Infectivity of asymptomatic versus symptomatic COVID-19

Sayampanathan, Andrew Arjun; Heng, Cheryl Sy; Pin, Phua Hwee; Pang, Junxiong; Leong, Teoh Yee; Lee, Vernon J.

doi:10.1016/s0140-6736(20)32651-9

Cited by 174 publications

(144 citation statements)

References 5 publications

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“…While our analyses did not account for virus infectivity, higher SARS-CoV-2 rVL is associated with a higher likelihood of culture positivity, from adults (15, 16) as well as children (36), and higher transmission risk (10). Hence, our results suggest that infectiousness increases with COVID-19 severity, concurring with epidemiological analyses (53, 54). They also suggest that adult and pediatric infections of similar severity have comparable infectiousness, reflecting epidemiological findings on age-based infectiousness (54-56).…”

Section: Discussionsupporting

confidence: 91%

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

Chen

Bobrovitz

Premji

et al. 2021

Preprint

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Background: SARS-CoV-2 shedding dynamics in the upper (URT) and lower respiratory tract (LRT) remain unclear. Objective: To 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). Design: Systematic review and pooled analyses. Setting: MEDLINE, EMBASE, CENTRAL, Web of Science Core Collection, medRxiv and bioRxiv were searched up to 20 November 2020. Participants: The systematic dataset included 1,266 adults and 136 children with COVID-19. Measurements: Case characteristics (COVID-19 severity, age and sex) and quantitative respiratory viral loads (rVLs). Results: In 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. Limitation: Limited data on case comorbidities and few samples in some cohorts. Conclusion: High, 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 Source: Natural Sciences and Engineering Research Council.

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Section: Discussionsupporting

confidence: 91%

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

Chen

Bobrovitz

Premji

et al. 2021

Preprint

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“…Our group previously profiled cases with non-respiratory symptoms and asymptomatic SARS-CoV-2 infections in Mexico City; we identified that no single symptom offered a reliable assessment of disease severity at the time of initial evaluation, even in population at high risk of contagion such as healthcare workers, as has been confirmed by a recent meta-analysis 23–25 . Given recent evidence which highlights the potential of pre-symptomatic and asymptomatic SARS-CoV-2 transmission and the usefulness of contact tracing as a complement to social distancing and community mitigation policies, SARS-CoV-2 testing should be extended to cases with recent contact with known COVID-19 cases despite the absence of symptoms 22,26,27 . Unfortunately, POCTs have relevant limitations on its diagnostic performance which may question its widespread use to inform public policy or for clinical decision making.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic performance and clinical implications of rapid SARS-CoV-2 antigen testing in Mexico using real-world nationwide COVID-19 registry data

Bello‐Chavolla

Antonio-Villa

Fernández‐Chirino

et al. 2021

Preprint

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BACKGROUNDSARS-CoV-2 testing capacity is important to monitor epidemic dynamics. Given difficulties of large-scale RT-PCR implementation, rapid antigen tests (Rapid Ag-T) have been proposed as alternatives in settings such as Mexico.OBJECTIVESTo evaluate diagnostic performance of Rapid Ag-T for SARS-CoV-2 infection and its associated clinical implications compared to RT-PCR testing in Mexico.METHODSWe analyzed data from the COVID-19 registry of the Mexican General Directorate of Epidemiology up to December 31st, 2020 (n=3,374,165) and cases with both RT-PCR and Rapid Ag-T (n=18,446). We evaluated diagnostic performance using accuracy measures and assessed time-dependent changes in AUROC. We also explored test discordances as predictors of hospitalization, intubation, severe COVID-19 and mortality.RESULTSRapid Ag-T is primarily used in Mexico City. Rapid Ag-T have low sensitivity 37.6% (95%CI 36.6-38.7), high specificity 95.4% (95%CI 95.1-95.8) and acceptable positive 86.1% (95%CI 85.0-86.6) and negative predictive values 67.2% (95%CI 66.2-69.2). Rapid Ag-T has optimal diagnostic performance up to days 7-10 after symptom, and its performance is modified by testing location, comorbidity, and age. RT-PCR(-) / Rapid Ag-T(+) cases had higher risk of adverse COVID-19 outcomes and were older, RT-PCR(+)/ Rapid Ag-T(-) cases had slightly higher risk or adverse outcomes and ≥7 days from symptom onset. Cases detected with rapid Ag-T were younger, without comorbidities, and milder COVID-19 course.CONCLUSIONSRapid Ag-T could be used as an alternative to RT-PCR for large scale SARS-CoV-2 testing in Mexico. Interpretation of Rapid Ag-T results should be done with caution to minimize the risk associated with false negative results.

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“…Early case detection followed by rapid isolation of index cases, alongside contact tracing and quarantine, are therefore key interventions to interrupt onward transmission. As a proportion of individuals with SARS-CoV-2 shed virus while asymptomatic or pauci-symptomatic (2, 3) , there is also global interest in screening tests for at-risk individuals who do not fulfil case definition criteria and in mass testing for early case detection among the general population (4) .…”

Section: Introductionmentioning

confidence: 99%

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection

Rosenheim

Bell

et al. 2021

Preprint

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We hypothesised that host-response biomarkers of viral infections may contribute to early identification of SARS-CoV-2 infected individuals, critical to breaking chains of transmission. We identified 20 candidate blood transcriptomic signatures of viral infection by systematic review and evaluated their ability to detect SARS-CoV-2 infection, compared to the gold-standard of virus PCR tests, among a prospective cohort of 400 hospital staff subjected to weekly testing when fit to attend work. The transcriptional signatures had limited overlap, but were mostly co-correlated as components of type 1 interferon responses. We reconstructed each signature score in blood RNA sequencing data from 41 individuals over sequential weeks spanning a first positive SARS-CoV-2 PCR, and after 6-month convalescence. A single blood transcript for IFI27 provided the highest accuracy for discriminating individuals at the time of their first positive viral PCR result from uninfected controls, with area under the receiver operating characteristic curve (AUROC) of 0.95 (95% confidence interval 0.91–0.99), sensitivity 0.84 (0.7–0.93) and specificity 0.95 (0.85–0.98) at a predefined test threshold. The test performed equally well in individuals with and without symptoms, correlated with viral load, and identified incident infections one week before the first positive viral PCR with sensitivity 0.4 (0.17–0.69) and specificity 0.95 (0.85–0.98). Our findings strongly support further urgent evaluation and development of blood IFI27 transcripts as a biomarker for early phase SARS-CoV-2 infection, for screening individuals such as contacts of index cases, in order to facilitate early case isolation and early antiviral treatments as they emerge.

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Infectivity of asymptomatic versus symptomatic COVID-19

Cited by 174 publications

References 5 publications

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

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

Diagnostic performance and clinical implications of rapid SARS-CoV-2 antigen testing in Mexico using real-world nationwide COVID-19 registry data

Blood transcriptional biomarkers of acute viral infection for detection of pre-symptomatic SARS-CoV-2 infection

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