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Pathogen genomics can provide insights into underlying infectious disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets and realize this full potential. In particular, genetically proximal viruses should be highly informative about transmission events as genetic proximity indicates epidemiological linkage. Here, we leverage pairs of identical sequences to characterise fine-scale transmission patterns using 114,298 SARS-CoV-2 genomes collected through Washington State (USA) genomic sentinel surveillance with associated age and residence location information between March 2021 and December 2022. This corresponds to 59,660 sequences with another identical sequence in the dataset. We find that the location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. We find that transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. Overall, this work improves our ability to leverage large pathogen genome datasets to understand the determinants of infectious disease spread., Competing Interests: ALG reports contract testing from Abbott, Cepheid, Novavax, Pfizer, Janssen and Hologic, research support from Gilead, and salary and stock grants for LabCorp an immediate family member, outside of the described work. All other authors declare no competing interests.

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity., Competing Interests: AP, JH, JB, TR, XX, RK, DW, NL, LW, BE, RH, MG, RD, SF, KN, NK, SW, HH, TB No competing interests declared, CH Received personal fees from Sanofi outside the submitted work, JM Received consulting fees, honoraria, and travel support from Sanofi Pasteur and Sequris, SS The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne has a collaborative research and development agreement (CRADA) with CSL Seqirus for isolation of candidate vaccine viruses in cells and an agreement with IFPMA for isolation of candidate vaccine viruses in eggs. SGS reports honoraria from CSL Seqirus, Moderna, Pfizer, and Evo Health, IB, KS The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne has a collaborative research and development agreement (CRADA) with CSL Seqirus for isolation of candidate vaccine viruses in cells and an agreement with IFPMA for isolation of candidate vaccine viruses in eggs, FK The Icahn School of Medicine at Mount Sinai has filed patent applications relating to influenza virus vaccines (U.S. patent numbers: 12030928, 11865173, 11266734, 11254733, 10736956, 10583188, 10137189, 10131695, 9968670, 9371366; publication numbers: 20230181715, 20220403358, 20220249652, 20220242935, 20220153873, 20210260179, 20190125859, 20190106461, 20180333479), SARS-CoV-2 serological assays (publication number: 20240210415), and SARS-CoV-2 vaccines (publication numbers: 20230310583, 20230226171), which list FK as co-inventor. FK has consulted for Merck and Pfizer (before 2020), and is currently consulting for Pfizer, Seqirus, 3rd Rock Ventures, GSK and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS‐CoV‐2 and with Dynavax on universal influenza virus vaccines, CV Received honoraria for serving as an Editor in Chief of the journal Epidemics (Elsevier)

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2 nd most accurate model measured by WIS in 2021-22 and the 5 th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection dynamics, presumably via heterosubtypic cross-immunity., Competing Interests: Competing interests The WHO Collaborating Centre for Reference and Research on Influenza in Melbourne has a collaborative research and development agreement (CRADA) with CSL Seqirus for isolation of candidate vaccine viruses in cells and an agreement with IFPMA for isolation of candidate vaccine viruses in eggs. SGS reports honoraria from CSL Seqirus, Moderna, Pfizer, and Evo Health. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to influenza virus vaccines, SARS-CoV-2 serological assays, and SARS-CoV-2 vaccines which list FK as co-inventor. Mount Sinai has spun out companies, Kantaro and Castlevax, to market the SARS-CoV-2 related technologies. FK has consulted for Merck and Pfizer (before 2020), and is currently consulting for Pfizer, Seqirus, 3rd Rock Ventures, GSK and Avimex. The Krammer laboratory is also collaborating with Pfizer on animal models of SARS-CoV-2 and with Dynavax on universal influenza virus vaccines. All other authors declare no competing interests.

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves., (© 2024. The Author(s).)

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape., Competing Interests: ALG reported receiving contract testing from Abbott, Cepheid, Novavax, Pfizer, Janssen and Hologic and research support from Gilead and Merck, outside of the described work. HC reported consulting with Ellume, Pfizer, the Bill & Melinda Gates Foundation, Glaxo Smith Kline, and Merck. She has received research funding from Emergent Ventures, Gates Ventures, Sanofi Pasteur, the Bill & Melinda Gates Foundation, and research support and reagents from Ellume and Cepheid outside of the submitted work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All other authors declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Importance: Few US studies have reexamined risk factors for SARS-CoV-2 positivity in the context of widespread vaccination and new variants or considered risk factors for cocirculating endemic viruses, such as rhinovirus., Objectives: To evaluate how risk factors and symptoms associated with SARS-CoV-2 test positivity changed over the course of the pandemic and to compare these with the risk factors associated with rhinovirus test positivity., Design, Setting, and Participants: This case-control study used a test-negative design with multivariable logistic regression to assess associations between SARS-CoV-2 and rhinovirus test positivity and self-reported demographic and symptom variables over a 25-month period. The study was conducted among symptomatic individuals of all ages enrolled in a cross-sectional community surveillance study in King County, Washington, from June 2020 to July 2022., Exposures: Self-reported data for 15 demographic and health behavior variables and 16 symptoms., Main Outcomes and Measures: Reverse transcription-polymerase chain reaction-confirmed SARS-CoV-2 or rhinovirus infection., Results: Analyses included data from 23 498 individuals. The median (IQR) age of participants was 34.33 (22.42-45.08) years, 13 878 (59.06%) were female, 4018 (17.10%) identified as Asian, 654 (2.78%) identified as Black, and 2193 (9.33%) identified as Hispanic. Close contact with an individual with SARS-CoV-2 (adjusted odds ratio [aOR], 3.89; 95% CI, 3.34-4.57) and loss of smell or taste (aOR, 3.49; 95% CI, 2.77-4.41) were the variables most associated with SARS-CoV-2 test positivity, but both attenuated during the Omicron period. Contact with a vaccinated individual with SARS-CoV-2 (aOR, 2.03; 95% CI, 1.56-2.79) was associated with lower odds of testing positive than contact with an unvaccinated individual with SARS-CoV-2 (aOR, 4.04; 95% CI, 2.39-7.23). Sore throat was associated with Omicron infection (aOR, 2.27; 95% CI, 1.68-3.20) but not Delta infection. Vaccine effectiveness for participants fully vaccinated with a booster dose was 93% (95% CI, 73%-100%) for Delta, but not significant for Omicron. Variables associated with rhinovirus test positivity included being younger than 12 years (aOR, 3.92; 95% CI, 3.42-4.51) and experiencing a runny or stuffy nose (aOR, 4.58; 95% CI, 4.07-5.21). Black race, residing in south King County, and households with 5 or more people were significantly associated with both SARS-CoV-2 and rhinovirus test positivity., Conclusions and Relevance: In this case-control study of 23 498 symptomatic individuals, estimated risk factors and symptoms associated with SARS-CoV-2 infection changed over time. There was a shift in reported symptoms between the Delta and Omicron variants as well as reductions in the protection provided by vaccines. Racial and sociodemographic disparities persisted in the third year of SARS-CoV-2 circulation and were also present in rhinovirus infection. Trends in testing behavior and availability may influence these results.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused severe disruptions to healthcare in many areas of the world, but data remain scarce for sub-Saharan Africa., Methods: We evaluated trends in hospital admissions and outpatient emergency department (ED) and general practitioner (GP) visits to South Africa's largest private healthcare system during 2016-2021. We fit time series models to historical data and, for March 2020-September 2021, quantified changes in encounters relative to baseline., Results: The nationwide lockdown on 27 March 2020 led to sharp reductions in care-seeking behavior that persisted for 18 months after initial declines. For example, total admissions dropped 59.6% (95% confidence interval [CI], 52.4-66.8) during home confinement and were 33.2% (95% CI, 29-37.4) below baseline in September 2021. We identified 3 waves of all-cause respiratory encounters consistent with COVID-19 activity. Intestinal infections and non-COVID-19 respiratory illnesses experienced the most pronounced declines, with some diagnoses reduced 80%, even as nonpharmaceutical interventions (NPIs) relaxed. Non-respiratory hospitalizations, including injuries and acute illnesses, were 20%-60% below baseline throughout the pandemic and exhibited strong temporal associations with NPIs and mobility. ED attendances exhibited trends similar to those for hospitalizations, while GP visits were less impacted and have returned to pre-pandemic levels., Conclusions: We found substantially reduced use of health services during the pandemic for a range of conditions unrelated to COVID-19. Persistent declines in hospitalizations and ED visits indicate that high-risk patients are still delaying seeking care, which could lead to morbidity or mortality increases in the future., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.)

Primates acquire gut microbiota from conspecifics through direct social contact and shared environmental exposures. Host behaviour is a prominent force in structuring gut microbial communities, yet the extent to which group or individual-level forces shape the long-term dynamics of gut microbiota is poorly understood. We investigated the effects of three aspects of host sociality (social groupings, dyadic interactions, and individual dispersal between groups) on gut microbiome composition and plasticity in 58 wild Verreaux's sifaka (Propithecus verreauxi) from six social groups. Over the course of three dry seasons in a 5-year period, the six social groups maintained distinct gut microbial signatures, with the taxonomic composition of individual communities changing in tandem among coresiding group members. Samples collected from group members during each season were more similar than samples collected from single individuals across different years. In addition, new immigrants and individuals with less stable social ties exhibited elevated rates of microbiome turnover across seasons. Our results suggest that permanent social groupings shape the changing composition of commensal and mutualistic gut microbial communities and thus may be important drivers of health and resilience in wild primate populations., (© 2021 John Wiley & Sons Ltd.)

Background: Since 2011, influenza A viruses circulating in US swine exhibited at county fairs are associated with >460 zoonotic infections, presenting an ongoing pandemic risk. Swine "jackpot shows" that occur before county fairs each summer intermix large numbers of exhibition swine from diverse geographic locations. We investigated the role of jackpot shows in influenza zoonoses., Methods: We collected snout wipe or nasal swab samples from 17 009 pigs attending 350 national, state, and local swine exhibitions across 8 states during 2016-2018., Results: Influenza was detected in 13.9% of swine sampled at jackpot shows, and 76.3% of jackpot shows had at least 1 pig test positive. Jackpot shows had 4.3-fold higher odds of detecting at least 1 influenza-positive pig compared to county fairs. When influenza was detected at a county fair, almost half of pigs tested positive, clarifying why zoonotic infections occur primarily at county fairs., Conclusions: The earlier timing of jackpot shows and long-distance travel for repeated showing of individual pigs provide a pathway for the introduction of influenza into county fairs. Mitigation strategies aimed at curtailing influenza at jackpot shows are likely to have downstream effects on disease transmission at county fairs and zoonoses., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

New measures of influenza virus fitness could improve vaccine strain selection through more accurate forecasts of the evolution of the virus., Competing Interests: AP, MN No competing interests declared

The gut microbiomes of mammals appear to mirror their hosts' phylogeny, suggesting host-driven microbial community assembly. Yet, much of this evidence stems from comparative studies of distinct wild or captive populations that lack data for disentangling the relative influences of shared phylogeny and environment. Here, we present phylogenetic and multivariate analyses of gut microbiomes from six sympatric (i.e., co-occurring) mammal species inhabiting a 1-km 2 area in western Madagascar-three lemur and three non-primate species-that consider genetic, dietary, and ecological predictors of microbiome functionality and composition. Host evolutionary history, indeed, appears to shape gut microbial patterns among both closely and distantly related species. However, we also find that diet-reliance on leaves versus fruit-is the best predictor of microbiome similarity among closely related lemur species, and that host substrate use-ground versus tree-constrains horizontal transmission via incidental contact with feces, with arboreal species harboring far more distinct communities than those of their terrestrial and semi-terrestrial counterparts.

In wild primates, social behaviour influences exposure to environmentally acquired and directly transmitted microorganisms. Prior studies indicate that gut microbiota reflect pairwise social interactions among chimpanzee and baboon hosts. Here, we demonstrate that higher-order social network structure-beyond just pairwise interactions-drives gut bacterial composition in wild lemurs, which live in smaller and more cohesive groups than previously studied anthropoid species. Using 16S rRNA gene sequencing and social network analysis of grooming contacts, we estimate the relative impacts of hierarchical (i.e. multilevel) social structure, individual demographic traits, diet, scent-marking, and habitat overlap on bacteria acquisition in a wild population of Verreaux's sifaka ( Propithecus verreauxi ) consisting of seven social groups. We show that social group membership is clearly reflected in the microbiomes of individual sifaka, and that social groups with denser grooming networks have more homogeneous gut microbial compositions. Within social groups, adults, more gregarious individuals, and individuals that scent-mark frequently harbour the greatest microbial diversity. Thus, the community structure of wild lemurs governs symbiotic relationships by constraining transmission between hosts and partitioning environmental exposure to microorganisms. This social cultivation of mutualistic gut flora may be an evolutionary benefit of tight-knit group living., (© 2017 The Author(s).)

Knowledge of the key resources for a species is critical for developing an effective conservation strategy. Kirindy Mitea National Park is an important refuge for the red-tailed sportive lemur (Lepilemur ruficaudatus), a nocturnal folivorous lemur endemic to the dry deciduous forest of western Madagascar. Because L. ruficaudatus sleeps in tree holes during the day, sleeping trees may be an important resource for this species. Our goal was to characterize the sleeping sites used by L. ruficaudatus at the Ankoatsifaka Research Station in Kirindy Mitea National Park. In July and August 2012, tree characteristics were recorded for 60 L. ruficaudatus sleeping sites. Intact and alive trees, particularly Strychnos madagascariensis, were preferred by L. ruficaudatus. Sleeping holes were generally located in taller trees (median hole height = 4 m) and in trees with large girths (median = 20.5 cm). Greater protection from predators and thermal shifts may be provided by intact trees and concealed tree holes. Because tree characteristics can influence the presence and abundance of forest-living primates, the availability and characteristics of particular trees as potential sleeping shelters in a habitat must be taken into account in conservation strategies for L. ruficaudatus., (© 2017 S. Karger AG, Basel.)

While vector-borne diseases are known to be particularly influenced by environmental factors, the impact of land-cover change on vector-borne wildlife disease patterns is poorly understood, largely due to the paucity of data on disease occurrence at extensive spatial and temporal scales. Widespread and rapid anthropogenic land-cover change, especially urbanization, has transformed the US landscape during the last century. Epizootic hemorrhagic disease virus and blue tongue virus, vectored by Culicoides biting midges, are two RNA viruses in the Orbivirus genus that cause severe hemorrhagic disease (HD) in white-tailed deer (Odocoileus virginianus). We examine the spatial dynamics of HD affecting white-tailed deer in the contiguous United States in two periods covering 1980 to 2007 in connection with land-cover change over the same time. Using spatial statistical modeling, wetland cover emerges as a critical driver of HD morbidity, whereas the drivers of mortality patterns are more complex. Increasing wetland cover is positively associated with HD morbidity, which is consistent with the ecologic requirements of the Culicoides vector. Wetland cover is inherently dynamic due to its importance to biodiversity and water quality as well as its utility for other purposes when drained. Accordingly this analysis helps in understanding the consequences of changing wetlands on vector-borne disease patterns, to identify disease hotspots in a large landscape, and to forecast the spatial spread of HD and related diseases.