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During the first phase of the COVID-19 epidemic, New York City rapidly became the epicenter of the pandemic in the United States. While molecular phylogenetic analyses have previously highlighted multiple introductions and a period of cryptic community transmission within New York City, little is known about the circulation of SARS-CoV-2 within and among its boroughs. We here perform phylogeographic investigations to gain insights into the circulation of viral lineages during the first months of the New York City outbreak. Our analyses describe the dispersal dynamics of viral lineages at the state and city levels, illustrating that peripheral samples likely correspond to distinct dispersal events originating from the main metropolitan city areas. In line with the high prevalence recorded in this area, our results highlight the relatively important role of the borough of Queens as a transmission hub associated with higher local circulation and dispersal of viral lineages toward the surrounding boroughs.

The recently emerged Omicron variant of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) (1) is highly transmissible and partially immune evasive (2). Omicron contributes to the recent surges in coronavirus disease [...]

Introduction The novel betacoronavirus SARS-CoV-2 arose as a new human pathogen at the end of 2019, and rapidly spread to every corner of the globe, causing a pandemic of enormous [...], The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February-April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in [chi square] and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations.

Abbreviation Introduction Based on the latest HIV molecular surveillance report, recombinant forms account for almost every fourth HIV infection globally (22.8%). Circulating recombinant form (CRF) 02_AG (CRF02_AG) is the most [...], : Introduction: In Cameroon, a manifold diversity of HIV strains exists with CRF02_AG and unique recombinant forms (URFs) being the predominant strains. In recent years, a steady increase in URFs and clade F2 viruses has been monitored through partial genome sequencing. There is an information gap in the characterization of emerging URFs along the full genome, which is needed to address the challenges URFs pose towards diagnosis, treatment and HIV?1 vaccine design. Method: Eighteen Cameroonian URFs from samples collected between the years 2000 and 2015 were studied using a newly developed near full genome sequencing (NFGS) protocol based on variable nested RT?PCRs with a versatile primer set. Near full genomes were characterized for recombination patterns and sequence signatures with possible impact on antiretroviral treatment or Env?directed immune responses. Third?generation sequencing (3GS) of near full or half genomes (HGs) gave insight into intra?patient URF diversity. Results: The characterized URFs were composed of a broad variety of subtypes and recombinants including A, F, G, CRF01_AE, CRF02_AG and CRF22_01A1. Phylogenetic analysis unveiled dominant CRF02_AG and F2 recombination patterns. 3GS indicated a high intra?patient URF diversity with up to four distinct viral sub?populations present in plasma at the same time. URF pol genomic analysis revealed a number of accessory drug resistance mutations (DRMs) in the ART?naïve participants. Genotypic env analysis suggests CCR5 usage in 14/18 samples and identified deviations at residues, critical for gp120/gp41 interphase and CD4 binding site broadly neutralizing antibodies in more than half of the studied URFs. V1V2 sites of immune pressure in the human RV144 vaccine study varied in more than a third of URFs. Conclusions: This study identified novel mosaic patterns in URFs in Cameroon. In line with the regional predominance of CRF_02AG and the increased prevalence of clade F2, prominent CRF_02AG and F2 background patterns were observed underlying the URFs. In the context of the novel mosaic genomes, the impact of the identified accessory DRMs and Env epitope variations on treatment and immune control remains elusive. The evolving diversity of HIV?1 URFs in Cameroon requires continuous monitoring to respond to the increasing challenges for diagnosis, antiretroviral treatment and prevention.

CTCF-mediated chromatin folding plays a key role in gene regulation, however the mechanisms underlying cell type-specific control are not fully elucidated. Comprehensive analyses reveal that CTCF binding stability and cohesin overlap in mice and humans is regulated by species specific differences in accessibility, the presence of CTCF extended Up and Downstream binding site sequences and motifs corresponding to expressed TFs enriched at most bound sites. CTCF repositions nucleosomes asymmetrically, with linker spacing altered by accessibility, while cohesin-mediated nucleosome phasing is affected by surrounding motifs that similarly impact chromatin insulation. Importantly, cell type-specific transcriptional programs determine motif enrichment at CTCF bound sites, reflecting the stabilizing/destabilizing effect of individual TFs. These studies identify mechanisms underlying cell type-specific CTCF profiles, linked to local and long-range chromatin organization.

Background: The emergence of recombinant viruses is a threat to public health. Recombination of viral variants may combine variant-specific features that together catalyze viral escape from treatment or immunity. The selective advantages of recombinant SARS-CoV-2 isolates over their parental lineages remain unknown., Methods: Multi-method amplicon and metagenomic sequencing of a clinical swab and the in vitro grown virus allowed for high-confidence detection of a novel recombinant variant. Mutational, phylogeographic, and structural analyses determined features of the recombinant genome and spike protein. Neutralization assays using infectious as well as pseudotyped viruses and point mutants thereof defined the recombinant's sensitivity to a panel of monoclonal antibodies and sera from vaccinated and/or convalescent individuals., Results: A novel Delta-Omicron SARS-CoV-2 recombinant was identified in an unvaccinated, immunosuppressed kidney transplant recipient treated with monoclonal antibody Sotrovimab. The recombination breakpoint is located in the spike N-terminal domain, adjacent to the Sotrovimab quaternary binding site, and results in a 5'-Delta AY.45 and a 3'-Omicron BA.1 mosaic spike protein. Delta and BA.1 are sensitive to Sotrovimab neutralization, whereas the Delta-Omicron recombinant is highly resistant to Sotrovimab, both with and without the RBD resistance mutation E340D., Conclusions: Recombination between circulating SARS-CoV-2 variants can functionally contribute to immune escape. It is critical to validate phenotypes of mosaic viruses and monitor immunosuppressed COVID-19 patients treated with monoclonal antibodies for the selection of recombinant and immune escape variants. (Funded by NYU, the National Institutes of Health, and others).

In 2021, Delta has become the predominant SARS-CoV-2 variant worldwide. While vaccines effectively prevent COVID-19 hospitalization and death, vaccine breakthrough infections increasingly occur. The precise role of clinical and genomic determinants in Delta infections is not known, and whether they contribute to increased rates of breakthrough infections compared to unvaccinated controls. Here, we show a steep and near complete replacement of circulating variants with Delta between May and August 2021 in metropolitan New York. We observed an increase of the Delta sublineage AY.25, its spike mutation S112L, and nsp12 mutation F192V in breakthroughs. Delta infections were associated with younger age and lower hospitalization rates than Alpha. Delta breakthroughs increased significantly with time since vaccination, and, after adjusting for confounders, they rose at similar rates as in unvaccinated individuals. Our data indicate a limited impact of vaccine escape in favor of Delta's increased epidemic growth in times of waning vaccine protection., Competing Interests: Conflict of Interest Statement: The authors declare that no conflict of interest exists

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

Effective public response to a pandemic relies upon accurate measurement of the extent and dynamics of an outbreak. Viral genome sequencing has emerged as a powerful approach to link seemingly unrelated cases, and large-scale sequencing surveillance can inform on critical epidemiological parameters. Here, we report the analysis of 864 SARS-CoV-2 sequences from cases in the New York City metropolitan area during the COVID-19 outbreak in Spring 2020. The majority of cases had no recent travel history or known exposure, and genetically linked cases were spread throughout the region. Comparison to global viral sequences showed that early transmission was most linked to cases from Europe. Our data are consistent with numerous seeds from multiple sources and a prolonged period of unrecognized community spreading. This work highlights the complementary role of genomic surveillance in addition to traditional epidemiological indicators., Competing Interests: Competing interest statement The authors declare no competing interests.