Comparison of SARS-CoV-2 variants of concern in primary human nasal cultures demonstrates Delta as most cytopathic and Omicron as fastest replicating

mBio, Journal Year: 2024, Volume and Issue: 15(4)

Published: March 13, 2024

ABSTRACT The SARS-CoV-2 pandemic was marked with emerging viral variants, some of which were designated as variants concern (VOCs) due to selection and rapid circulation in the human population. Here, we elucidate functional features each VOC linked variations replication rate. Patient-derived primary nasal cultures grown at air-liquid interface used model upper respiratory infection compared cell lines derived from lung epithelia. All VOCs replicated higher titers than ancestral virus, suggesting a for efficiency. In cultures, Omicron highest early time points, followed by Delta, paralleling comparative studies population sampling. viruses entered primarily via transmembrane serine protease 2 (TMPRSS2)-dependent pathway, more likely use an endosomal route entry. activated overcame dsRNA-induced cellular responses, including interferon (IFN) signaling, oligoadenylate ribonuclease L degradation, protein kinase R activation. Among VOCs, induced expression most IFN IFN-stimulated genes. Infections resulted damage, compromise barrier integrity loss cilia ciliary beating function, especially during Delta infection. Overall, optimized tract least favorable lower line, cytopathic both cells. Our findings highlight differences among level imply distinct mechanisms pathogenesis infected individuals. IMPORTANCE Comparative analysis infections virus concern, Alpha, Beta, Omicron, indicated that selected efficiency replication. patient-derived infection, reached finding confirmed parallel sampling studies. While all dsRNA-mediated host strongest interferon-stimulated gene response. damaging cells syncytia formation, integrity, function.

Language: Английский

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Replacement of the Gamma by the Delta variant in Brazil: Impact of lineage displacement on the ongoing pandemic

Virus Evolution, Journal Year: 2022, Volume and Issue: 8(1)

Published: Jan. 1, 2022

Abstract The coronavirus disease 2019 (COVID-19) epidemic in Brazil was driven mainly by the spread of Gamma (P.1), a locally emerged variant concern (VOC) that first detected early January 2021. This estimated to be responsible for more than 96 per cent cases reported between and June 2021, being associated with increased transmissibility severity, reduction neutralization antibodies effectiveness treatments or vaccines, diagnostic detection failure. Here we show that, following several importations predominantly from USA, Delta rapidly replaced after July However, contrast what seen other countries, rapid did not lead large increase number deaths Brazil. We suggest this likely due relatively successful vaccination campaign coupled natural immunity acquired prior infection Gamma. Our data reinforce reports and, considering increasing recently identified Omicron variant, argues necessity strengthen genomic monitoring on national level quickly detect emergence VOCs might threaten global health.

Language: Английский

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Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania

mBio, Journal Year: 2022, Volume and Issue: 13(5)

Published: Aug. 24, 2022

Coronaviruses have been documented to replicate in numerous species of vertebrates, and multiple spillovers coronaviruses from animals into humans founded human epidemics. The COVID-19 epidemic likely derived a spillover SARS-CoV-2 bats humans, possibly via an intermediate host.

Language: Английский

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Infections with the SARS-CoV-2 Delta variant exhibit fourfold increased viral loads in the upper airways compared to Alpha or non-variants of concern

Scientific Reports, Journal Year: 2022, Volume and Issue: 12(1)

Published: Aug. 17, 2022

Abstract There has been a growing body of evidence that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) shows enhanced transmissibility and increased viral loads compared to other variants. A recent study even suggested samples from people infected with can harbor up 1000 times higher variants are more closely related original Wuhan strain, although sample size this (n = 125) was very limited. Here, we have load in 16,185 were obtained periods during which non-VOC, Alpha (B.1.1.7) or dominant as evidenced by genomic surveillance. We found contained about fourfold across all age groups non-VOC variants, is significantly lower than reported earlier. Interestingly, for seemed be age-dependent, regardless sex, 14-fold group 0–20 years 21–40 years, while there no difference between 41–60 61+ most likely consequence degree vaccination older groups.

Language: Английский

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The alpha/B.1.1.7 SARS-CoV-2 variant exhibits significantly higher affinity for ACE-2 and requires lower inoculation doses to cause disease in K18-hACE2 mice

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Nov. 25, 2021

The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases many European countries. incidence domination likely due to a fitness advantage that could be driven by receptor-binding domain (RBD) residue change (N501Y), which also independently other variants of concern such as beta/B.1.351 gamma/P.1 strains. Here, we present functional characterization variant show an eightfold affinity increase towards human angiotensin-converting enzyme-2 (ACE-2). In accordance with this, transgenic hACE2 mice showed faster disease progression severity after infection low dose B.1.1.7, compared early isolate. When challenged sera from convalescent individuals or anti-RBD monoclonal antibodies, N501Y minor, but significant elevated evasion potential ACE-2/RBD antibody neutralization. data suggest single asparagine tyrosine substitution remarkable rise may higher transmission rate B.1.1.7 variant.

Language: Английский

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Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission

Biomaterials, Journal Year: 2022, Volume and Issue: 288, P. 121671 - 121671

Published: July 18, 2022

Because oral transmission of SARS-CoV-2 is 3-5 orders magnitude higher than nasal transmission, we investigated debulking viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, microbubble count (based on N-antigen) was significantly reduced by 20 μg FRIL (p < 0.0001) and 0.925 CTB-ACE2 = 0.0001). Among delta or NP 17 had virus load below detection level spike protein RAPID assay, after incubation with gum powder. A dose-dependent 50% plaque reduction 50-100 ng 600-800 against Influenza strains H1N1, H3N2, Coronavirus HCoV-OC43 observed both purified FRIL, lablab bean powder electron micrographs, large/densely packed clumps overlapping influenza particles were observed. Chewing simulator studies revealed that release time/dose-dependent linear up to min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) progress evaluate saliva before CTB-ACE2/placebo Collectively, this study advances concept deliver debulk decrease infection/transmission.

Language: Английский

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SARS-CoV-2 Delta Variant (AY.3) in the Feces of a Domestic Cat

Viruses, Journal Year: 2022, Volume and Issue: 14(2), P. 421 - 421

Published: Feb. 17, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have spilled over from humans to companion and wild animals since the inception of global COVID-19 pandemic. However, whole genome sequencing data viral genomes that infect non-human animal species been scant. Here, we detected sequenced a SARS-CoV-2 delta variant (AY.3) in fecal samples an 11-year-old domestic house cat previously exposed owner who tested positive for SARS-CoV-2. Molecular testing two collected 7 days apart yielded relatively high levels RNA. Sequencing feline-derived showed be identical, differing by between 4 14 single nucleotide polymorphisms pairwise comparisons human-derived lineage AY.3 sequences same geographic area time period. several mutations unique feline reveal their divergence this cohort on phylogenetic analysis. These results demonstrate continued spillover emerging variants threaten human health, as well highlight importance collecting when animals. To authors' knowledge, is first published case United States.

Language: Английский

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Investigating SARS-CoV-2 breakthrough infections per variant and vaccine type

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 24, 2022

Breakthrough SARS-CoV-2 infections have been reported in fully vaccinated individuals, spite of the high efficacy currently available vaccines, proven trials and real-world studies. Several variants concern (VOC) proffered to be associated with breakthrough following immunization. In this study, we investigated 378 recorded between January July 2021 compared distribution genotypes identified 225 individuals frequency circulating community lineages region South Limburg (The Netherlands) a week-by-week comparison. Although proportion was relatively low stable when Alpha variant predominant, rapid emergence Delta lead strong increase infections, higher relative Vaxzevria or Jcovden being infected those immunized mRNA-based vaccines. A significant difference median age observed comparing severe symptoms (83 years) asymptomatic cases (46.5 mild-to-moderate (42 years). There no association genotype vaccine type disease symptoms. Furthermore, majority adaptive mutations were concentrated N-terminal domain Spike protein, highlighting its role immune evasion. Interestingly, symptomatic harbored significantly loads than caused by increased viral variant. addition, Omicron causing analyzing 135 samples that randomly selected for genomic surveillance during transition period from Omicron. We found vs. who received booster both unvaccinated individuals. Altogether, these results indicate particular has lowered efficiency types prevent that, although rare, elderly are particularly at risk becoming severely as consequence infection.

Language: Английский

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Multiple Introductions of SARS-CoV-2 Alpha and Delta Variants into White-Tailed Deer in Pennsylvania

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Feb. 19, 2022

Introductory paragraph The SARS-CoV-2 pandemic likely began by viral spillover from animals to humans 1-3 ; today multiple animal species are known be susceptible infection 4-8 . White-tailed deer, Odocoileus virginianus infected in North America at substantial levels 9-11 , and genomic data suggests that a variant deer may have spilled back 12,13 Here we characterize Pennsylvania (PA) sampled during fall winter 2021. Of 123 nasal swab samples analyzed RT-qPCR, 20 (16.3%) were positive for SARS-CoV-2. Seven whole-genome sequences obtained, together with six more partial spike sequences. These annotated as alpha delta variants, the first reported observations of these lineages documenting new jumps deer. lineage persisted after its displacement humans, deer-derived variants diverged significantly those consistent distinctive evolutionary trajectory

Language: Английский

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Real-world effectiveness of casirivimab and imdevimab among patients diagnosed with COVID-19 in the ambulatory setting: a retrospective cohort study using a large claims database

BMJ Open, Journal Year: 2022, Volume and Issue: 12(12), P. e064953 - e064953

Published: Dec. 1, 2022

To assess the real-world effectiveness of casirivimab and imdevimab (CAS+IMD) versus no COVID-19 antibody treatment among patients diagnosed with in ambulatory setting, including during Delta-dominant period prior to Omicron emergence.

Language: Английский

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