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

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Paul Z Chen ◽  
Niklas Bobrovitz ◽  
Zahra Premji ◽  
Marion Koopmans ◽  
David N Fisman ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Age Groups ◽  
Prognostic Indicator ◽  
Individual Case ◽  
Engineering Research ◽  
Case Characteristics ◽  
Kinetics Of ◽  
Do So

Background:Previously, we conducted a systematic review and
 analyzed the respiratory kinetics of SARS-CoV-2 (P. Z. Chen et al., 2021). How age, sex and
 COVID-19 severity interplay to influence the shedding dynamics of SARS-CoV-2, however,
 remains poorly understood.Methods:We updated our systematic
 dataset, collected individual case characteristics and conducted stratified analyses of
 SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) across
 COVID-19 severity, sex and age groups (aged 0 to 17 years, 18 to 59 years, and 60 years or
 older).Results:The systematic dataset included 1,266 adults
 and 136 children with COVID-19. Our analyses indicated that high, persistent LRT shedding of
 SARS-CoV-2 characterized severe COVID-19 in adults. Severe cases tended to show slightly
 higher URT shedding post-symptom onset, but similar rates of viral clearance, when compared
 to nonsevere infections. After stratifying for disease severity, sex and age (including
 child vs. adult) were not predictive of respiratory shedding. The estimated accuracy for
 using LRT shedding as a prognostic indicator for COVID-19 severity was up to 81%, whereas it
 was up to 65% for URT shedding.Conclusions:Virological
 factors, especially in the LRT, facilitate the pathogenesis of severe COVID-19. Disease
 severity, rather than sex or age, predict SARS-CoV-2 kinetics. LRT viral load may
 prognosticate COVID-19 severity in patients before the timing of deterioration, and should
 do so more accurately than URT viral load.Funding:Natural
 Sciences and Engineering Research Council of Canada (NSERC) DiscoveryGrant, NSERC Senior
 Industrial Research Chair and the Toronto COVID-19 Action Fund.

scholarly journals SARS-CoV-2 Shedding Dynamics Across the Respiratory Tract, Sex, and Disease Severity for Adult and Pediatric COVID-19

2021 ◽  
Author(s):  
Paul Z. Chen ◽  
Niklas Bobrovitz ◽  
Zahra Premji ◽  
Marion Koopmans ◽  
David N. Fisman ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Disease Severity ◽  
Symptom Onset ◽  
Web Of Science ◽  
Limited Data ◽  
Clear Trend ◽  
Engineering Research ◽  
Age Cohorts ◽  
Viral Loads ◽  
Case Characteristics

BackgroundSARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) remain unclear.ObjectiveTo analyze SARS-CoV-2 shedding dynamics across COVID-19 severity, the respiratory tract, sex and age cohorts (aged 0 to 17 years, 18 to 59 years, and 60 years or older).DesignSystematic review and pooled analyses.SettingMEDLINE, EMBASE, CENTRAL, Web of Science Core Collection, medRxiv and bioRxiv were searched up to 20 November 2020.ParticipantsThe systematic dataset included 1,266 adults and 136 children with COVID-19.MeasurementsCase characteristics (COVID-19 severity, age and sex) and quantitative respiratory viral loads (rVLs).ResultsIn the URT, adults with severe COVID-19 had higher rVLs at 1 DFSO than adults (P = 0.005) or children (P = 0.017) with nonsevere illness. Between 1-10 DFSO, severe adults had comparable rates of SARS-CoV-2 clearance from the URT as nonsevere adults (P = 0.479) and nonsevere children (P = 0.863). In the LRT, severe adults showed higher post-symptom-onset rVLs than nonsevere adults (P = 0.006). In the analyzed period (4-10 DFSO), severely affected adults had no significant trend in SARS-CoV-2 clearance from LRT (P = 0.105), whereas nonsevere adults showed a clear trend (P < 0.001). After stratifying for disease severity, sex and age (including child vs. adult) were not predictive of the duration of respiratory shedding.LimitationLimited data on case comorbidities and few samples in some cohorts.ConclusionHigh, persistent LRT shedding of SARS-CoV-2 characterized severe COVID-19 in adults. After symptom onset, severe cases tended to have higher URT shedding than their nonsevere counterparts. Disease severity, rather than age or sex, predicted SARS-CoV-2 kinetics. LRT specimens should more accurately prognosticate COVID-19 severity than URT specimens.Primary Funding SourceNatural Sciences and Engineering Research Council.

scholarly journals Induction of interferon response by high viral loads at early stage infection may protect against severe outcomes in COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eric C. Rouchka ◽  
Julia H. Chariker ◽  
Brian Alejandro ◽  
Robert S. Adcock ◽  
Richa Singhal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Critical Factor ◽  
Interferon Response ◽  
Upper Respiratory Tract ◽  
Viral Loads ◽  
Antiviral Responses ◽  
Upper Respiratory

AbstractKey elements for viral pathogenesis include viral strains, viral load, co-infection, and host responses. Several studies analyzing these factors in the function of disease severity of have been published; however, no studies have shown how all of these factors interplay within a defined cohort. To address this important question, we sought to understand how these four key components interplay in a cohort of COVID-19 patients. We determined the viral loads and gene expression using high throughput sequencing and various virological methods. We found that viral loads in the upper respiratory tract in COVID-19 patients at an early phase of infection vary widely. While the majority of nasopharyngeal (NP) samples have a viral load lower than the limit of detection of infectious viruses, there are samples with an extraordinary amount of SARS-CoV-2 RNA and a high viral titer. No specific viral factors were identified that are associated with high viral loads. Host gene expression analysis showed that viral loads were strongly correlated with cellular antiviral responses. Interestingly, however, COVID-19 patients who experience mild symptoms have a higher viral load than those with severe complications, indicating that naso-pharyngeal viral load may not be a key factor of the clinical outcomes of COVID-19. The metagenomics analysis revealed that the microflora in the upper respiratory tract of COVID-19 patients with high viral loads were dominated by SARS-CoV-2, with a high degree of dysbiosis. Finally, we found a strong inverse correlation between upregulation of interferon responses and disease severity. Overall our study suggests that a high viral load in the upper respiratory tract may not be a critical factor for severe symptoms; rather, dampened antiviral responses may be a critical factor for a severe outcome from the infection.

scholarly journals Association between upper respiratory tract viral load, comorbidities, disease severity and outcome of patients with SARS-CoV-2 infection

2021 ◽  
Author(s):  
Helena C Maltezou ◽  
Vasilios Raftopoulos ◽  
Rengina Vorou ◽  
Kalliopi Papadima ◽  
Kassiani Mellou ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Disease Severity ◽  
High Viral Load ◽  
P Value ◽  
Upper Respiratory Tract ◽  
Limited Information ◽  
Symptomatic Disease ◽  
Viral Loads ◽  
Upper Respiratory

Abstract Background There is limited information on the association between upper respiratory tract (URT) viral loads, host factors, and disease severity in SARS-CoV-2 infected patients. Methods We studied 1,122 patients (mean age: 46 years) diagnosed by PCR. URT viral load, measured by PCR cycle threshold, was categorized as high, moderate or low. Results There were 336 (29.9%) patients with comorbidities; 309 patients (27.5%) had high, 316 (28.2%) moderate, and 497 (44.3%) low viral load. In univariate analyses, compared to patients with moderate or low viral load, patients with high viral load were older, had more often comorbidities, developed symptomatic disease, were intubated and died; in addition, patients with high viral load had longer stay in intensive care unit and longer intubation compared to patients with low viral load (p-values &lt;0.05 for all). Patients with chronic cardiovascular disease, hypertension, chronic pulmonary disease, immunosuppression, obesity and chronic neurological disease had more often high viral load (p-value&lt;0.05 for all). Multivariate analysis found that a high viral load was associated with COVID-19. The level of viral load was not associated with any other outcome. Conclusions URT viral load could be used to identify patients at higher risk for morbidity or severe outcome.

scholarly journals Kinetics of SARS-CoV-2 infection in the human upper and lower respiratory tracts and their relationship with infectiousness

2020 ◽  
Author(s):  
Ruian Ke ◽  
Carolin Zitzmann ◽  
Ruy M. Ribeiro ◽  
Alan S. Perelson
Keyword(s):  
Viral Load ◽  
Respiratory Tract ◽  
Dynamic Models ◽  
Target Cells ◽  
Upper Respiratory Tract ◽  
Viral Kinetics ◽  
Viral Loads ◽  
Viral Load Data ◽  
Upper Respiratory ◽  
Kinetics Of

SARS-CoV-2 is a human pathogen that causes infection in both the upper respiratory tract (URT) and the lower respiratory tract (LRT). The viral kinetics of SARS-CoV-2 infection and how they relate to infectiousness and disease progression are not well understood. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection in both the URT and LRT. We fit the models to viral load data from patients with likely infection dates known, we estimated that infected individuals with a longer incubation period had lower rates of viral growth, took longer to reach peak viremia in the URT, and had higher chances of presymptomatic transmission. We then developed a model linking viral load to infectiousness. We found that to explain the substantial fraction of transmissions occurring presymptomatically, the infectiousness of a person should depend on a saturating function of the viral load, making the logarithm of the URT viral load a better surrogate of infectiousness than the viral load itself. Comparing the roles of target-cell limitation, the innate immune response, proliferation of target cells and spatial infection in the LRT, we found that spatial dissemination in the lungs is likely to be an important process in sustaining the prolonged high viral loads. Overall, our models provide a quantitative framework for predicting how SARS-CoV-2 within-host dynamics determine infectiousness and represent a step towards quantifying how viral load dynamics and the immune responses determine disease severity.

Viral Load Dynamics and Clinical Disease Severity in Patients with SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Shufa Zheng ◽  
Jian Fan ◽  
Fei Yu ◽  
Baihuan Feng ◽  
Bin Lou ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Clinical Disease
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