Host heterogeneity and epistasis explain punctuated evolution of SARS-CoV-2.

Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines.

Immune Heterogeneity and Epistasis Explain Punctuated Evolution of SARS-CoV-2.

Identifying drivers of viral diversity is key to understanding the evolutionary as well as epidemiological dynamics of the COVID-19 pandemic. Using rich viral genomic data sets, we show that periods of steadily rising diversity have been punctuated by sudden, enormous increases followed by similarly abrupt collapses of diversity. We introduce a mechanistic model of saltational evolution with epistasis and demonstrate that these features parsimoniously account for the observed temporal dynamics of inter-genomic diversity. Our results provide support for recent proposals that saltational evolution may be a signature feature of SARS-CoV-2, allowing the pathogen to more readily evolve highly transmissible variants. These findings lend theoretical support to a heightened awareness of biological contexts where increased diversification may occur. They also underline the power of pathogen genomics and other surveillance streams in clarifying the phylodynamics of emerging and endemic infections. In public health terms, our results further underline the importance of equitable distribution of up-to-date vaccines.

Lockdowns exert selection pressure on overdispersion of SARS-CoV-2 variants.

The SARS-CoV-2 ancestral strain has caused pronounced superspreading events, reflecting a disease characterized by overdispersion, where about 10% of infected people cause 80% of infections. New variants of the disease have different person-to-person variability in viral load, suggesting for example that the Alpha (B.1.1.7) variant is more infectious but relatively less prone to superspreading. Meanwhile, non-pharmaceutical mitigation of the pandemic has focused on limiting social contacts (lockdowns, regulations on gatherings) and decreasing transmission risk through mask wearing and social distancing. Using a mathematical model, we show that the competitive advantage of disease variants may heavily depend on the restrictions imposed. In particular, we find that lockdowns exert an evolutionary pressure which favours variants with lower levels of overdispersion. Our results suggest that overdispersion is an evolutionarily unstable trait, with a tendency for more homogeneously spreading variants to eventually dominate.

Differences in social activity increase efficiency of contact tracing.

ABSTRACT: Digital contact tracing has been suggested as an effective strategy for controlling an epidemic without severely limiting personal mobility. Here, we use smartphone proximity data to explore how social structure affects contact tracing of COVID-19. We model the spread of COVID-19 and find that the effectiveness of contact tracing depends strongly on social network structure and heterogeneous social activity. Contact tracing is shown to be remarkably effective in a workplace environment and the effectiveness depends strongly on the minimum duration of contact required to initiate quarantine. In a realistic social network, we find that forward contact tracing with immediate isolation can reduce an epidemic by more than 70%. In perspective, our findings highlight the necessity of incorporating social heterogeneity into models of mitigation strategies. SUPPLEMENTARY INFORMATION: The online version supplementary material available at 10.1140/epjb/s10051-021-00222-8.

The COVID-19 pandemic: key considerations for the epidemic and its control.

The response to the ongoing COVID-19 pandemic has been characterized by draconian measures and far too many important unknowns, such as the true mortality risk, the role of children as transmitters and the development and duration of immunity in the population. More than a year into the pandemic much has been learned and insights into this novel type of pandemic and options for control are shaping up. Using a historical lens, we review what we know and still do not know about the ongoing COVID-19 pandemic. A pandemic caused by a member of the coronavirus family is a new situation following more than a century of influenza A pandemics. However, recent pandemic threats such as outbreaks of the related and novel deadly coronavirus SARS in 2003 and of MERS since 2012 had put coronaviruses on WHOs blueprint list of priority diseases. Like pandemic influenza, SARS-CoV-2 is highly transmissible (R0 ~ 2.5). Furthermore, it can fly under the radar due to a broad clinical spectrum where asymptomatic and pre-symptomatic infected persons also transmit the virus-including children. COVID-19 is far more deadly than seasonal influenza; initial data from China suggested a case fatality rate of 2.3%-which would have been on par with the deadly 1918 Spanish influenza. But, while the Spanish influenza killed young, otherwise healthy adults, it is the elderly who are at extreme risk of dying of COVID-19. We review available seroepidemiological evidence of infection rates and compute infection fatality rates (IFR) for Denmark (0.5%), Spain (0.85%), and Iceland (0.3%). We also deduce that population age structure is key. SARS-CoV-2 is characterized by superspreading, so that ~10% of infected individuals yield 80% of new infections. This phenomenon turns out to be an Achilles heel of the virus that may explain our ability to effectively mitigate outbreaks so far. How will this pandemic come to an end? Herd immunity has not been achieved in Europe due to intense mitigation by non-pharmaceutical interventions; for example, only ~8% of Danes were infected across the 1st and 2nd wave. Luckily, we now have several safe and effective vaccines. Global vaccine control of the pandemic depends in great measure on our ability to keep up with current and future immune escape variants of the virus. We should thus be prepared for a race between vaccine updates and mutations of the virus. A permanent reopening of society highly depends on winning that race.

COVID-19 Superspreading Suggests Mitigation by Social Network Modulation.

Although COVID-19 has caused severe suffering globally, the efficacy of nonpharmaceutical interventions has been greater than typical models have predicted. Meanwhile, evidence is mounting that the pandemic is characterized by superspreading. Capturing this phenomenon theoretically requires modeling at the scale of individuals. Using a mathematical model, we show that superspreading drastically enhances mitigations which reduce the overall personal contact number and that social clustering increases this effect.

Overdispersion in COVID-19 increases the effectiveness of limiting nonrepetitive contacts for transmission control.

Increasing evidence indicates that superspreading plays a dominant role in COVID-19 transmission. Recent estimates suggest that the dispersion parameter k for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is on the order of 0.1, which corresponds to about 10% of cases being the source of 80% of infections. To investigate how overdispersion might affect the outcome of various mitigation strategies, we developed an agent-based model with a social network that allows transmission through contact in three sectors: "close" (a small, unchanging group of mutual contacts as might be found in a household), "regular" (a larger, unchanging group as might be found in a workplace or school), and "random" (drawn from the entire model population and not repeated regularly). We assigned individual infectivity from a gamma distribution with dispersion parameter k We found that when k was low (i.e., greater heterogeneity, more superspreading events), reducing random sector contacts had a far greater impact on the epidemic trajectory than did reducing regular contacts; when k was high (i.e., less heterogeneity, no superspreading events), that difference disappeared. These results suggest that overdispersion of COVID-19 transmission gives the virus an Achilles' heel: Reducing contacts between people who do not regularly meet would substantially reduce the pandemic, while reducing repeated contacts in defined social groups would be less effective.

Substrate curvature governs texture orientation in thin films of smectic block copolymers.

Self-assembly of ordered nanometer-scale patterns is interesting in itself, but its practical value depends on the ability to predict and control pattern formation. In this paper we demonstrate theoretically and numerically that engineering of extrinsic as well as intrinsic substrate geometry may provide such a controllable ordering mechanism for block copolymers films. We develop an effective two-dimensional model of thin films of striped-phase diblock copolymers on general curved substrates. The model is obtained as an expansion in the film thickness and thus takes the third dimension into account, which crucially allows us to predict the preferred orientations even in the absence of intrinsic curvature. We determine the minimum-energy textures on several curved surfaces and arrive at a general principle for using substrate curvature as an ordering field, namely that the stripes will tend to align along directions of maximal curvature.

Model to Link Cell Shape and Polarity with Organogenesis.

How do flat sheets of cells form gut and neural tubes? Across systems, several mechanisms are at play: cells wedge, form actomyosin cables, or intercalate. As a result, the cell sheet bends, and the tube elongates. It is unclear to what extent each mechanism can drive tube formation on its own. To address this question, we computationally probe if one mechanism, either cell wedging or intercalation, may suffice for the entire sheet-to-tube transition. Using a physical model with epithelial cells represented by polarized point particles, we show that either cell intercalation or wedging alone can be sufficient and that each can both bend the sheet and extend the tube. When working in parallel, the two mechanisms increase the robustness of the tube formation. The successful simulations of the key features in Drosophila salivary gland budding, sea urchin gastrulation, and mammalian neurulation support the generality of our results.