High infectiousness immediately before COVID-19 symptom onset highlights the importance of continued contact tracing

Hart, William S; Maini, Philip K.; Thompson, Robin N

doi:10.7554/elife.65534

Cited by 70 publications

(86 citation statements)

References 49 publications

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“…Compared to the ODE model, SIMCoV produced a less pronounced peak with higher viral loads early in infection that persisted for several days. The SIMCoV curves are consistent with the observation that individuals infected with SARS-CoV-2 are most infectious early in infection before symptom onset [39,40]. The SIMCoV runs also predict that elevated viral titers persist for more days, which agrees with patient viral load data.…”

Section: Plos Computational Biologysupporting

confidence: 81%

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection

et al. 2021

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A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads. The model also shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. By incorporating spatial interactions, SIMCoV provides a parsimonious explanation for the dramatically different viral load trajectories among patients by varying only the number of initial sites of infection and the magnitude and timing of the T cell immune response. When the branching airway structure of the lung is explicitly represented, we find that virus spreads faster than in a 2D layer of epithelial cells, but much more slowly than in an undifferentiated 3D grid or in a well-mixed differential equation model. These results illustrate how realistic, spatially explicit computational models can improve understanding of within-host dynamics of SARS-CoV-2 infection.

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Section: Plos Computational Biologysupporting

confidence: 81%

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection

et al. 2021

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“…It is clear that more research is needed on this topic to correlate viral load with symptoms and clinical outcomes (Mahallawi et al, 2021). Hart et al (2021) showed that about 65% of virus transmission occurs before symptoms develop. Thus, individuals circulate in the general community before their infections are detected (Hart et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“… Hart et al (2021) showed that about 65% of virus transmission occurs before symptoms develop. Thus, individuals circulate in the general community before their infections are detected ( Hart et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Saliva Quantification of SARS-CoV-2 in Real-Time PCR From Asymptomatic or Mild COVID-19 Adults

et al. 2022

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The fast spread of COVID-19 is related to the highly infectious nature of SARS-CoV-2. The disease is suggested to be transmitted through saliva droplets and nasal discharge. The saliva quantification of SARS-CoV-2 in real-time PCR from asymptomatic or mild COVID-19 adults has not been fully documented. This study analyzed the relationship between salivary viral load on demographics and clinical characteristics including symptoms, co-morbidities in 160 adults diagnosed as COVID-19 positive patients recruited between September and December 2020 in four French centers. Median initial viral load was 4.12 log10 copies/mL (IQR 2.95–5.16; range 0–10.19 log10 copies/mL). 68.6% of adults had no viral load detected. A median load reduction of 23% was observed between 0–2 days and 3–5 days, and of 11% between 3–5 days and 6–9 days for the delay from onset of symptoms to saliva sampling. No significant median difference between no-symptoms vs. symptoms patients was observed. Charge was consistently similar for the majority of the clinical symptoms excepted for headache with a median load value of 3.78 log10 copies/mL [1.95–4.58] (P < 0.003). SARS-CoV-2 RNA viral load was associated with headache and gastro-intestinal symptoms. The study found no statistically significant difference in viral loads between age groups, sex, or presence de co-morbidity. Our data suggest that oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

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“…Isolation of nonsymptomatic hosts was more effective at reducing the local outbreak probability than isolation of symptomatic hosts ( Figs 6 A,B), although of course this is more challenging to achieve ( Lovell-Read et al, 2021 ). However, if fast isolation of nonsymptomatic hosts could be achieved through efficient large-scale testing (potentially in combination with contact tracing ( Hart et al, 2021 ), the probability of local outbreaks could be reduced substantially through this measure alone.…”

Section: Resultsmentioning

confidence: 99%

Estimating local outbreak risks and the effects of non-pharmaceutical interventions in age-structured populations: SARS-CoV-2 as a case study

Lovell-Read

Shen

Thompson

2022

Journal of Theoretical Biology

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During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) including school closures, workplace closures and social distancing policies have been employed worldwide to reduce transmission and prevent local outbreaks. However, transmission and the effectiveness of NPIs depend strongly on age-related factors including heterogeneities in contact patterns and pathophysiology. Here, using SARS-CoV-2 as a case study, we develop a branching process model for assessing the risk that an infectious case arriving in a new location will initiate a local outbreak, accounting for the age distribution of the host population. We show that the risk of a local outbreak depends on the age of the index case, and we explore the effects of NPIs targeting individuals of different ages. Social distancing policies that reduce contacts outside of schools and workplaces and target individuals of all ages are predicted to reduce local outbreak risks substantially, whereas school closures have a more limited impact. In the scenarios considered here, when different NPIs are used in combination the risk of local outbreaks can be eliminated. We also show that heightened surveillance of infectious individuals reduces the level of NPIs required to prevent local outbreaks, particularly if enhanced surveillance of symptomatic cases is combined with efforts to find and isolate nonsymptomatic infected individuals. Our results reflect real-world experience of the COVID-19 pandemic, during which combinations of intense NPIs have reduced transmission and the risk of local outbreaks. The general modelling framework that we present can be used to estimate local outbreak risks during future epidemics of a range of pathogens, accounting fully for age-related factors.

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High infectiousness immediately before COVID-19 symptom onset highlights the importance of continued contact tracing

Cited by 70 publications

References 49 publications

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection

Spatially distributed infection increases viral load in a computational model of SARS-CoV-2 lung infection

Saliva Quantification of SARS-CoV-2 in Real-Time PCR From Asymptomatic or Mild COVID-19 Adults

Estimating local outbreak risks and the effects of non-pharmaceutical interventions in age-structured populations: SARS-CoV-2 as a case study

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