SARS-CoV-2 shedding dynamics across the respiratory tract, sex and disease severity for adult and pediatric COVID-19

Chen, Paul Z.; Bobrovitz, Niklas; Premji, Zahra; Fisman, David N.; Gu, Frank

doi:10.1101/2021.02.17.21251926

Cited by 16 publications

(22 citation statements)

References 75 publications

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“…The forced exhalation approach appeared much less sensitive (i.e. 22% positive agreement) in this student group (average ~22 years old, ambulatory, upright position during sampling) as compared to the first study on a cohort of hospitalized patients (average ~62 years old, in-patient, recumbent position during sampling), suggesting a possible effect of age, sampling position, a lower respiratory tract infection prompting admission, or another covariate not assessed within this study 19,20 . The observed difference in positive percentage agreement between breathing techniques (22% vs 74%) is striking and warrants further research.…”

Section: Sars-cov-2 Detection In Exhaled Particlesmentioning

confidence: 57%

Molecular Detection of SARS-Cov-2 in Exhaled Breath Using a Portable Sampler

Stakenborg¹,

Raymenants

Taher³

et al. 2021

Preprint

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The SARS-CoV-2 pandemic has highlighted the need for improved technologies to help control the spread of contagious pathogens. While rapid point-of-need testing plays a key role in strategies to rapidly identify and isolate infectious patients, a cornerstone for any disease-control strategy, current test approaches have significant shortcomings related to assay limitations and sample type. Direct quantification of viral shedding in exhaled particles may offer a better rapid testing approach, since SARS-CoV-2 is believed to spread mainly by aerosols. It potentially measures contagiousness directly, the sample is easy to obtain, its production can be standardized between patients, and the limited sample volume lends itself to a fast and sensitive analysis. In view of these benefits, we developed and tested an approach where exhaled particles are efficiently sampled using inertial impaction in a micromachined silicon chip, followed by an in-situ RT-qPCR molecular assay to detect SARS-CoV-2 shedding. We demonstrate that sampling subjects using a one-minute breathing protocol, yields sufficient viral RNA to detect infections with a sensitivity comparable to standard sampling methods. A longitudinal study revealed clear differences in the temporal dynamics of viral load for nasopharyngeal swab, saliva, breath, and antigen tests. Overall, after an infection, the breath-based test is the first to consistently report a negative result, putatively signaling the end of contagiousness and further emphasizing the potential of this tool to help manage the spread of airborne respiratory infections.

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Section: Sars-cov-2 Detection In Exhaled Particlesmentioning

confidence: 57%

Molecular Detection of SARS-Cov-2 in Exhaled Breath Using a Portable Sampler

Stakenborg¹,

Raymenants

Taher³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…As severe COVID-19 is associated with high, persistent SARS-CoV-2 shedding in the lower respiratory tract (P. Z. Chen et al, 2021) and small particles are typically generated there (Johnson et al, 2011), severe cases may also expel higher quantities of virions via smaller aerosols.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols

Chen

Bobrovitz

Premji

et al. 2021

eLife

Self Cite

133

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Background: Which virological factors mediate overdispersion in the transmissibility of emerging viruses remains a longstanding question in infectious disease epidemiology.Methods: Here, we use systematic review to develop a comprehensive dataset of respiratory viral loads (rVLs) of SARS-CoV-2, SARS-CoV-1 and influenza A(H1N1)pdm09. We then comparatively meta-analyze the data and model individual infectiousness by shedding viable virus via respiratory droplets and aerosols.Results: The analyses indicate heterogeneity in rVL as an intrinsic virological factor facilitating greater overdispersion for SARS-CoV-2 in the COVID-19 pandemic than A(H1N1)pdm09 in the 2009 influenza pandemic. For COVID-19, case heterogeneity remains broad throughout the infectious period, including for pediatric and asymptomatic infections. Hence, many COVID-19 cases inherently present minimal transmission risk, whereas highly infectious individuals shed tens to thousands of SARS-CoV-2 virions/min via droplets and aerosols while breathing, talking and singing. Coughing increases the contagiousness, especially in close contact, of symptomatic cases relative to asymptomatic ones. Infectiousness tends to be elevated between 1-5 days post-symptom onset.Conclusions: Intrinsic case variation in rVL facilitates overdispersion in the transmissibility of emerging respiratory viruses. Our findings present considerations for disease control in the COVID-19 pandemic as well as future outbreaks of novel viruses.Funding: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program, NSERC Senior Industrial Research Chair program and the Toronto COVID-19 Action Fund.

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“…Nevertheless, the well-defined cohort of participants we studied allowed for direct, minimally-invasive access to the LRT for vRNA quantification in ETA specimens, which are routinely obtained for clinical microbiology studies in COVID-19 subjects, as opposed to invasive bronchoscopic samples. We did not analyze upper respiratory tract vRNA levels, because our focus was to examine LRT viral burden and its relationship with plasma vRNA levels in patients with severe disease, and viral shedding in severe COVID-19 has been reported to be prolonged in the lower as compared to the upper respiratory tract [11]. Our findings also highlight the importance of analyzing the timing of measurement of vRNA biomarkers in relation to the clinical timeline of COVID-19, given the rapid and dynamic decline of vRNA levels in both the LRT and blood compartments.…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

Plasma SARS-CoV-2 RNA levels as a biomarker of lower respiratory tract SARS-CoV-2 infection in critically ill patients with COVID-19

Jacobs

Naqvi

Shah

et al. 2022

Preprint

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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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SARS-CoV-2 shedding dynamics across the respiratory tract, sex and disease severity for adult and pediatric COVID-19

Cited by 16 publications

References 75 publications

Molecular Detection of SARS-Cov-2 in Exhaled Breath Using a Portable Sampler

Molecular Detection of SARS-Cov-2 in Exhaled Breath Using a Portable Sampler

Heterogeneity in transmissibility and shedding SARS-CoV-2 via droplets and aerosols

Plasma SARS-CoV-2 RNA levels as a biomarker of lower respiratory tract SARS-CoV-2 infection in critically ill patients with COVID-19

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