The COVID‐19 pandemic has led to a resurgence of the debate on whether host–parasite interactions should evolve towards avirulence. In this review, we first show that SARS‐CoV‐2 virulence is ...evolving, before explaining why some expect the mortality caused by the epidemic to converge towards that of human seasonal alphacoronaviruses. Leaning on existing theory, we then include viral evolution into the picture and discuss hypotheses explaining why the virulence has increased since the beginning of the pandemic. Finally, we mention some potential scenarios for the future.
Why has SARS‐CoV‐2 virulence increased since 2020? Has it reached an evolutionary dead end or will it become a harmless virus? In this review, we particulary highlight three potential scenarios for the future evolution of SARS‐CoV‐2: i) towards avirulence (if tranmission and virulence are independent), ii) towards a higher virulence that optimises its trade‐off with transmission (fully adaptive path), or iii) towards an intermediate virulence level following a path difficult to anticipate, shaped by the yet poorly known adaptive landscape (maladaptive virulence evolution).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In an epidemic, individuals can widely differ in the way they spread the infection depending on their age or on the number of days they have been infected for. In the absence of pharmaceutical ...interventions such as a vaccine or treatment, non-pharmaceutical interventions (e.g. physical or social distancing) are essential to mitigate the pandemic. We develop an original approach to identify the optimal age-stratified control strategy to implement as a function of the time since the onset of the epidemic. This is based on a model with a double continuous structure in terms of host age and time since infection. By applying optimal control theory to this model, we identify a solution that minimizes deaths and costs associated with the implementation of the control strategy itself. We also implement this strategy for three countries with contrasted age distributions (Burkina-Faso, France, and Vietnam). Overall, the optimal strategy varies throughout the epidemic, with a more intense control early on, and depending on host age, with a stronger control for the older population, except in the scenario where the cost associated with the control is low. In the latter scenario, we find strong differences across countries because the control extends to the younger population for France and Vietnam 2 to 3 months after the onset of the epidemic, but not for Burkina Faso. Finally, we show that the optimal control strategy strongly outperforms a constant uniform control exerted over the whole population or over its younger fraction. This improved understanding of the effect of age-based control interventions opens new perspectives for the field, especially for age-based contact tracing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Projects such as the European Covid-19 Forecast Hub publish forecasts on the national level for new deaths, new cases, and hospital admissions, but not direct measurements of hospital strain like ...critical care bed occupancy at the sub-national level, which is of particular interest to health professionals for planning purposes. We present a sub-national French framework for forecasting hospital strain based on a non-Markovian compartmental model, its associated online visualisation tool and a retrospective evaluation of the real-time forecasts it provided from January to December 2021 by comparing to three baselines derived from standard statistical forecasting methods (a naive model, auto-regression, and an ensemble of exponential smoothing and ARIMA). In terms of median absolute error for forecasting critical care unit occupancy at the two-week horizon, our model only outperformed the naive baseline for 4 out of 14 geographical units and underperformed compared to the ensemble baseline for 5 of them at the 90% confidence level (n = 38). However, for the same level at the 4 week horizon, our model was never statistically outperformed for any unit despite outperforming the baselines 10 times spanning 7 out of 14 geographical units. This implies modest forecasting utility for longer horizons which may justify the application of non-Markovian compartmental models in the context of hospital-strain surveillance for future pandemics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
4.
SARS-CoV-2 viral RNA levels are not 'viral load' Michalakis, Yannis; Sofonea, Mircea T.; Alizon, Samuel ...
Trends in microbiology (Regular ed.),
11/2021, Volume:
29, Issue:
11
Journal Article
Peer reviewed
Open access
Ct values are commonly used as proxies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 'viral load'. Since coronaviruses are positive single-stranded RNA (+)ssRNA viruses, current ...reverse transcription (RT)-qPCR target amplification does not distinguish replicative from transcriptional RNA. Although analyses of Ct values remain informative, equating them with viral load may lead to flawed conclusions as it is presently unknown whether (and to what extent) variation in Ct reflects variation in viral load or in gene expression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We analyzed 324,734 SARS-CoV-2 variant screening tests from France enriched with 16,973 whole-genome sequences sampled during September 1, 2021-February 28, 2022. Results showed the estimated growth ...advantage of the Omicron variant over the Delta variant to be 105% (95% CI 96%-114%) and that of the BA.2 lineage over the BA.1 lineage to be 49% (95% CI 44%-52%). Quantitative PCR cycle threshold values were consistent with an increased ability of Omicron to generate breakthrough infections. Epidemiologic modeling shows that, in spite of its decreased virulence, the Omicron variant can generate important critical COVID-19 activity in hospitals in France. The magnitude of the BA.2 wave in hospitals depends on the level of relaxing of control measures but remains lower than that of BA.1 in median scenarios.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human Papillomaviruses (HPV) are one of the most prevalent sexually transmitted infections (STI) and the most oncogenic viruses known to humans. The vast majority of HPV infections clear in less than ...3 years, but the underlying mechanisms, especially the involvement of the immune response, are still poorly known. Building on earlier work stressing the importance of randomness in the type of cell divisions in the clearance of HPV infection, we develop a stochastic mathematical model of HPV dynamics that combines the previous aspect with an explicit description of the intracellular level. We show that the random partitioning of virus episomes upon stem cell division and the occurrence of symmetric divisions dramatically affect viral persistence. These results call for more detailed within-host studies to better understand the relative importance of stochasticity and immunity in HPV infection clearance.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Natural populations often have to cope with genetically distinct parasites that can coexist, or not, within the same hosts. Theoretical models addressing the evolution of virulence have considered ...two within host infection outcomes, namely superinfection and coinfection. The field somehow became limited by this dichotomy that does not correspond to an empirical reality as other infection patterns, namely sets of within-host infection outcomes, are possible. We indeed formally prove there are over one hundred different infection patterns solely for recoverable chronic infections caused by two genetically distinct horizontally-transmitted microparasites. We afterwards highlight eight infection patterns using an explicit modelling of within-host dynamics that captures a large range of ecological interactions, five of which have been neglected so far. To clarify the terminology related to multiple infections, we introduce terms describing these new relevant patterns and illustrate them with existing biological systems. These infection patterns constitute a new framework for linking within-host and between-host dynamics, which is a requirement to forward our understanding of the epidemiology and the evolution of parasites.
•There are over a hundred possible distinct patterns of chronic dimorphic infections.•Simple within-host dynamics generate 7 biologically supported infection patterns.•We discuss and clarify the terminology of the multiple infection literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Variants of severe acute respiratory syndrome coronavirus 2 raise concerns regarding the control of coronavirus disease epidemics. We analyzed 40,000 specific reverse transcription PCR tests ...performed on positive samples during January 26-February 16, 2021, in France. We found high transmission advantage of variants and more advanced spread than anticipated.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many hosts are infected by several parasite genotypes at a time. In these co-infected hosts, parasites can interact in various ways thus creating diverse within-host dynamics, making it difficult to ...predict the expression and the evolution of virulence. Moreover, multiple infections generate a combinatorial diversity of cotransmission routes at the host population level, which complicates the epidemiology and may lead to non-trivial outcomes. We introduce a new model for multiple infections, which allows any number of parasite genotypes to infect hosts and potentially coexist in the population. In our model, parasites affect one another's within-host growth through density-dependent interactions and by means of public goods and spite. These within-host interactions determine virulence, recovery and transmission rates, which are then integrated in a transmission network. We use analytical solutions and numerical simulations to investigate epidemiological feedbacks in host populations infected by several parasite genotypes. Finally, we discuss general perspectives on multiple infections.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Simulating nationwide realistic individual movements with a detailed geographical structure can help optimise public health policies. However, existing tools have limited resolution or can only ...account for a limited number of agents. We introduce Epidemap, a new framework that can capture the daily movement of more than 60 million people in a country at a building-level resolution in a realistic and computationally efficient way. By applying it to the case of an infectious disease spreading in France, we uncover hitherto neglected effects, such as the emergence of two distinct peaks in the daily number of cases or the importance of local density in the timing of arrival of the epidemic. Finally, we show that the importance of super-spreading events strongly varies over time.
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