Local-scale phylodynamics reveal differential community impact of SARS-CoV-2 in a metropolitan US county.

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.

Associations Between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants and Risk of Coronavirus Disease 2019 (COVID-19) Hospitalization Among Confirmed Cases in Washington State: A Retrospective Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with 7 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. METHODS: Our study includes individuals with positive SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) in the Washington Disease Reporting System with available viral genome data, from 1 December 2020 to 14 January 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. RESULTS: In total, 58 848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95% confidence interval [CI] 2.40-4.26), Beta (HR 2.85, 95% CI 1.56-5.23), Delta (HR 2.28 95% CI 1.56-3.34), or Alpha (HR 1.64, 95% CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95% CI .56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSIONS: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences.

Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. 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. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.

Antiamoebic properties of the actinomycete metabolites echinomycin A and tirandamycin A.

Entamoeba histolytica infects 50 million people per year, causing 100,000 deaths worldwide. The primary treatment for amoebiasis is metronidazole. However, increased pathogen resistance combined with the drug's toxic side effects encourages a search for alternative therapeutic agents. Secondary metabolites from marine bacteria are a promising resource for antiprotozoan drug discovery. In this study, extracts from a collection of marine-derived actinomycetes were screened for antiamoebic properties, and the activities of antibiotics echinomycin A and tirandamycin A are shown. Both antibiotics inhibited the in vitro growth of a E. histolytica laboratory strain (HM-1:IMSS) and a clinical isolate (Colombia, Col) at 30- to 60-µM concentrations. EIC(50) (estimated inhibitory concentration) values were comparable for both antibiotics (44.3-46.3 µM) against the E. histolytica clinical isolate.

Local-Scale phylodynamics reveal differential community impact of SARS-CoV-2 in metropolitan US county.

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.

Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study.

BACKGROUND: The COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants. METHODS: Our study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination. FINDINGS: 58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination. CONCLUSION: Infection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance. SUMMARY: Hospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.

Viral genomes reveal patterns of the SARS-CoV-2 outbreak in Washington State.

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has gravely affected societies around the world. Outbreaks in different parts of the globe have been shaped by repeated introductions of new viral lineages and subsequent local transmission of those lineages. Here, we sequenced 3940 SARS-CoV-2 viral genomes from Washington State (USA) to characterize how the spread of SARS-CoV-2 in Washington State in early 2020 was shaped by differences in timing of mitigation strategies across counties and by repeated introductions of viral lineages into the state. In addition, we show that the increase in frequency of a potentially more transmissible viral variant (614G) over time can potentially be explained by regional mobility differences and multiple introductions of 614G but not the other variant (614D) into the state. At an individual level, we observed evidence of higher viral loads in patients infected with the 614G variant. However, using clinical records data, we did not find any evidence that the 614G variant affects clinical severity or patient outcomes. Overall, this suggests that with regard to D614G, the behavior of individuals has been more important in shaping the course of the pandemic in Washington State than this variant of the virus.

SARS-CoV-2 Epidemiology on a Public University Campus in Washington State.

BACKGROUND: We aimed to evaluate a testing program to facilitate control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission at a large university and measure spread in the university community using viral genome sequencing. METHODS: Our prospective longitudinal study used remote contactless enrollment, daily mobile symptom and exposure tracking, and self-swab sample collection. Individuals were tested if the participant was exposed to a known SARS-CoV-2-infected person, developed new symptoms, or reported high-risk behavior (such as attending an indoor gathering without masking or social distancing), if a member of a group experiencing an outbreak, or at enrollment. Study participants included students, staff, and faculty at an urban public university during the Autumn quarter of 2020. RESULTS: We enrolled 16 476 individuals, performed 29 783 SARS-CoV-2 tests, and detected 236 infections. Seventy-five percent of positive cases reported at least 1 of the following: symptoms (60.8%), exposure (34.7%), or high-risk behaviors (21.5%). Greek community affiliation was the strongest risk factor for testing positive, and molecular epidemiology results suggest that specific large gatherings were responsible for several outbreaks. CONCLUSIONS: A testing program focused on individuals with symptoms and unvaccinated persons who participate in large campus gatherings may be effective as part of a comprehensive university-wide mitigation strategy to control the spread of SARS-CoV-2.

Viral genomes reveal patterns of the SARS-CoV-2 outbreak in Washington State.

The rapid spread of SARS-CoV-2 has gravely impacted societies around the world. Outbreaks in different parts of the globe are shaped by repeated introductions of new lineages and subsequent local transmission of those lineages. Here, we sequenced 3940 SARS-CoV-2 viral genomes from Washington State to characterize how the spread of SARS-CoV-2 in Washington State (USA) was shaped by differences in timing of mitigation strategies across counties, as well as by repeated introductions of viral lineages into the state. Additionally, we show that the increase in frequency of a potentially more transmissible viral variant (614G) over time can potentially be explained by regional mobility differences and multiple introductions of 614G, but not the other variant (614D) into the state. At an individual level, we see evidence of higher viral loads in patients infected with the 614G variant. However, using clinical records data, we do not find any evidence that the 614G variant impacts clinical severity or patient outcomes. Overall, this suggests that at least to date, the behavior of individuals has been more important in shaping the course of the pandemic than changes in the virus.