New York City (NYC) has emerged as one of the epicenters of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. To identify the early transmission events underlying the ...rapid spread of the virus in the NYC metropolitan area, we sequenced the virus that causes coronavirus disease 2019 (COVID-19) in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV-2 genomes indicates multiple, independent, but isolated introductions mainly from Europe and other parts of the United States. Moreover, we found evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.
The prolonged contagious period after viral infection in immunocompromised patients may affect how long precautions will be necessary to reduce further transmission. Replication-competent SARS-CoV-2 ...was detected for up to 61 days in patients who were immunocompromised by treatment for cancer.
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although ...intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
We performed phylogenomic analysis of severe acute respiratory syndrome coronavirus‐2 from 88 infected individuals across different regions of Colombia. Eleven different lineages were detected, ...suggesting multiple introduction events. Pangolin lineages B.1 and B.1.5 were the most frequent, with B.1 being associated with prior travel to high‐risk areas.
Highlights
This is the first genomic epidemiology study of SARS‐CoV2 in Colombia.
Craniofacial development depends on formation and maintenance of sutures between bones of the skull. In sutures, growth occurs at osteogenic fronts along the edge of each bone, and suture mesenchyme ...separates adjacent bones. Here, we perform single-cell RNA-seq analysis of the embryonic, wild type murine coronal suture to define its population structure. Seven populations at E16.5 and nine at E18.5 comprise the suture mesenchyme, osteogenic cells, and associated populations. Expression of Hhip, an inhibitor of hedgehog signaling, marks a mesenchymal population distinct from those of other neurocranial sutures. Tracing of the neonatal Hhip-expressing population shows that descendant cells persist in the coronal suture and contribute to calvarial bone growth. In Hhip
coronal sutures at E18.5, the osteogenic fronts are closely apposed and the suture mesenchyme is depleted with increased hedgehog signaling compared to those of the wild type. Collectively, these data demonstrate that Hhip is required for normal coronal suture development.
SARS-CoV-2 lineages have diverged into highly prevalent variants termed “variants of concern” (VOCs). Here, we characterized emerging SARS-CoV-2 spike polymorphisms in vitro and in vivo to understand ...their impact on transmissibility and virus pathogenicity and fitness. We demonstrate that the substitution S:655Y, represented in the gamma and omicron VOCs, enhances viral replication and spike protein cleavage. The S:655Y substitution was transmitted more efficiently than its ancestor S:655H in the hamster infection model and was able to outcompete S:655H in the hamster model and in a human primary airway system. Finally, we analyzed a set of emerging SARS-CoV-2 variants to investigate how different sets of mutations may impact spike processing. All VOCs tested exhibited increased spike cleavage and fusogenic capacity. Taken together, our study demonstrates that the spike mutations present in VOCs that become epidemiologically prevalent in humans are linked to an increase in spike processing and virus transmission.
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•The S:655Y mutation in SARS-CoV-2 enhances spike protein cleavage and fusogenicity•The S:655Y mutation increases transmissibility in vivo•S:655Y was able to outcompete ancestral S:655H in vivo•SARS-CoV-2 VOCs evolve to acquire an increased spike cleavage and fusogenic ability
Escalera et al. show that spike mutation H655Y, which is present in SARS-CoV-2 variants gamma and omicron, enhances spike protein cleavage, cell-cell fusion, and transmission in the hamster model. Additionally, SARS-CoV-2 variants of concern are shown to have independently acquired mutations associated with a gain in spike cleavage and syncytia formation.
The coronavirus disease 2019 (COVID‐19) pandemic has sparked the rapid development of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) diagnostics. However, emerging variants pose the ...risk for target dropout and false‐negative results secondary to primer/probe binding site (PBS) mismatches. The Agena MassARRAY® SARS‐CoV‐2 Panel combines reverse‐transcription polymerase chain reaction and matrix‐assisted laser desorption/ionization time‐of‐flight mass‐spectrometry to probe for five targets across N and ORF1ab genes, which provides a robust platform to accommodate PBS mismatches in divergent viruses. Herein, we utilize a deidentified data set of 1262 SARS‐CoV‐2‐positive specimens from Mount Sinai Health System (New York City) from December 2020 to April 2021 to evaluate target results and corresponding sequencing data. Overall, the level of PBS mismatches was greater in specimens with target dropout. Of specimens with N3 target dropout, 57% harbored an A28095T substitution that is highly specific for the Alpha (B.1.1.7) variant of concern. These data highlight the benefit of redundancy in target design and the potential for target performance to illuminate the dynamics of circulating SARS‐CoV‐2 variants.
Highlights
SARS‐CoV‐2 variation introduces mismatches at diagnostic primer/probe sites.
A multi‐target RT‐PCR/MALDI‐TOF assay captures emergent variants in NYC patients.
Paired sequencing data reveals the Alpha‐specific A28095T causes target dropout.
Diagnostic target performance illuminates dynamics of circulating SARS‐CoV‐2.
U.S. Marine Corps recruits quarantined at home for 2 weeks; after this period, 0.9% were found to be infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During a second, ...supervised 2-week quarantine on a college campus, 1.9% had become newly infected, and most were asymptomatic.
Influenza A viruses (IAVs) remain a significant public health threat, causing more than 300,000 hospitalizations in the United States during the 2015-2016 season alone. While only a few IAVs of avian ...origin have been associated with human infections, the ability of these viruses to cause zoonotic infections further increases the public health risk of influenza. Of these, H9N2 viruses in Asia are of particular importance as they have contributed internal gene segments to other emerging zoonotic IAVs. Notably, recent H9N2 viruses have acquired molecular markers that allow for a transition from avian-like to human-like terminal sialic acid (SA) receptor recognition via a single amino acid change at position 226 (H3 numbering), from glutamine (Q226) to leucine (L226), within the hemagglutinin (HA) receptor-binding site (RBS). We sought to determine the plasticity of amino acid 226 and the biological effects of alternative amino acids on variant viruses. We created a library of viruses with the potential of having any of the 20 amino acids at position 226 on a prototypic H9 HA subtype IAV. We isolated H9 viruses that carried naturally occurring amino acids, variants found in other subtypes, and variants not found in any subtype at position 226. Fitness studies in quails revealed that some natural amino acids conferred an
replication advantage. This study shows the flexibility of position 226 of the HA of H9 influenza viruses and the resulting effect of single amino acid changes on the phenotype of variants
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A single amino acid change at position 226 in the hemagglutinin (HA) from glutamine (Q) to leucine (L) has been shown to play a key role in receptor specificity switching in various influenza virus HA subtypes, including H9. We tested the flexibility of amino acid usage and determined the effects of such changes. The results reveal that amino acids other than L226 and Q226 are well tolerated and that some amino acids allow for the recognition of both avian and human influenza virus receptors in the absence of other changes. Our results can inform better avian influenza virus surveillance efforts as well as contribute to rational vaccine design and improve structural molecular dynamics algorithms.
Abstract
Gastrointestinal symptoms are common in COVID-19 patients but the nature of the gut immune response to SARS-CoV-2 remains poorly characterized, partly due to the difficulty of obtaining ...biopsy specimens from infected individuals. In lieu of tissue samples, we measured cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from a cohort of 44 hospitalized COVID-19 patients. SARS-CoV-2 RNA was detected in stool of 41% of patients and more frequently in patients with diarrhea. Patients who survived had lower fecal viral RNA than those who died. Strains isolated from stool and nasopharynx of an individual were the same. Compared to uninfected controls, COVID-19 patients had higher fecal levels of IL-8 and lower levels of fecal IL-10. Stool IL-23 was higher in patients with more severe COVID-19 disease, and we found evidence of intestinal virus-specific IgA responses associated with more severe disease. We provide evidence for an ongoing humeral immune response to SARS-CoV-2 in the gastrointestinal tract, but little evidence of overt inflammation.
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