scholarly journals Disparate evolution of virus populations in upper and lower airways of mechanically ventilated patients

2019 ◽  
Author(s):  
Björn F. Koel ◽  
Frank van Someren Gréve ◽  
René M. Vigeveno ◽  
Maarten Pater ◽  
Colin A. Russell ◽  
...  

AbstractIn routine surveillance and diagnostic testing, influenza virus samples are typically collected only from the upper respiratory tract (URT) due to the invasiveness of sample collection from the lower airways. Very little is known about virus variation in the lower respiratory tract (LRT) and it remains unclear if the virus populations at different sites of the human airways may develop to have divergent genetic signatures. We used deep sequencing of serially obtained matched nasopharyngeal swabs and endotracheal aspirates from four mechanically ventilated patients with influenza A/H3N2 infections. A physical barrier separating both compartments of the respiratory tract introduced as part of the medical procedures enabled us to track and compare the genetic composition of the virus populations during isolated evolution in the same host. Amino acid variants reaching majority proportions emerged during the course of infection in both nasopharyngeal swabs and endotracheal aspirates, and amino acid variation was observed in all influenza virus proteins. Genetic variation of the virus populations differed between the URT and LRT and variants were frequently uniquely present in either URT or LRT virus populations of a patient. These observations indicate that virus populations in spatially distinct parts of the human airways may follow different evolutionary trajectories. Selectively sampling from the URT may therefore fail to detect potentially important emerging variants.ImportanceInfluenza viruses are rapidly mutating pathogens that easily adapt to changing environments. Although advances in sequencing technology make it possible to identify virus variants at very low proportions of the within-host virus population, several aspects of intrahost viral evolution have not been studied because sequentially collected samples and samples from the lower respiratory tract are not routinely obtained for influenza surveillance or clinical diagnostic purposes. Importantly, how virus populations evolve in different parts of the human respiratory tract remains unknown. Here we used serial clinical specimens collected from mechanically ventilated influenza patients to compare how virus populations develop in the upper and lower respiratory tract. We show that virus populations in the upper and lower respiratory tract may evolve along distinct evolutionary pathways, and that current sampling and surveillance regimens likely capture only part of the complete intrahost virus variation.

2003 ◽  
Vol 29 (7) ◽  
pp. 1062-1068 ◽  
Author(s):  
René Robert ◽  
Ghislaine Grollier ◽  
Jean-Pierre Frat ◽  
Cendrine Godet ◽  
Michèle Adoun ◽  
...  

2003 ◽  
Vol 29 (11) ◽  
pp. 2107-2107
Author(s):  
Ren� Robert ◽  
Ghislaine Grollier ◽  
Jean-Pierre Frat ◽  
Cendrine Godet ◽  
Mich�le Adoun ◽  
...  

2021 ◽  
Author(s):  
Zack Saud ◽  
Mark J PONSFORD ◽  
Kirsten Bentley ◽  
Jade Cole ◽  
Manish Pandey ◽  
...  

Background SARS-CoV-2 infection can lead to severe acute respiratory distress syndrome needing intensive care admission and may lead to death. As a virus that transmits by respiratory droplets and aerosols, determining the duration of viable virus shedding from the respiratory tract is critical for patient prognosis, and informs infection control measures both within healthcare settings and the public domain. Methods We examined upper and lower airway respiratory secretions for both viral RNA and infectious virions in mechanically ventilated patients admitted to the intensive care unit of the University Hospital of Wales. Samples were taken from the oral cavity (saliva), oropharynx (sub-glottic aspirate), or lower respiratory tract (non-directed bronchoalveolar lavage (NBL) or bronchoalveolar lavage (BAL)) and analyzed by both qPCR and plaque assay. Results 117 samples were obtained from 25 patients. qPCR showed extremely high rates of positivity across all sample types, however live virus was far more common in saliva (68%) than in BAL/NBAL (32%). Average titres of live virus were higher in subglottic aspirates (4.5x10^7) than in saliva (2.2x10^6) or BAL/NBAL (8.5x10^6), and reached >10^8 PFU/ml in some samples. The longest duration of shedding was 98 days, while the majority of patients (14/25) shed live virus for 20 days or longer. Conclusions Intensive care unit patients infected with SARS-CoV-2 can shed high titres of virus both in the upper and lower respiratory tract, and tend to be prolonged shedders. This information is important for decision making around cohorting patients, de-escalation of PPE, and undertaking potential aerosol generating procedures.


2022 ◽  
Author(s):  
Jana Jacobs ◽  
Asma Naqvi ◽  
Faraaz Shah ◽  
Valerie Boltz ◽  
Mary Kearney ◽  
...  

Plasma SARS-CoV-2 viral RNA (vRNA) levels are predictive of COVID-19 outcomes in hospitalized patients, but whether plasma vRNA reflects lower respiratory tract (LRT) vRNA levels is unclear. We compared plasma and LRT vRNA levels in simultaneously collected longitudinal samples from mechanically-ventilated patients with COVID-19. LRT and plasma vRNA levels were strongly correlated at first sampling (r=0.83, p<10-8) and then declined in parallel except in non-survivors who exhibited delayed vRNA clearance in LRT samples. Plasma vRNA measurement may offer a practical surrogate of LRT vRNA burden in critically ill patients, especially early in severe disease.


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