Using early detection data to estimate the date of emergence of an epidemic outbreak.

While the first infection of an emerging disease is often unknown, information on early cases can be used to date it. In the context of the COVID-19 pandemic, previous studies have estimated dates of emergence (e.g., first human SARS-CoV-2 infection, emergence of the Alpha SARS-CoV-2 variant) using mainly genomic data. Another dating attempt used a stochastic population dynamics approach and the date of the first reported case. Here, we extend this approach to use a larger set of early reported cases to estimate the delay from first infection to the Nth case. We first validate our framework by running our model on simulated data. We then apply our model using data on Alpha variant infections in the UK, dating the first Alpha infection at (median) August 21, 2020 (95% interpercentile range across retained simulations (IPR): July 23-September 5, 2020). Next, we apply our model to data on COVID-19 cases with symptom onset before mid-January 2020. We date the first SARS-CoV-2 infection in Wuhan at (median) November 28, 2019 (95% IPR: November 2-December 9, 2019). Our results fall within ranges previously estimated by studies relying on genomic data. Our population dynamics-based modelling framework is generic and flexible, and thus can be applied to estimate the starting time of outbreaks in contexts other than COVID-19.

Sick leave due to COVID-19 during the first pandemic wave in France, 2020.

OBJECTIVES: To quantify the burden of COVID-19-related sick leave during the first pandemic wave in France, accounting for sick leaves due to symptomatic COVID-19 ('symptomatic sick leaves') and those due to close contact with COVID-19 cases ('contact sick leaves'). METHODS: We combined data from a national demographic database, an occupational health survey, a social behaviour survey and a dynamic SARS-CoV-2 transmission model. Sick leave incidence from 1 March 2020 to 31 May 2020 was estimated by summing daily probabilities of symptomatic and contact sick leaves, stratified by age and administrative region. RESULTS: There were an estimated 1.70M COVID-19-related sick leaves among France's 40M working-age adults during the first pandemic wave, including 0.42M due to COVID-19 symptoms and 1.28M due to COVID-19 contacts. There was great geographical variation, with peak daily sick leave incidence ranging from 230 in Corse (Corsica) to 33 000 in Île-de-France (the greater Paris region), and greatest overall burden in regions of north-eastern France. Regional sick leave burden was generally proportional to local COVID-19 prevalence, but age-adjusted employment rates and contact behaviours also contributed. For instance, 37% of symptomatic infections occurred in Île-de-France, but 45% of sick leaves. Middle-aged workers bore disproportionately high sick leave burden, owing predominantly to greater incidence of contact sick leaves. CONCLUSIONS: France was heavily impacted by sick leave during the first pandemic wave, with COVID-19 contacts accounting for approximately three-quarters of COVID-19-related sick leaves. In the absence of representative sick leave registry data, local demography, employment patterns, epidemiological trends and contact behaviours can be synthesised to quantify sick leave burden and, in turn, predict economic consequences of infectious disease epidemics.

Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example.

In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. Using a mathematical model accounting for the false-negative rates of RT-PCR tests, we computed the incidence rate of SARS-CoV-2 infection among HCWs, while unveiling the proportion of infections remaining undiagnosed despite routine testing. We relied on longitudinal data, including results of routine RT-PCR tests, collected within three Egyptian quarantine hospitals. We estimated an incidence rate (per 100 person-day, PD) of 1.05 (95% CrI 0.58-1.65) at Hospital 1, 1.92 (95% CrI 0.93-3.28) at Hospital 2 and 7.62 (95% CrI 3.47-13.70) at Hospital 3. We found that the risk for an HCW to be infected during a working shift lay within the range of risk levels previously documented in standard healthcare settings for Hospitals 1-2, whereas it was > threefold higher for Hospital 3. This large variation suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.

Can HIV epidemics among MSM be eliminated through participation in preexposure prophylaxis rollouts?

OBJECTIVE: To study the conditions under which preexposure prophylaxis (PrEP) coverage can eliminate HIV among MSM in the Paris region. DESIGN: Mathematical modeling. METHODS: We propose an innovative approach, combining a transmission model with a game-theoretic model, for decision-making about PrEP use. Individuals at high risk of HIV infection decide to use PrEP, depending on their perceived risk of infection and the relative cost of using PrEP versus antiretroviral treatment (ART), which includes monetary and/or nonmonetary aspects, such as price and access model of PrEP, consequences of being infected and lifelong ART. RESULTS: If individuals assessed correctly their infection risk, and the cost of using PrEP were sufficiently low, then the PrEP rollout could lead to elimination. Specifically, assuming 86% PrEP effectiveness, as observed in two clinical trials, a minimum PrEP coverage of 55% [95% confidence interval (CI) 43-64%] among high-risk MSM would achieve elimination in the Paris region. A complete condom drop by MSM using PrEP slightly increases the minimum PrEP coverage required for elimination, by ∼1%, whereas underestimation of their own HIV infection risk would require PrEP programs reduce the cost of using PrEP by a factor ∼2 to achieve elimination. CONCLUSION: Elimination conditions are not yet met in the Paris region, where at most 47% of high-risk MSM were using PrEP as of mid-2019. Further lowering the cost of PrEP and promoting a fair perception of HIV risk are required and should be maintained in the long-run, to maintain elimination status.

Prevention of treatable infectious diseases: A game-theoretic approach.

We model outcomes of voluntary prevention using an imperfect vaccine, which confers protection only to a fraction of vaccinees for a limited duration. Our mathematical model combines a single-player game for the individual-level decision to get vaccinated, and a compartmental model for the epidemic dynamics. Mathematical analysis yields a characterization for the effective vaccination coverage, as a function of the relative cost of prevention versus treatment; note that cost may involve monetary as well as non-monetary aspects. Three behaviors are possible. First, the relative cost may be too high, so individuals do not get vaccinated. Second, the relative cost may be moderate, such that some individuals get vaccinated and voluntary vaccination alleviates the epidemic. In this case, the vaccination coverage grows steadily with decreasing relative cost of vaccination versus treatment. Unlike previous studies, we find a third case where relative cost is sufficiently low so epidemics may be averted through the use of prevention, even for an imperfect vaccine. However, we also found that disease elimination is only temporary-as no equilibrium exists for the individual strategy in this third case-and, with increasing perceived cost of vaccination versus treatment, the situation may be reversed toward the epidemic edge, where the effective reproductive number is 1. Thus, maintaining relative cost sufficiently low will be the main challenge to maintain disease elimination. Furthermore, our model offers insight on vaccine parameters, which are otherwise difficult to estimate. We apply our findings to the epidemiology of measles.