Mechanically Ventilated Patients Shed High-Titer Live Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for Extended Periods From Both the Upper and Lower Respiratory Tract
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Abstract
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 prospectively examined upper and lower airway respiratory secretions for both viral RNA and infectious virions in mechanically ventilated patients admitted to the intensive care unit (ICU) of the University Hospital of Wales. Samples were taken from the oral cavity (saliva), oropharynx (subglottic aspirate), or lower respiratory tract (nondirected bronchoalveolar lavage [NBAL] or bronchoalveolar lavage [BAL]) and analyzed by both quantitative PCR (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 titers of live virus were higher in subglottic aspirates (4.5 × 107) than in saliva (2.2 × 106) or BAL/NBAL (8.5 × 106) and reached >108 PFU/mL in some samples. The longest duration of shedding was 98 days, while most patients (14/25) shed live virus for ≥20 days.
Conclusions
ICU patients infected with SARS-CoV-2 can shed high titers 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 personal protective equipment, and undertaking potential aerosol-generating procedures.
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SciScore for 10.1101/2021.12.27.21268312: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Board, REC board Yorkshire & The Humber - Bradford Leeds Research Ethics Committee). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Plaque assays utilised Vero E6, a gift from the University of Glasgow/MRC Centre for Virology, UK. Vero E6suggested: RRID:CVCL_XD71)6-fold serial dilutions of each sample type were used to infect the Vero E6 ACE2/TMPRSS2 cells for 1 h at 37 □C with rocking. Vero E6 ACE2/TMPRSS2suggested: NoneRecombinant DNA Sentences Resources Gene copy load was quantified using an E-gene control plasmid … SciScore for 10.1101/2021.12.27.21268312: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Board, REC board Yorkshire & The Humber - Bradford Leeds Research Ethics Committee). Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Plaque assays utilised Vero E6, a gift from the University of Glasgow/MRC Centre for Virology, UK. Vero E6suggested: RRID:CVCL_XD71)6-fold serial dilutions of each sample type were used to infect the Vero E6 ACE2/TMPRSS2 cells for 1 h at 37 □C with rocking. Vero E6 ACE2/TMPRSS2suggested: NoneRecombinant DNA Sentences Resources Gene copy load was quantified using an E-gene control plasmid (pEX-A128-nCoV_E_Sarbeco, Eurofins Genomics, Germany). pEX-A128-nCoV_E_Sarbecosuggested: NoneResults from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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