Quantifying individual-level heterogeneity in infectiousness and susceptibility through household studies.

The spread of SARS-CoV-2, like that of many other pathogens, is governed by heterogeneity. "Superspreading," or "over-dispersion," is an important factor in transmission, yet it is hard to quantify. Estimates from contact tracing data are prone to potential biases due to the increased likelihood of detecting large clusters of cases, and may reflect variation in contact behavior more than biological heterogeneity. In contrast, the average number of secondary infections per contact is routinely estimated from household surveys, and these studies can minimize biases by testing all members of a household. However, the models used to analyze household transmission data typically assume that infectiousness and susceptibility are the same for all individuals or vary only with predetermined traits such as age. Here we develop and apply a combined forward simulation and inference method to quantify the degree of inter-individual variation in both infectiousness and susceptibility from observations of the distribution of infections in household surveys. First, analyzing simulated data, we show our method can reliably ascertain the presence, type, and amount of these heterogeneities given data from a sufficiently large sample of households. We then analyze a collection of household studies of COVID-19 from diverse settings around the world, and find strong evidence for large heterogeneity in both the infectiousness and susceptibility of individuals. Our results also provide a framework to improve the design of studies to evaluate household interventions in the presence of realistic heterogeneity between individuals.

Quantifying individual-level heterogeneity in infectiousness and susceptibility through household studies.

The spread of SARS-CoV-2, like that of many other pathogens, is governed by heterogeneity. "Superspreading," or "over-dispersion," is an important factor in transmission, yet it is hard to quantify. Estimates from contact tracing data are prone to potential biases due to the increased likelihood of detecting large clusters of cases, and may reflect variation in contact behavior more than biological heterogeneity. In contrast, the average number of secondary infections per contact is routinely estimated from household surveys, and these studies can minimize biases by testing all members of a household. However, the models used to analyze household transmission data typically assume that infectiousness and susceptibility are the same for all individuals or vary only with predetermined traits such as age. Here we develop and apply a combined forward simulation and inference method to quantify the degree of inter-individual variation in both infectiousness and susceptibility from observations of the distribution of infections in household surveys. First, analyzing simulated data, we show our method can reliably ascertain the presence, type, and amount of these heterogeneities with data from a sufficiently large sample of households. We then analyze a collection of household studies of COVID-19 from diverse settings around the world, and find strong evidence for large heterogeneity in both the infectiousness and susceptibility of individuals. Our results also provide a framework to improve the design of studies to evaluate household interventions in the presence of realistic heterogeneity between individuals.

The risk of drug resistance during long-acting antimicrobial therapy.

The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, and tuberculosis. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New long-acting drugs are being developed for weekly, monthly or less frequent dosing to improve adherence, but may lead to long-term exposure to intermediate drug levels. In this study, we analyse the effect of dosing frequency on the risk of resistance evolving during time-varying drug levels. We find that long-acting therapies can increase, decrease or have little effect on resistance, depending on the source (pre-existing or de novo) and degree of resistance, and rates of drug absorption and clearance. Long-acting therapies with rapid drug absorption, slow clearance and strong wild-type inhibition tend to reduce resistance caused by partially resistant strains in the early stages of treatment even if they do not improve adherence. However, if subpopulations of microbes persist and can reactivate during sub-optimal treatment, longer-acting therapies may substantially increase the resistance risk. Our results show that drug kinetics affect selection for resistance in a complicated manner, and that pathogen-specific models are needed to evaluate the benefits of new long-acting therapies.

A Systematic Review of Coronavirus Disease 2019 Vaccine Efficacy and Effectiveness Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Disease.

Billions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, dramatically reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) incidence and severity in some settings. Many studies suggest vaccines provide a high degree of protection against infection and disease, but precise estimates vary and studies differ in design, outcomes measured, dosing regime, location, and circulating virus strains. In this study, we conduct a systematic review of COVID-19 vaccines through February 2022. We included efficacy data from Phase 3 clinical trials for 15 vaccines undergoing World Health Organization Emergency Use Listing evaluation and real-world effectiveness for 8 vaccines with observational studies meeting inclusion criteria. Vaccine metrics collected include protection against asymptomatic infection, any infection, symptomatic COVID-19, and severe outcomes including hospitalization and death, for partial or complete vaccination, and against variants of concern Alpha, Beta, Gamma, Delta, and Omicron. We additionally review the epidemiological principles behind the design and interpretation of vaccine efficacy and effectiveness studies, including important sources of heterogeneity.

Bottlenecks, Modularity, and the Neural Control of Behavior.

In almost all animals, the transfer of information from the brain to the motor circuitry is facilitated by a relatively small number of neurons, leading to a constraint on the amount of information that can be transmitted. Our knowledge of how animals encode information through this pathway, and the consequences of this encoding, however, is limited. In this study, we use a simple feed-forward neural network to investigate the consequences of having such a bottleneck and identify aspects of the network architecture that enable robust information transfer. We are able to explain some recently observed properties of descending neurons-that they exhibit a modular pattern of connectivity and that their excitation leads to consistent alterations in behavior that are often dependent upon the desired behavioral state of the animal. Our model predicts that in the presence of an information bottleneck, such a modular structure is needed to increase the efficiency of the network and to make it more robust to perturbations. However, it does so at the cost of an increase in state-dependent effects. Despite its simplicity, our model is able to provide intuition for the trade-offs faced by the nervous system in the presence of an information processing constraint and makes predictions for future experiments.

The effect of eviction moratoria on the transmission of SARS-CoV-2.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.

Dynamics of COVID-19 under social distancing measures are driven by transmission network structure.

In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. Our simulations show that long delays between the adoption of control measures and observed declines in cases, hospitalizations, and deaths occur in many scenarios. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. We suggest limited conditions under which the formation of household "bubbles" can be safe. These findings can improve future predictions of the timescale and efficacy of interventions needed to control second waves of COVID-19 as well as other similar outbreaks, and highlight the need for better quantification and control of household transmission.

The effect of eviction moratoria on the transmission of SARS-CoV-2.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess municipal eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.

Dynamics of COVID-19 under social distancing measures are driven by transmission network structure.

In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. Our simulations show that long delays between the adoption of control measures and observed declines in cases, hospitalizations, and deaths occur in many scenarios. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. We suggest limited conditions under which the formation of household "bubbles" can be safe. These findings can improve future predictions of the timescale and efficacy of interventions needed to control second waves of COVID-19 as well as other similar outbreaks, and highlight the need for better quantification and control of household transmission.

Crowding and the shape of COVID-19 epidemics.

The coronavirus disease 2019 (COVID-19) pandemic is straining public health systems worldwide, and major non-pharmaceutical interventions have been implemented to slow its spread1-4. During the initial phase of the outbreak, dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was primarily determined by human mobility from Wuhan, China5,6. Yet empirical evidence on the effect of key geographic factors on local epidemic transmission is lacking7. In this study, we analyzed highly resolved spatial variables in cities, together with case count data, to investigate the role of climate, urbanization and variation in interventions. We show that the degree to which cases of COVID-19 are compressed into a short period of time (peakedness of the epidemic) is strongly shaped by population aggregation and heterogeneity, such that epidemics in crowded cities are more spread over time, and crowded cities have larger total attack rates than less populated cities. Observed differences in the peakedness of epidemics are consistent with a meta-population model of COVID-19 that explicitly accounts for spatial hierarchies. We paired our estimates with globally comprehensive data on human mobility and predict that crowded cities worldwide could experience more prolonged epidemics.