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 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 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 1465. Age-Dependent Interactions Among Clinical Characteristics, Viral Loads and Disease Severity in Young Children with Respiratory Syncytial Virus Infection (RSV) Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S734-S735
Author(s):  
Helena Brenes-Chacon ◽  
Cristina Garcia-Maurino ◽  
Melissa Moore-Clingenpeel ◽  
Sara Mertz ◽  
Fang Ye ◽  
...  
Keyword(s):  
Young Children ◽  
Disease Severity ◽  
Age Groups ◽  
Panel Member ◽  
Signs And Symptoms ◽  
Research Support ◽  
Review Panel ◽  
Viral Loads ◽  
Age Dependent ◽  
Rsv Infection

Abstract Background Differences in clinical presentation and viral loads according to age in young children with RSV, and their correlation with disease severity are poorly defined. The aim of this study was to define age-dependent the differences in demographic, clinical factors and viral loads between children &lt; 2 years of age with mild RSV infection evaluated as outpatients versus those hospitalized with severe RSV infection. Figure 1. Sign and Symptoms according to disease severity and age in infants with RSV infection. Most relevant signs and symptoms were stratified in outpatients (orange) vs inpatients (blue) by age in (A) &lt; 3 months, (B) between 3 and 6 months, and (C) &gt; 6 to 24 months of age. The Y axis represents the signs and symptoms in the two disease severity groups and the X axis the frequency of that specific symptom (%). Numbers next to bars represent the exact number of patients with that specific sign/symptom. Comparisons by Fisher exact test. Symbol (*) indicate significant 2-sided p values Figure 2. Viral load differences according to age in infants with RSV infection. The Y axis represents RSV loads in log10 copies/mL and the X axis differences in viral loads in outpatients (orange) and inpatients (blue) in the three age groups. Comparisons by Mann Whitney test. Methods Previously healthy children &lt; 2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and nasopharyngeal swabs were obtained for RSV typing and quantitation by real-time PCR. Patients were stratified by age (0-&lt; 3, 3-6, and &gt;6-24 months) and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. Results From 2014-2018 we enrolled 534 children with RSV infection: 130 outpatients and 404 inpatients. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than inpatient in the three age groups (Fig 1). Wheezing was more frequent in outpatients of older age (&gt;3 months) than in inpatients (p&lt; 0.01), while fever was more common in inpatients that outpatients (p&lt; 0.01) and increased with age (Fig 2). Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants &gt;3 months, and higher RSV loads in children &gt;6-24 months were independently associated with reduced disease severity. Conclusion Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

scholarly journals The Role of the Respiratory Microbiome and Viral Presence in Lower Respiratory Tract Infection Severity in the First Five Years of Life

2021 ◽  
Vol 9 (7) ◽  
pp. 1446
Author(s):  
Ivo Hoefnagels ◽  
Josephine van de Maat ◽  
Jeroen J.A. van Kampen ◽  
Annemarie van Rossum ◽  
Charlie Obihara ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Disease Severity ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Pediatric Population ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Detection Rates ◽  
Tract Infections ◽  
Respiratory Microbiome

Lower respiratory tract infections (LRTIs) in children are common and, although often mild, a major cause of mortality and hospitalization. Recently, the respiratory microbiome has been associated with both susceptibility and severity of LRTI. In this current study, we combined respiratory microbiome, viral, and clinical data to find associations with the severity of LRTI. Nasopharyngeal aspirates of children aged one month to five years included in the STRAP study (Study to Reduce Antibiotic prescription in childhood Pneumonia), who presented at the emergency department (ED) with fever and cough or dyspnea, were sequenced with nanopore 16S-rRNA gene sequencing and subsequently analyzed with hierarchical clustering to identify respiratory microbiome profiles. Samples were also tested using a panel of 15 respiratory viruses and Mycoplasma pneumoniae, which were analyzed in two groups, according to their reported virulence. The primary outcome was hospitalization, as measure of disease severity. Nasopharyngeal samples were isolated from a total of 167 children. After quality filtering, microbiome results were available for 54 children and virology panels for 158 children. Six distinct genus-dominant microbiome profiles were identified, with Haemophilus-, Moraxella-, and Streptococcus-dominant profiles being the most prevalent. However, these profiles were not found to be significantly associated with hospitalization. At least one virus was detected in 139 (88%) children, of whom 32.4% had co-infections with multiple viruses. Viral co-infections were common for adenovirus, bocavirus, and enterovirus, and uncommon for human metapneumovirus (hMPV) and influenza A virus. The detection of enteroviruses was negatively associated with hospitalization. Virulence groups were not significantly associated with hospitalization. Our data underlines high detection rates and co-infection of viruses in children with respiratory symptoms and confirms the predominant presence of Haemophilus-, Streptococcus-, and Moraxella-dominant profiles in a symptomatic pediatric population at the ED. However, we could not assess significant associations between microbiome profiles and disease severity measures.

scholarly journals Biomarkers in COPD – Challenging, Real or Illusive

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 351-363
Author(s):  
Radostina V. Cherneva ◽  
Dimitar T. Kostadinov
Keyword(s):  
Respiratory Tract ◽  
Disease Severity ◽  
Biological Samples ◽  
Biological Sample ◽  
Respiratory Medicine ◽  
European Medicines Agency ◽  
Tissue Sampling ◽  
Huge Amount ◽  
Biomarker Research

Abstract Biomarker research in COPD is becoming the most rapidly progressing sphere in respiratory medicine. Although “omics” generate a huge amount of biomarkers, fibrinogen is the only one validated by the European Medicines Agency. Thousands of studies analyzing different biological samples from the respiratory tract, collected in different ways, using various kits and techniques are generating more and more data, rendering biomarkers very confusing rather than having practical value. It seems that in order to be applicable and validated, biomarkers should be analysed in an accurately described cohort of patients, homogeneous in disease severity and activity. As COPD has multiple mechanisms of pathobiology it raises the issue of which is the most appropriate biological sample reflecting each of them. Unified criteria for tissue sampling, validated kits for respiratory tract probes and standardized technologies should be announced. The review presents the biomarkers that are currently validated and raises the problem of standardization.

scholarly journals SARS-CoV-2 infection and persistence throughout the human body and brain

2021 ◽  
Author(s):  
Daniel Chertow ◽  
Sydney Stein ◽  
Sabrina Ramelli ◽  
Alison Grazioli ◽  
Joon-Yong Chung ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Human Body ◽  
Symptom Onset ◽  
Acute Infection ◽  
Systemic Infection ◽  
The Body ◽  
Viral Clearance ◽  
Cell Type ◽  
Cell Type Specificity ◽  
The Brain

Abstract COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14. We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple extrapulmonary tissues early in infection. Further, we detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.

scholarly journals Asymptomatic COVID-19 Adult Outpatients identified as Significant Viable SARS-CoV-2 Shedders 

2021 ◽  
Author(s):  
Marie Glenet ◽  
Anne-Laure Lebreil ◽  
Laetitia Heng ◽  
Yohan N’Guyen ◽  
Ittah Meyer ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Control Measures ◽  
Upper Respiratory Tract ◽  
Rna Detection ◽  
Viral Loads ◽  
Infection Control Measures ◽  
Infected Adult ◽  
Asymptomatic Adult ◽  
Upper Respiratory ◽  
Kinetics Of

Abstract Differential kinetics of RNA loads and infectious viral levels in the upper respiratory tract between asymptomatic and symptomatic SARS-CoV-2 infected adult outpatients remain unclear limiting recommendations that may guide clinical management, infection control measures and occupational health decisions. In the present investigation, 496 (2.5%) of 17,911 French adult outpatients were positive for an upper respiratory tract SARS-CoV-2 RNA detection by a quantitative RT-PCR assay, of which 180 (36.3%) were COVID-19 asymptomatic. Of these adult asymptomatic viral shedders, 84.4% had mean to high RNA viral loads (Ct values<30) which median value was significantly higher than that observed in symptomatic subjects (P=0.029), and 50.6% were positive by cell culture assays of their upper respiratory tract specimens. Our findings indicate that COVID-19 asymptomatic adult outpatients are significant viable SARS-CoV-2 shedders in their upper respiratory tract playing a major potential role as SARS-CoV-2 transmitters in various epidemiological transmission chains, promoting COVID-19 resurgence in populations.

Sign in / Sign up

Export Citation Format

Share Document