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Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant Recipients: Risk Factors and Viral Genome Evolution.

Abstract Recent data suggest that human coronavirus (HCoV) pneumonia is associated with significant mortality in hematopoietic cell transplant (HCT) recipients. Investigation of risk factors for prolonged shedding and intrahost genome evolution may provide critical information for development of novel therapeutics.
PMID
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Authors

Mayor MeshTerms

Hematopoietic Stem Cell Transplantation

Virus Shedding

Keywords

genome evolution

hematopoietic cell transplant

human coronavirus

shedding

whole genome sequencing

Journal Title the journal of infectious diseases
Publication Year Start




PMID- 28838146
OWN - NLM
STAT- MEDLINE
DA  - 20170825
DCOM- 20170907
LR  - 20170907
IS  - 1537-6613 (Electronic)
IS  - 0022-1899 (Linking)
VI  - 216
IP  - 2
DP  - 2017 Jul 15
TI  - Prolonged Shedding of Human Coronavirus in Hematopoietic Cell Transplant
      Recipients: Risk Factors and Viral Genome Evolution.
PG  - 203-209
LID - 10.1093/infdis/jix264 [doi]
AB  - Background: Recent data suggest that human coronavirus (HCoV) pneumonia is
      associated with significant mortality in hematopoietic cell transplant (HCT)
      recipients. Investigation of risk factors for prolonged shedding and intrahost
      genome evolution may provide critical information for development of novel
      therapeutics. Methods: We retrospectively reviewed HCT recipients with HCoV
      detected in nasal samples by polymerase chain reaction (PCR). HCoV strains were
      identified using strain-specific PCR. Shedding duration was defined as time
      between first positive and first negative sample. Logistic regression analyses
      were performed to evaluate factors for prolonged shedding (>/=21 days).
      Metagenomic next-generation sequencing (mNGS) was conducted when >/=4 samples
      with cycle threshold values of <28 were available. Results: Seventeen of 44
      patients had prolonged shedding. Among 31 available samples, 35% were OC43, 32%
      were NL63, 19% were HKU1, and 13% were 229E; median shedding duration was similar
      between strains (P = .79). Bivariable logistic regression analyses suggested that
      high viral load, receipt of high-dose steroids, and myeloablative conditioning
      were associated with prolonged shedding. mNGS among 5 subjects showed
      single-nucleotide polymorphisms from OC43 and NL63 starting 1 month following
      onset of shedding. Conclusions: High viral load, high-dose steroids, and
      myeloablative conditioning were associated with prolonged shedding of HCoV in HCT
      recipients. Genome changes were consistent with the expected molecular clock of
      HCoV.
FAU - Ogimi, Chikara
AU  - Ogimi C
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Department of Pediatrics, University of Washington.
AD  - Pediatric Infectious Diseases Division, Seattle Children's Hospital.
FAU - Greninger, Alexander L
AU  - Greninger AL
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Department of Laboratory Medicine, University of Washington.
FAU - Waghmare, Alpana A
AU  - Waghmare AA
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Department of Pediatrics, University of Washington.
AD  - Pediatric Infectious Diseases Division, Seattle Children's Hospital.
FAU - Kuypers, Jane M
AU  - Kuypers JM
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Department of Laboratory Medicine, University of Washington.
FAU - Shean, Ryan C
AU  - Shean RC
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Department of Laboratory Medicine, University of Washington.
FAU - Xie, Hu
AU  - Xie H
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center.
FAU - Leisenring, Wendy M
AU  - Leisenring WM
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center.
AD  - Biostatistics.
FAU - Stevens-Ayers, Terry L
AU  - Stevens-Ayers TL
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
FAU - Jerome, Keith R
AU  - Jerome KR
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Department of Laboratory Medicine, University of Washington.
FAU - Englund, Janet A
AU  - Englund JA
AD  - Department of Pediatrics, University of Washington.
AD  - Pediatric Infectious Diseases Division, Seattle Children's Hospital.
FAU - Boeckh, Michael
AU  - Boeckh M
AD  - Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center.
AD  - Medicine, University of Washington, Seattle, Washington.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Infect Dis
JT  - The Journal of infectious diseases
JID - 0413675
RN  - 0 (Steroids)
SB  - AIM
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Coronavirus/classification/*genetics
MH  - Coronavirus Infections/*epidemiology
MH  - Female
MH  - Genome, Viral
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Respiratory Tract Infections/*epidemiology/virology
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Steroids/adverse effects
MH  - Viral Load
MH  - *Virus Shedding
MH  - Young Adult
OTO - NOTNLM
OT  - genome evolution
OT  - hematopoietic cell transplant
OT  - human coronavirus
OT  - shedding
OT  - whole genome sequencing
EDAT- 2017/08/26 06:00
MHDA- 2017/09/08 06:00
CRDT- 2017/08/26 06:00
PHST- 2017/04/05 [received]
PHST- 2017/05/26 [accepted]
AID - 3858443 [pii]
AID - 10.1093/infdis/jix264 [doi]
PST - ppublish
SO  - J Infect Dis. 2017 Jul 15;216(2):203-209. doi: 10.1093/infdis/jix264.