Respiratory disease contact patterns in the US are stable but heterogeneous.

Background: Contact plays a critical role in infectious disease transmission. Characterizing heterogeneity in contact patterns across individuals, time, and space is necessary to inform accurate estimates of transmission risk, particularly to explain superspreading, predict age differences in vulnerability, and inform social distancing policies. Current respiratory disease models often rely on data from the 2008 POLYMOD study conducted in Europe, which is now outdated and potentially unrepresentative of behavior in the US. We seek to understand the variation in contact patterns across spatial scales and demographic and social classifications, whether there is seasonality to contact patterns, and what social behavior looks like at baseline in the absence of an ongoing pandemic. Methods: We analyze spatiotemporal non-household contact patterns across 11 million survey responses from June 2020 - April 2021 post-stratified on age and gender to correct for sample representation. To characterize spatiotemporal heterogeneity in respiratory contact patterns at the county-week scale, we use generalized additive models. In the absence of pre-pandemic data on contact in the US, we also use a regression approach to produce baseline contact estimates to fill this gap. Findings: Although contact patterns varied over time during the pandemic, contact is relatively stable after controlling for disease. We find that the mean number of non-household contacts is spatially heterogeneous regardless of disease. There is additional heterogeneity across age, gender, race/ethnicity, and contact setting, with mean contact decreasing with age and lower in women. The contacts of white individuals and contacts at work or social events change the most under increased national incidence. Interpretation: We develop the first county-level estimates of non-pandemic contact rates for the US that can fill critical gaps in parameterizing disease models. Our results identify that spatiotemporal, demographic, and social heterogeneity in contact patterns is highly structured, informing the risk landscape of respiratory disease transmission in the US.

Integrating dynamical modeling and phylogeographic inference to characterize global influenza circulation.

Global seasonal influenza circulation involves a complex interplay between local (seasonality, demography, host immunity) and global factors (international mobility) shaping recurrent epidemic patterns. No studies so far have reconciled the two spatial levels, evaluating the coupling between national epidemics, considering heterogeneous coverage of epidemiological and virological data, integrating different data sources. We propose a novel combined approach based on a dynamical model of global influenza spread (GLEAM), integrating high-resolution demographic and mobility data, and a generalized linear model of phylogeographic diffusion that accounts for time-varying migration rates. Seasonal migration fluxes across global macro-regions simulated with GLEAM are tested as phylogeographic predictors to provide model validation and calibration based on genetic data. Seasonal fluxes obtained with a specific transmissibility peak time and recurrent travel outperformed the raw air-transportation predictor, previously considered as optimal indicator of global influenza migration. Influenza A subtypes supported autumn-winter reproductive number as high as 2.25 and an average immunity duration of 2 years. Similar dynamics were preferred by influenza B lineages, with a lower autumn-winter reproductive number. Comparing simulated epidemic profiles against FluNet data offered comparatively limited resolution power. The multiscale approach enables model selection yielding a novel computational framework for describing global influenza dynamics at different scales - local transmission and national epidemics vs. international coupling through mobility and imported cases. Our findings have important implications to improve preparedness against seasonal influenza epidemics. The approach can be generalized to other epidemic contexts, such as emerging disease outbreaks to improve the flexibility and predictive power of modeling.

The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Underdetected dispersal and extensive local transmission drove the 2022 mpox epidemic.

The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control.

Drivers and impact of the early silent invasion of SARS-CoV-2 Alpha.

SARS-CoV-2 variants of concern (VOCs) circulated cryptically before being identified as a threat, delaying interventions. Here we studied the drivers of such silent spread and its epidemic impact to inform future response planning. We focused on Alpha spread out of the UK. We integrated spatio-temporal records of international mobility, local epidemic growth and genomic surveillance into a Bayesian framework to reconstruct the first three months after Alpha emergence. We found that silent circulation lasted from days to months and decreased with the logarithm of sequencing coverage. Social restrictions in some countries likely delayed the establishment of local transmission, mitigating the negative consequences of late detection. Revisiting the initial spread of Alpha supports local mitigation at the destination in case of emerging events.

SARS-CoV-2 infection prevalence and associated factors among primary healthcare workers in France after the third COVID-19 wave.

Data on the SARS-CoV-2 infection among primary health care workers (PHCWs) are scarce but essential to reflect on policy regarding prevention and control measures. We assessed the prevalence of PHCWs who have been infected by SARS-CoV-2 in comparison with modeling from the general population in metropolitan France, and associated factors. A cross-sectional study was conducted among general practitioners (GPs), pediatricians, dental and pharmacy workers in primary care between May and August 2021. Participants volunteered to provide a dried-blood spot for SARS-CoV-2 antibody assessment and completed a questionnaire. The primary outcome was defined as the detection of infection-induced antibodies (anti-nucleocapsid IgG, and for non-vaccinees: anti-Spike IgG and neutralizing antibodies) or previous self-reported infection (positive RT-qPCR or antigenic test, or positive ELISA test before vaccination). Estimates were adjusted using weights for representativeness and compared with prediction from the general population. Poisson regressions were used to quantify associated factors. The analysis included 1612 PHCWs. Weighted prevalences were: 31.7% (95% CI 27.5-36.0) for GPs, 28.7% (95% CI 24.4-33.0) for pediatricians, 25.2% (95% CI 20.6-31.0) for dentists, and 25.5% (95% CI 18.2-34.0) for pharmacists. Estimates were compatible with model predictions for the general population. PHCWs more likely to be infected were: GPs compared to pharmacist assistants (adjusted prevalence ratio [aPR] = 2.26; CI 95% 1.01-5.07), those living in Île-de-France (aPR = 1.53; CI 95% 1.14-2.05), South-East (aPR = 1.57; CI 95% 1.19-2.08), North-East (aPR = 1.81; CI 95% 1.38-2.37), and those having an unprotected contact with a COVID-19 case within the household (aPR = 1.48; CI 95% 1.22-1.80). Occupational factors were not associated with infection. In conclusion, the risk of SARS-CoV-2 exposure for PHCWs was more likely to have occurred in the community rather than at their workplace.

Dispersion patterns of SARS-CoV-2 variants Gamma, Lambda and Mu in Latin America and the Caribbean.

Latin America and Caribbean (LAC) regions were an important epicenter of the COVID-19 pandemic and SARS-CoV-2 evolution. Through the COVID-19 Genomic Surveillance Regional Network (COVIGEN), LAC countries produced an important number of genomic sequencing data that made possible an enhanced SARS-CoV-2 genomic surveillance capacity in the Americas, paving the way for characterization of emerging variants and helping to guide the public health response. In this study we analyzed approximately 300,000 SARS-CoV-2 sequences generated between February 2020 and March 2022 by multiple genomic surveillance efforts in LAC and reconstructed the diffusion patterns of the main variants of concern (VOCs) and of interest (VOIs) possibly originated in the Region. Our phylogenetic analysis revealed that the spread of variants Gamma, Lambda and Mu reflects human mobility patterns due to variations of international air passenger transportation and gradual lifting of social distance measures previously implemented in countries. Our results highlight the potential of genetic data to reconstruct viral spread and unveil preferential routes of viral migrations that are shaped by human mobility patterns.

The impact of spatial connectivity on NPIs effectiveness.

BACKGROUND: France implemented a combination of non-pharmaceutical interventions (NPIs) to manage the COVID-19 pandemic between September 2020 and June 2021. These included a lockdown in the fall 2020 - the second since the start of the pandemic - to counteract the second wave, followed by a long period of nighttime curfew, and by a third lockdown in the spring 2021 against the Alpha wave. Interventions have so far been evaluated in isolation, neglecting the spatial connectivity between regions through mobility that may impact NPI effectiveness. METHODS: Focusing on September 2020-June 2021, we developed a regionally-based epidemic metapopulation model informed by observed mobility fluxes from daily mobile phone data and fitted the model to regional hospital admissions. The model integrated data on vaccination and variants spread. Scenarios were designed to assess the impact of the Alpha variant, characterized by increased transmissibility and risk of hospitalization, of the vaccination campaign and alternative policy decisions. RESULTS: The spatial model better captured the heterogeneity observed in the regional dynamics, compared to models neglecting inter-regional mobility. The third lockdown was similarly effective to the second lockdown after discounting for immunity, Alpha, and seasonality (51% vs 52% median regional reduction in the reproductive number R0, respectively). The 6pm nighttime curfew with bars and restaurants closed, implemented in January 2021, substantially reduced COVID-19 transmission. It initially led to 49% median regional reduction of R0, decreasing to 43% reduction by March 2021. In absence of vaccination, implemented interventions would have been insufficient against the Alpha wave. Counterfactual scenarios proposing a sequence of lockdowns in a stop-and-go fashion would have reduced hospitalizations and restriction days for low enough thresholds triggering and lifting restrictions. CONCLUSIONS: Spatial connectivity induced by mobility impacted the effectiveness of interventions especially in regions with higher mobility rates. Early evening curfew with gastronomy sector closed allowed authorities to delay the third wave. Stop-and-go lockdowns could have substantially lowered both healthcare and societal burdens if implemented early enough, compared to the observed application of lockdown-curfew-lockdown, but likely at the expense of several labor sectors. These findings contribute to characterize the effectiveness of implemented strategies and improve pandemic preparedness.

Epidemic graph diagrams as analytics for epidemic control in the data-rich era.

COVID-19 highlighted modeling as a cornerstone of pandemic response. But it also revealed that current models may not fully exploit the high-resolution data on disease progression, epidemic surveillance and host behavior, now available. Take the epidemic threshold, which quantifies the spreading risk throughout epidemic emergence, mitigation, and control. Its use requires oversimplifying either disease or host contact dynamics. We introduce the epidemic graph diagrams to overcome this by computing the epidemic threshold directly from arbitrarily complex data on contacts, disease and interventions. A grammar of diagram operations allows to decompose, compare, simplify models with computational efficiency, extracting theoretical understanding. We use the diagrams to explain the emergence of resistant influenza variants in the 2007-2008 season, and demonstrate that neglecting non-infectious prodromic stages of sexually transmitted infections biases the predicted epidemic risk, compromising control. The diagrams are general, and improve our capacity to respond to present and future public health challenges.