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1.
Topics in Antiviral Medicine ; 30(1 SUPPL):66-67, 2022.
Article in English | EMBASE | ID: covidwho-1880427

ABSTRACT

Background: Transmission of SARS-CoV-2 is highly heterogeneous, with a small fraction of infected individuals (often referred to as "superspreaders") contributing a disproportionate share of forward transmission. Numerous behavioral and environmental explanations have been offered to explain transmission heterogeneity, but the extent to which the underlying features of the infection process within individual hosts contribute towards the superspreading phenomenon remains unclear. In addition, it is not clear how vaccination would impact on the viral infection dynamics and thus the infectiousness of individuals. Addressing these gaps in knowledge will inform the design of more targeted and effective strategies for controlling community spread. Methods: In a study on UIUC campus (UIUC SHIELD), the dynamics of infectious virus and viral RNA shedding were captured through daily longitudinal sampling of 72 individuals for up to 14 days (60 unvaccinated and 12 vaccinated). We fitted mechanistic models to both viral loads and cell culture positivity data, and directly estimated viral reproduction and clearance rates, and overall infectiousness for each individual. Results: Integrating mathematical models with viral load and cell culture positivity data, we show a substantial level of heterogeneity in infectiousness of individual. In unvaccinated individuals, peak viral loads and clearance kinetics of B.1.1.7 and non-variant of concern viruses were indistinguishable. In vaccinated individuals, the viral dynamics do not follow typical patterns of acute infection dynamics and we estimate that these individuals are much less infectious than unvaccinated individuals. Conclusion: Our work provides a high-resolution portrait of SARS-CoV-2 infection dynamics. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Vaccinated individuals are less infectious than unvaccinated individuals overall.

2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334681

ABSTRACT

The dynamics of SARS-CoV-2 replication and shedding in humans remain poorly understood. We captured the dynamics of infectious virus and viral RNA shedding during acute infection through daily longitudinal sampling of 60 individuals for up to 14 days. By fitting mechanistic models, we directly estimate viral reproduction and clearance rates, and overall infectiousness for each individual. Significant person-to-person variation in infectious virus shedding suggests that individual-level heterogeneity in viral dynamics contributes to superspreading. Viral genome load often peaked days earlier in saliva than in nasal swabs, indicating strong compartmentalization and suggesting that saliva may serve as a superior sampling site for early detection of infection. Viral loads and clearance kinetics of B.1.1.7 and non-B.1.1.7 viruses in nasal swabs were indistinguishable, however B.1.1.7 exhibited a significantly slower pre-peak growth rate in saliva. These results provide a high-resolution portrait of SARS-CoV-2 infection dynamics and implicate individual-level heterogeneity in infectiousness in superspreading.

3.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334671

ABSTRACT

The within-host viral kinetics of SARS-CoV-2 infection and how they relate to a person's infectiousness are not well understood. This limits our ability to quantify the impact of interventions on viral transmission. Here, we develop data-driven viral dynamic models of SARS-CoV-2 infection and estimate key within-host parameters such as the infected cell half-life and the within-host reproductive number. We then develop a model linking VL to infectiousness, showing that a person's infectiousness increases sub-linearly with VL. We show that the logarithm of the VL in the upper respiratory tract (URT) is a better surrogate of infectiousness than the VL itself. Using data on VL and the predicted infectiousness, we further incorporated data on antigen and reverse transcription polymerase chain reaction (RT-PCR) tests and compared their usefulness in detecting infection and preventing transmission. We found that RT-PCR tests perform better than antigen tests assuming equal testing frequency;however, more frequent antigen testing may perform equally well with RT-PCR tests at a lower cost, but with many more false-negative tests. Overall, our models provide a quantitative framework for inferring the impact of therapeutics and vaccines that lower VL on the infectiousness of individuals and for evaluating rapid testing strategies. SIGNIFICANCE: Quantifying the kinetics of SARS-CoV-2 infection and individual infectiousness is key to quantitatively understanding SARS-CoV-2 transmission and evaluating intervention strategies. Here we developed data-driven within-host models of SARS-CoV-2 infection and by fitting them to clinical data we estimated key within-host viral dynamic parameters. We also developed a mechanistic model for viral transmission and show that the logarithm of the viral load in the upper respiratory tract serves an appropriate surrogate for a person's infectiousness. Using data on how viral load changes during infection, we further evaluated the effectiveness of PCR and antigen-based testing strategies for averting transmission and identifying infected individuals.

4.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333755

ABSTRACT

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Diagnostic tests and sample types for SARS-CoV-2 vary in sensitivity across the infection period. WHAT IS ADDED BY THIS REPORT?: We show that both RTqPCR (from nasal swab and saliva) and the Quidel SARS Sofia FIA rapid antigen tests peak in sensitivity during the period in which live virus can be detected in nasal swabs, but that the sensitivity of RTqPCR tests rises more rapidly in the pre-infectious period. We also use empirical data to estimate the sensitivities of RTqPCR and antigen tests as a function of testing frequency. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: RTqPCR tests will be more effective than rapid antigen tests at identifying infected individuals prior to or early during the infectious period and thus for minimizing forward transmission (provided results reporting is timely). All modalities, including rapid antigen tests, showed >94% sensitivity to detect infection if used at least twice per week. Regular surveillance/screening using rapid antigen tests 2-3 times per week can be an effective strategy to achieve high sensitivity (>95%) for identifying infected individuals.

5.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-333711

ABSTRACT

BACKGROUND: In early 2020, Ecuador reported one of the highest surges of per capita deaths across the globe. METHODS: We collected a comprehensive dataset containing individual death records between 2015 and 2020 from the Ecuadorian National Institute of Statistics and Census and the Ecuadorian Ministry of Government. We computed the number of excess deaths across time, geographical locations and demographic groups using Poisson regression methods. RESULTS: Between January 1 st and September 23 rd , 2020, the number of excess deaths in Ecuador is 36,402 (95% CI: 35,762-36,827) or 208 per 10 5 population, which is 171% of the expected deaths in that period in a typical year. Only 20% of the excess deaths are attributable to confirmed COVID-19 deaths. Strikingly, in provinces that were most affected by COVID-19, such as Guayas and Santa Elena, the all-cause deaths are more than double the expected number of deaths that would have occurred in a normal year. The extent of excess deaths in men is higher than in women, and the number of excess deaths increases with age. Indigenous populations had the highest level of excess deaths among all ethnic groups. CONCLUSIONS: Overall, the exceptionally high level of excess deaths in Ecuador highlights the enormous burden and heterogeneous impact of COVID-19 on mortality especially in older age groups and indigenous populations in Ecuador that was not fully revealed by COVID-19 death counts. Together with the limited testing in Ecuador, our results suggest that the majority of the excess deaths were likely to be undocumented COVID-19 deaths.

6.
MEDLINE;
Preprint in English | MEDLINE | ID: ppcovidwho-326686

ABSTRACT

Resistance mutations to monoclonal antibody (mAb) therapy has been reported, but in the non-immunosuppressed population, it is unclear if in vivo emergence of SARS-CoV-2 resistance mutations alters either viral replication dynamics or therapeutic efficacy. In ACTIV-2/A5401, non-hospitalized participants with symptomatic SARS-CoV-2 infection were randomized to bamlanivimab (700mg or 7000mg) or placebo. Treatment-emergent resistance mutations were significantly more likely detected after bamlanivimab 700mg treatment than placebo (7% of 111 vs 0% of 112 participants, P=0.003). There were no treatment-emergent resistance mutations among the 48 participants who received bamlanivimab 7000mg. Participants with emerging mAb resistant virus had significantly higher pre-treatment nasopharyngeal and anterior nasal viral load. Intensive respiratory tract viral sampling revealed the dynamic nature of SARS-CoV-2 evolution, with evidence of rapid and sustained viral rebound after emergence of resistance mutations, and worsened symptom severity. Participants with emerging bamlanivimab resistance often accumulated additional polymorphisms found in current variants of concern/interest and associated with immune escape. These results highlight the potential for rapid emergence of resistance during mAb monotherapy treatment, resulting in prolonged high level respiratory tract viral loads and clinical worsening. Careful virologic assessment should be prioritized during the development and clinical implementation of antiviral treatments for COVID-19.

7.
Topics in Antiviral Medicine ; 29(1):34, 2021.
Article in English | EMBASE | ID: covidwho-1250344

ABSTRACT

Background: The within-host reproductive number R0 is an important parameter to predict the minimum antiviral efficacy needed to suppress viral infection. However, this parameter has not been well quantified for SARS-CoV-2. This is because accurate estimation of this quantity requires longitudinal viral load measurements during the initial phase of infection, when the virus population expands before the viral load peak;yet, most available measurements are made after the viral load peak. Methods: We constructed viral dynamic models to describe a set of longitudinal viral load data from a study where individuals were tested frequently such that viral loads during the viral expansion phase were measured. We fit multiple models to data from a total of 42 infected individuals (14 symptomatic and 28 asymptomatic) to estimate R0 and used a model linking within-host viral load to the infectiousness of a person to evaluate the infectiousness of asymptomatic individuals compared to symptomatic individuals. Results: We estimated that the within-host R0 is between 8-16 across the 48 individuals. This suggests that antiviral efficacy has to be greater than 95% to suppress virus infection in a majority of individuals. The estimated R0 in asymptomatic individuals is lower than in symptomatic individuals (mean 10.0 vs. 13.8;p-value<0.0001). Our model suggests there exists large heterogeneity in infectiousness among individuals, and asymptomatic individuals may be on average 15% less infectious than symptomatic individuals (p-value=0.02), not considering isolation measures. Conclusion: An antiviral efficacy of 95% or more is needed to suppress viral infection in most infected individuals. Asymptomatic individuals may be slightly less infectious than symptomatic individuals.

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