiratory viruses are commonly detected in both healthy and immunocompromised children. In most healthy children, respiratory viruses are associated with self-limited upper respiratory tract infections and are not accompanied by significant ... ...

Abstract	Abstract: Respiratory viruses are commonly detected in both healthy and immunocompromised children. In most healthy children, respiratory viruses are associated with self-limited upper respiratory tract infections and are not accompanied by significant morbidity. In immunocompromised hosts, including hematopoietic cell transplant recipients, solid organ transplant recipients, and oncology patients, respiratory viruses can be associated with significant clinical manifestations, including prolonged viral shedding, lower respiratory tract disease, the need for supplemental oxygen, late airflow obstruction, and even death. This chapter reviews the major respiratory viruses, including respiratory syncytial virus, human metapneumovirus, influenza, parainfluenza viruses, human rhinoviruses, and human coronaviruses. Other viruses can manifest as pulmonary infection; however, these viruses are discussed elsewhere (see Chapter 17 for discussion of cytomegalovirus and Chapter 22 for discussion of adenoviruses).
Keywords	covid19
Publisher	Elsevier; PMC
Document type	Article ; Online
DOI	10.1016/b978-0-323-64198-2.00030-0
Database	COVID19

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Article: Within-host rhinovirus evolution in upper and lower respiratory tract highlights capsid variability and mutation-independent compartmentalization.

Makhsous, Negar / Goya, Stephanie / Avendaño, Carlos / Rupp, Jason / Kuypers, Jane / Jerome, Keith R / Boeckh, Michael / Waghmare, Alpana / Greninger, Alexander L

bioRxiv : the preprint server for biology

2023

Abstract: Background: Human rhinovirus (HRV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how HRV evolves within hosts during infection. ...

Abstract	Background: Human rhinovirus (HRV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how HRV evolves within hosts during infection. Methods: We sequenced HRV complete genomes from 12 hematopoietic cell transplant patients with prolonged infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL) specimens. Metagenomic (mNGS) and amplicon-based NGS were used to study the emergence and evolution of intra-host single nucleotide variants (iSNVs). Results: Identical HRV intra-host populations in matched NW and BAL specimens indicated no genetic adaptation is required for HRV to progress from URT to LRT. Microbial composition between matched NW and BAL confirmed no cross-contamination during sampling procedure. Coding iSNVs were 2.3-fold more prevalent in capsid over non-structural genes, adjusted for length. iSNVs modeled onto HRV capsid structures were significantly more likely to be found in surface residues, but were not preferentially located in known HRV neutralizing antibody epitopes. Newly emergent, serotype-matched iSNV haplotypes from immunocompromised individuals from 2008-2010 could be detected in Seattle-area community HRV sequences from 2020-2021. Conclusion: HRV infections in immunocompromised hosts can progress from URT to LRT with no specific evolutionary requirement. Capsid proteins carry the highest variability and emergent mutations can be detected in other, including future, HRV sequences.
Language	English
Publishing date	2023-05-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.11.540440
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Article ; Online: The impact of pre-transplant respiratory virus detection on post-transplant outcomes in children undergoing hematopoietic cell transplantation.

Kim, Sara Ruth / Nordlander, Anna / Xie, Hu / Kim, Yae-Jean / Ogimi, Chikara / Thakar, Monica S / Leisenring, Wendy / Englund, Janet A / Boeckh, Michael / Waghmare, Alpana

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2024

Abstract: Background: Pre-transplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay due to high-risk RVs, we examined the impact of pre- ...

Abstract	Background: Pre-transplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay due to high-risk RVs, we examined the impact of pre-transplant RV detection on transplant outcomes in a pediatric HCT recipients. Methods: This retrospective cohort study included myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using RT-PCR, regardless of symptoms. Post-transplant outcomes included days alive and out of hospital (DAOH) and progression to lower respiratory tract infection (LRTI). Results: Among 310 patients, 134 had a RV detected in the 90 days prior to HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count less than 100/mm3, and HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus (HRV) as a virus type, and symptomatic pre-transplant upper respiratory tract infection (URTI) were associated with fewer DAOH. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to post-transplant LRTI with the same pre-transplant RV if the last positive PCR before HCT was ≤30 days compared to >30 days (p=0.007). Conclusion: In the setting of recommending HCT delay for high-risk RVs, symptomatic URTI, including HRV infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciae216
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Article ; Online: Respiratory viruses

Waghmare, Alpana / Englund, Janet A.

Pediatric Transplant and Oncology Infectious Diseases

Abstract: Respiratory viruses are commonly detected in both healthy and immunocompromised children. In most healthy children, respiratory viruses are associated with self-limited upper respiratory tract infections and are not accompanied by significant morbidity. ... ...

Abstract	Respiratory viruses are commonly detected in both healthy and immunocompromised children. In most healthy children, respiratory viruses are associated with self-limited upper respiratory tract infections and are not accompanied by significant morbidity. In immunocompromised hosts, including hematopoietic cell transplant recipients, solid organ transplant recipients, and oncology patients, respiratory viruses can be associated with significant clinical manifestations, including prolonged viral shedding, lower respiratory tract disease, the need for supplemental oxygen, late airflow obstruction, and even death. This chapter reviews the major respiratory viruses, including respiratory syncytial virus, human metapneumovirus, influenza, parainfluenza viruses, human rhinoviruses, and human coronaviruses. Other viruses can manifest as pulmonary infection; however, these viruses are discussed elsewhere (see Chapter 17 for discussion of cytomegalovirus and Chapter 22 for discussion of adenoviruses).
Keywords	covid19
Publisher	Elsevier; PMC
Document type	Article ; Online
DOI	10.1016/b978-0-323-64198-2.00030-0
Database	COVID19

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