Reliability of self-sampling for accurate assessment of respiratory virus viral and immunologic kinetics.
Author(s): Waghmare A, Krantz EM, Baral S, Vasquez E, Loeffelholz T, Chung EL, Pandey U, Kuypers J, Duke ER, Jerome KR, Greninger AL, Reeves DB, Hladik F, Cardozo-Ojeda EF, Boeckh M, Schiffer JT
Publication: J Infect Dis, 2020, Vol. , Page
PubMed ID: 32710762 PubMed Review Paper? No
Purpose of Paper
This paper compared respiratory viral detection between self-collected flocked swabs and foam swabs and between specimens obtained from the left versus right nostril. The effect of collection timing on virus detection and cytokine levels was also investigated.
Conclusion of Paper
Viral DNA was detected in specimens from 11 of 15 patients with concordance found between swab types for 22 of 30 specimens and between nostrils for 22 of 30 patients. Importantly, discordance between swab types only occurred in cases with viral loads <4 log10 viral copies per mL.
The pattern of viral load and cytokines showed consistency between days with viral load declining as the symptoms decreased. Cytokine levels in human rhinovirus (HRV)-positive specimens were strongly correlated among cytokines with the same cellular origin (T-cell, macrophage, or epithelial derived) with only weak correlations noted between HRV-positive specimens and cytotoxic T-cell response cytokines. For HRV-positive patients, there were three distinct cytokine responses with all patients displaying the least inflammatory signature at some time-points but only two patients showing the most inflammatory signature at any time-point.
Studies
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Study Purpose
This study compared respiratory viral detection between self-collected flocked swabs and foam swabs and between specimens obtained from the left versus right nostril. Fifteen patients with symptoms of a respiratory infection for less than 3 days self-collected specimens from each nostril using Copan flocked swabs or Puritan foam swabs. An hour after the first collection, patients self-collected specimens from each nostril using the other swab type. Swabs were vortexed in buffer and stored at -80°C until virus detection using a multiplex real-time PCR assay for 11 respiratory viruses including adenovirus A-F, human rhinovirus (HRV), influenza A and B, parainfluenza viruses (PIV) 1-4, human coronavirus, bocavirus (BoV), respiratory syncytial virus (RSV), and human metapneumovirus (MPV).
Summary of Findings:
Viral RNA was detected in specimens from 11 of 15 patients. Concordance between swab types from the same nostril was obtained for 22 or 30 specimens. Viruses were detected in the foam swab but not the flocked swab in five cases (one HRV, four coronavirus) and in the flocked but not foam swab in three cases (all coronavirus). Importantly, the discordant cases all had viral loads <4 log10 viral copies per mL. Interestingly, there was discordance between nostrils in 8 of 30 specimens (5 detected only in right, 3 only in left) and viral levels tended to differ between the nostrils. Most patients preferred foam to flocked swabs.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Pneumonia/Respiratory Infection
Platform:
Analyte Technology Platform RNA Real-time qRT-PCR Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Acquisition Biospecimen location Left nostril
Right nostril
Biospecimen Acquisition Method of cell acquisition Foam swab
Flocked swab
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Study Purpose
This study examined nine patients with symptoms of a respiratory infection for less than 3 days. Self-collected specimens from each nostril were obtained using Puritan foam swabs daily for 14 days or, if symptoms persisted, until they resolved. Swabs were vortexed in buffer and stored at -80°C until virus detection using a multiplex real-time PCR assay for 11 respiratory viruses including adenovirus A-F, HRV, influenza A and B, PIV 1-4, coronavirus, BoV, RSV, and MPV. Cytokines were quantified using the electrochemiluminescence-based Mesoscale Discovery Assay.
Summary of Findings:
Over the course of sampling, viruses were detected in all nine patients with four patients having HRV, one having coronavirus, one each having only RSV, co-infection with adenovirus and HRV, co-infection with coronavirus and HRV, and co-infection with adenovirus and MPV. The pattern of viral load showed consistency between days with viral load declining as the symptoms decreased. Similarly, levels of interleukin (IL)-2, IL-4, IL-5, IL-10, IL-13, IL-17A, and eotaxin were consistent between patients and over the time course, indicating reliability of the technique. Further, levels of cytokines changed over the viral time-course. Cytokine levels in HRV-positive specimens were strongly correlated among cytokines with the same cellular origin (T-cell, macrophage, or epithelial derived) with only weak correlations noted between HRV and cytotoxic T-cell response cytokines. For HRV-positive patients, there were three distinct cytokine responses with specimens from all six patients with HRV displaying the least inflammatory signature at some time-points, five patients displaying the moderate inflammatory signature at some time points, and only two patients showing the most inflammatory signature at any time-point. The cytokine responses in RSV and MPV patients did not form as distinct clusters.
Biospecimens
Preservative Types
- Frozen
Diagnoses:
- Pneumonia/Respiratory Infection
Platform:
Analyte Technology Platform Protein Electroimmunoassay RNA Real-time qRT-PCR Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Preaquisition Diagnosis/ patient condition HRV
RSV
MPV
Biospecimen Acquisition Time of biospecimen collection Days 1-14