Viral dynamics of acute SARS-CoV-2 infection

Kissler, Stephen M; Fauver, Joseph R.; Mack, Christina; Olesen, Scott W.; Tai, Caroline G.; Shiue, Kristin Y.; Kalinich, Chaney C.; Jednak, Sarah; Ott, Isabel M.; Vogels, Chantal B.F.; Wohlgemuth, Jay; Weisberger, James; DiFiori, John P.; Anderson, Deverick J.; Mancell, Jimmie; Ho, David D.; Grubaugh, Nathan D.; Grad, Yonatan H.

doi:10.1101/2020.10.21.20217042

Cited by 91 publications

(88 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the simplifying assumptions we have made is that the Ct curve is a reasonable proxy for both probability of detection by testing (with both PCR and LFA) and potential for transmission. Alternative parameterisations of transmission potential are possible, 24 but unresolved challenges in comparing testing approaches with the transmission potential based on a combination of an incubation period 9 and infectivity relative to onset of symptoms 25 include the need to convert from PCR sensitivity curves 26 , 27 to LFA in such a way that the timing and height of the two curves are matched meaningfully. A more complete picture of daily testing would require mapping a curve of viral load to one of test sensitivity and one of infectivity.…”

Section: Discussionmentioning

confidence: 99%

“…The timing of the peak Ct was sampled from the incubation period (time from exposure to onset of symptoms) using the pooled log-normal distribution from a published meta-analysis. 10 The peak Ct value is normally distributed with mean 22·3 and SD of 4·2 9 and the time of cessation of viral shedding, a return to baseline, is parameterised as normally distributed with mean 17 days after exposure and SD of 0·94 days for symptomatic individuals, 11 with asymptomatic individuals having a duration that is 40% shorter. 10 The peak and end times are drawn, for each individual, in such a way that each individual is at the same quantile, q, in the cumulative densities of each distribution; this guarantees that the ordering of peak and end is maintained and that there are no rapid returns to baseline Ct after a slow transition to peak Ct. We then fit a cubic Hermite spline 12 to the generated exposure, peak, and end values for each individual, constraining the slope of the curve to be zero at each of them, to simulate viral load kinetics (in Ct) over the course of infection.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study

Quilty

Clifford

Hellewell

et al. 2021

The Lancet Public Health

178

180

View full text Add to dashboard Cite

Background In most countries, contacts of confirmed COVID-19 cases are asked to quarantine for 14 days after exposure to limit asymptomatic onward transmission. While theoretically effective, this policy places a substantial social and economic burden on both the individual and wider society, which might result in low adherence and reduced policy effectiveness. We aimed to assess the merit of testing contacts to avert onward transmission and to replace or reduce the length of quarantine for uninfected contacts. MethodsWe used an agent-based model to simulate the viral load dynamics of exposed contacts, and their potential for onward transmission in different quarantine and testing strategies. We compared the performance of quarantines of differing durations, testing with either PCR or lateral flow antigen (LFA) tests at the end of quarantine, and daily LFA testing without quarantine, against the current 14-day quarantine strategy. We also investigated the effect of contact tracing delays and adherence to both quarantine and self-isolation on the effectiveness of each strategy.Findings Assuming moderate levels of adherence to quarantine and self-isolation, self-isolation on symptom onset alone can prevent 35% (95% uncertainty interval [UI] 10-59) of onward transmission potential from secondary cases. 14 days of post-exposure quarantine reduces transmission by 48% (95% UI 18-79). Quarantine with release after a negative PCR test 7 days after exposure might avert a similar proportion (50%, 95% UI 23-80; risk ratio [RR] 1•02, 95% UI 0•88-1•41) to that of the 14-day quarantine period, as would quarantine with a negative LFA test 7 days after exposure (49%, 95% UI 20-78; RR 1•00, 0•82-1•28) or daily LFA testing without quarantine for 5 days after tracing (50%, 95% UI 24-79; RR 1•04, 0•69-1•79) if all tests are returned negative. A stronger effect might be possible if individuals isolate more strictly after a positive test and if contacts can be notified faster.Interpretation Testing might allow for a substantial reduction in the length of, or replacement of, quarantine in the control of onwards transmission from contacts of SARS-CoV-2-infected individuals. Decreasing test and trace delays and increasing adherence will further increase the effectiveness of these strategies. Further research is required to empirically evaluate the potential costs (increased transmission risk, false reassurance) and benefits (reduction in the burden of quarantine, increased adherence) of such strategies before adoption as policy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study

Quilty

Clifford

Hellewell

et al. 2021

The Lancet Public Health

178

180

View full text Add to dashboard Cite

show abstract

“…Alternatively, it is also possible that a proportion of infected people never shed virus at high enough viral loads to allow efficient transmission. This possibility speaks to the need for more quantitative viral load data gathered during the initial stages of infection ( Kissler, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Viral load and contact heterogeneity predict SARS-CoV-2 transmission and super-spreading events

Goyal

Reeves

Cardozo-Ojeda

et al. 2021

eLife

174

215

View full text Add to dashboard Cite

SARS-CoV-2 is difficult to contain because many transmissions occur during pre-symptomatic infection. Unlike influenza, most SARS-CoV-2 infected people do not transmit while a small percentage infect large numbers of people. We designed mathematical models which link observed viral loads with epidemiologic features of each virus, including distribution of transmissions attributed to each infected person and duration between symptom onset in the transmitter and secondarily infected person. We identify that people infected with SARS-CoV-2 or influenza can be highly contagious for less than one day, congruent with peak viral load. SARS-CoV-2 super-spreader events occur when an infected person is shedding at a very high viral load and has a high number of exposed contacts. The higher predisposition of SARS-CoV-2 towards super-spreading events cannot be attributed to additional weeks of shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks, likely due to aerosolization.

show abstract

“…The copyright holder for this preprint this version posted November 6, 2020. ; https://doi.org/10.1101/2020.11.04.20224758 doi: medRxiv preprint Figure S4). C) Following a three to five day latent period, viral load is modeled to increase rapidly for two to five 9 is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

Section: Table 1 Interventions Summarymentioning

confidence: 99%

Frequent testing and immunity-based staffing will help mitigate outbreaks in nursing home settings

Holmdahl

Kahn

Hay

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Nursing homes and other long term care facilities have been disproportionately impacted by the COVID-19 pandemic. Strategies are urgently needed to reduce transmission in these vulnerable populations. We aimed to evaluate the reduction in transmission in nursing homes achieved through contact-targeted interventions and testing and to evaluate the effectiveness of two types of screening tests conducted with varying frequency: 1) rapid antigen testing and 2) PCR testing. Methods: We developed an agent-based Susceptible-Exposed-Infectious(Asymptomatic/Symptomatic)-Recovered (SEIR) model to examine SARS-CoV-2 transmission in nursing homes. Residents and staff are modelled individually; residents are split into two cohorts based on COVID-19 diagnosis. In the resident cohorting intervention, recovered residents are moved back from the COVID (infected) cohort to the non-COVID (susceptible/uninfected) cohort. In the immunity-based staffing intervention, recovered staff, who we assume have protective immunity, are assigned to work in the non-COVID cohort, while susceptible staff work in the COVID cohort and are assumed to have high levels of protection from personal protective equipment. These interventions aim to reduce the fraction of people's contacts that are presumed susceptible (and therefore potentially infected) and replace them with recovered (immune) contacts. Results: The frequency and type of testing has a larger impact on the size of outbreaks than the cohorting and staffing interventions. The most effective testing strategies modeled are daily antigen testing of everyone and daily antigen testing of staff with weekly PCR testing for residents. Under all screening testing strategies, the immunity-based staffing intervention reduces the final size of the outbreak. The resident cohorting intervention reduces the final outbreak size under some, but not all, testing scenarios. Conclusions: Increasing the frequency of screening testing of all residents and staff, or even staff alone, in nursing homes has the potential to greatly reduce outbreaks in this vulnerable setting. Immunity-based staffing can further reduce spread at little or no additional cost and becomes particularly important when daily testing is not feasible.

show abstract

Viral dynamics of acute SARS-CoV-2 infection

Cited by 91 publications

References 22 publications

Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study

Quarantine and testing strategies in contact tracing for SARS-CoV-2: a modelling study

Viral load and contact heterogeneity predict SARS-CoV-2 transmission and super-spreading events

Frequent testing and immunity-based staffing will help mitigate outbreaks in nursing home settings

Contact Info

Product

Resources

About