In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Ke, Ruian; Zitzmann, Carolin; Ho, David D.; Ribeiro, Ruy M.; Perelson, Alan S.

doi:10.1073/pnas.2111477118

Cited by 137 publications

(268 citation statements)

References 57 publications

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“…We assumed that the two quantities can be described by a density dependent function ( Eq. 7 in Materials and Methods ) as in [8, 13]. Through fitting this function to the population ( R u , V u ) data in the three groups (taking into consideration the presence of censored data, see Materials and Methods for full explanation), we found that the level of infectious viruses increases sub-linearly with increases in viral RNA, with the same exponent h=0.6 in all three groups.…”

Section: Resultsmentioning

confidence: 94%

“…Over the last two years, within-host mathematical models developed for influenza and other respiratory infections have been modified for SARS-CoV-2 infections [10, 11, 13, 15, 23, 31]. These models divided total viral titers into infectious and non-infectious particles [7, 27], fitted their sum to total RNA values measured by PCR (used as a proxy for total virus load) and used the results to determine the mechanisms of viral expansion and loss.…”

Section: Introductionmentioning

confidence: 99%

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Modeling within-host and aerosol dynamics of SARS-CoV-2: the relationship with infectiousness

Heitzman-Breen

Ciupe

2022

Preprint

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The relationship between transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the amount of virus present in the proximity of a susceptible host is not understood. Here, we developed a within-host and aerosol mathematical model and used it to determine the relationship between viral kinetics in the upper respiratory track, viral kinetics in the aerosols, and new transmissions in golden hamsters challenged with SARS-CoV-2. We determined that infectious virus shedding early in infection correlates with transmission events, shedding of infectious virus diminishes late in the infection, and high viral RNA levels late in the infection is a poor indicator of transmission. We further showed that viral infectiousness increases in a density dependent manner with viral RNA and that their relative ratio is time-dependent. Such information is useful for designing interventions.Author summaryQuantifying the relationship between SARS-CoV-2 dynamics in upper respiratory tract and in aerosols is key to understanding SARS-CoV-2 transmission and evaluating intervention strategies. Of particular interest is the link between the viral RNA measured by PCR and a subject’s infectiousness. Here, we developed a mechanistic model of viral transmission in golden hamsters and used data in upper respiratory tract and aerosols to evaluate key within-host and environment based viral parameters. The significance of our research is in identifying the timing and duration of viral shedding, how long it stays infectious, and the link between infectious virus and total viral RNA. Such knowledge enhances our understanding of the SARS-CoV-2 transmission window.

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Section: Resultsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Modeling within-host and aerosol dynamics of SARS-CoV-2: the relationship with infectiousness

Heitzman-Breen

Ciupe

2022

Preprint

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“…Finally, second precursor cells differentiate into effector cells at the same per capita rate q and are cleared at rate δ E . Other models have described withinhost viral loads differently, including by using multiple compartments and without an adaptive immune response [51][52][53].…”

Section: Data-validated Sars-cov-2 Within-host Model Captures Viral L...mentioning

confidence: 99%

Multi-scale modelling reveals that early super-spreader events are a likely contributor to novel variant predominance

Goyal

Reeves

Schiffer

2022

J. R. Soc. Interface.

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The emergence of new SARS-CoV-2 variants of concern (VOC) has hampered international efforts to contain the COVID-19 pandemic. VOCs have been characterized to varying degrees by higher transmissibility, worse infection outcomes and evasion of vaccine and infection-induced immunologic memory. VOCs are hypothesized to have originated from animal reservoirs, communities in regions with low surveillance and/or single individuals with poor immunologic control of the virus. Yet, the factors dictating which variants ultimately predominate remain incompletely characterized. Here we present a multi-scale model of SARS-CoV-2 dynamics that describes population spread through individuals whose viral loads and numbers of contacts (drawn from an over-dispersed distribution) are both time-varying. This framework allows us to explore how super-spreader events (SSE) (defined as greater than five secondary infections per day) contribute to variant emergence. We find stochasticity remains a powerful determinant of predominance. Variants that predominate are more likely to be associated with higher infectiousness, an SSE early after variant emergence and ongoing decline of the current dominant variant. Additionally, our simulations reveal that most new highly infectious variants that infect one or a few individuals do not achieve permanence in the population. Consequently, interventions that reduce super-spreading may delay or mitigate emergence of VOCs.

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“…We chose not to fit mechanistic models (e.g. [15]) as the goal was not explain the biology underlying viral clearance but to provide a robust method from which to infer summary statistics for virological clinical trial endpoints.…”

Section: Model Of Viral Clearance Dynamicsmentioning

confidence: 99%

Characterising SARS-CoV-2 viral clearance kinetics to improve the design of antiviral pharmacometric studies

Watson

Kissler

Npj.

et al. 2021

Preprint

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There is no agreed methodology for pharmacometric assessment of candidate antiviral drugs in COVID-19. The most widely used measure of virological response in clinical trials so far is the time to viral clearance assessed by qPCR of viral nucleic acid in eluates from serial nasopharyngeal swabs. We posited that the rate of viral clearance would have better discriminatory value. Using a pharmacodynamic model fit to individual SARS-CoV-2 virus clearance data from 46 uncomplicated COVID-19 infections in a cohort of prospectively followed adults, we simulated qPCR viral load data to compare type 2 errors when using time to clearance and rate of clearance under varying antiviral effects, sample sizes, sampling frequencies and durations of follow-up. The rate of viral clearance is a uniformly superior endpoint as compared to time to clearance with respect to type 2 error, and it is not dependent on initial viral load or assay sensitivity. For greatest efficiency pharmacometric assessments should be conducted in early illness and daily qPCR samples should be taken over 7 to 10 days in each patient studied. Adaptive randomisation and early stopping for success permits more rapid identification of active interventions.

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In vivo kinetics of SARS-CoV-2 infection and its relationship with a person’s infectiousness

Cited by 137 publications

References 57 publications

Modeling within-host and aerosol dynamics of SARS-CoV-2: the relationship with infectiousness

Modeling within-host and aerosol dynamics of SARS-CoV-2: the relationship with infectiousness

Multi-scale modelling reveals that early super-spreader events are a likely contributor to novel variant predominance

Characterising SARS-CoV-2 viral clearance kinetics to improve the design of antiviral pharmacometric studies

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