SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

EBioMedicine, Год журнала: 2022, Номер 84, С. 104270 - 104270

Опубликована: Сен. 18, 2022

BackgroundGenetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. The introduction global vaccine programs has contributed to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, Omicron BA.1 emerged, with substantially altered genetic differences clinical effects from other concern. Shortly after dominating spread early 2022, was supplanted by the genetically lineage BA.2. A sub-lineage BA.2, designated BA.5, presently an outgrowth advantage over BA.2 sub-lineages. Here we study neutralisation BA.1, BA.5 pre-Omicron using a range convalescent sera therapeutic monoclonal antibodies live virus assay. Using primary nasopharyngeal swabs, also tested relative fitness compared lineages their ability use ACE2-TMPRSS2 pathway.MethodsUsing low passage isolates Clade A.2.2, Beta, Delta, determined humoral vitro vaccinated cohorts, concentrated human IgG pooled thousands plasma donors, licensed antibody therapies. We then infectivity particle ratios samples expanded engineered ACE2/TMPRSS2 cell line presence absence TMPRSS2 inhibitor Nafamostat.FindingsPeak responses 3 doses BNT162b2 were associated 9-fold reduction for BA.5. Concentrated donors vaccination breakthrough infections greater breadth neutralisation, although potency still reduced 7-fold across all lineages. Testing grade revealed 14.3-fold Evusheld 16.8-fold Sotrovimab Whilst attenuated entry, observed be equivalent that 2020 circulating clade had sensitivity Nafamostat.InterpretationObservations support significantly escape neutralising and/or responses. Potency is differs key difference sub-variants reversion tropism back well-known pathway, utilised efficiently Monitoring if these changes influence transmission disease severity will ongoing tracking management waves globally.FundingThis work primarily supported Australian Medical Foundation research grants MRF2005760 (ST, GM & WDR), MRF2001684 (ADK ST) Research Future Fund Antiviral Development Call grant (WDR), (MRFF2001684, ADK SGT) New South Wales Health Grants Round (SGT).

Язык: Английский

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The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses

Nature reviews. Immunology, Год журнала: 2022, Номер 23(5), С. 304 - 316

Опубликована: Дек. 20, 2022

Язык: Английский

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Short-term effectiveness of the XBB.1.5 updated COVID-19 vaccine against hospitalisation in Denmark: a national cohort study

The Lancet Infectious Diseases, Год журнала: 2024, Номер 24(2), С. e73 - e74

Опубликована: Янв. 5, 2024

Язык: Английский

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Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Viruses, Год журнала: 2023, Номер 15(1), С. 175 - 175

Опубликована: Янв. 7, 2023

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease death. Understanding the risk factors is relevant both in setting at epidemiological level. Here, we provide an overview host, viral environmental that have been shown or (in some cases) hypothesized be associated with outcomes. considered detail include age frailty, genetic polymorphisms, biological sex (and pregnancy), co- superinfections, non-communicable comorbidities, immunological history, microbiota, lifestyle patient; variation infecting dose; socioeconomic factors; air pollution. For each category, compile (sometimes conflicting) evidence for association factor outcomes (including strength effect) outline possible action mechanisms. We also discuss complex interactions between various factors.

Язык: Английский

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Protective immunity of SARS-CoV-2 infection and vaccines against medically attended symptomatic omicron BA.4, BA.5, and XBB reinfections in Singapore: a national cohort study

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(7), С. 799 - 805

Опубликована: Март 13, 2023

Язык: Английский

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SARS‐CoV‐2 in animals: susceptibility of animal species, risk for animal and public health, monitoring, prevention and control

EFSA Journal, Год журнала: 2023, Номер 21(2)

Опубликована: Фев. 1, 2023

Abstract The epidemiological situation of SARS-CoV-2 in humans and animals is continually evolving. To date, animal species known to transmit are American mink, raccoon dog, cat, ferret, hamster, house mouse, Egyptian fruit bat, deer mouse white-tailed deer. Among farmed animals, mink have the highest likelihood become infected from or further SARS-CoV-2. In EU, 44 outbreaks were reported 2021 farms seven MSs, while only six 2022 two thus representing a decreasing trend. introduction into usually via humans; this can be controlled by systematically testing people entering adequate biosecurity. current most appropriate monitoring approach for outbreak confirmation based on suspicion, dead clinically sick case increased mortality positive farm personnel genomic surveillance virus variants. analysis showed mink-specific clusters with potential spill back human population. companion cats, ferrets hamsters those at risk infection, which likely originates an human, has no very low impact circulation wild (including zoo animals), mostly carnivores, great apes been naturally cases wildlife so far. Proper disposal waste advised reduce risks spill-over wildlife. Furthermore, contact wildlife, especially if dead, should minimised. No specific recommended apart hunter-harvested clinical signs found-dead. Bats monitored as natural host many coronaviruses.

Язык: Английский

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Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population level

EBioMedicine, Год журнала: 2023, Номер 90, С. 104545 - 104545

Опубликована: Март 30, 2023

Язык: Английский

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Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants

Nature Microbiology, Год журнала: 2024, Номер 9(2), С. 451 - 463

Опубликована: Янв. 16, 2024

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve globally dominant subvariants. Here we compared their replication cell lines and primary airway cultures measured host responses infection. We discovered that subvariants BA.4 BA.5 have improved suppression innate immunity when earlier BA.1 BA.2. Similarly, more recent (BA.2.75 XBB lineages) also triggered reduced immune activation. This correlated increased expression viral antagonists Orf6 nucleocapsid, reminiscent VOCs Alpha Delta. Increased levels suppressed infection by decreasing IRF3 STAT1 signalling transcription factor phosphorylation nuclear translocation. Our data suggest convergent evolution antagonist a common pathway link subvariant dominance evasion.

Язык: Английский

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Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without omicron breakthrough infection

Med, Год журнала: 2022, Номер 3(12), С. 838 - 847.e3

Опубликована: Окт. 5, 2022

Язык: Английский

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The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5

EBioMedicine, Год журнала: 2023, Номер 95, С. 104753 - 104753

Опубликована: Авг. 12, 2023

Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related resulted in largest number of infections. While recent studies demonstrated all robustly escape neutralizing antibody response, it remains unclear on whether these share any pattern evolutionary trajectory replication efficiency intrinsic pathogenicity along respiratory tract.We compared virological features, capacity dominant BA.2 BA.5 human nasal epithelium, characterized K18-hACE2, A129, young C57BL/6, aged C57BL/6 mice.We found replicated most robustly, followed by differentiated epithelium. Consistently, infection higher viral gene copies, infectious titres more abundant antigen expression turbinates infected K18-hACE2 transgenic mice. In contrast, are continuously attenuated lungs mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe sublineages-infected A129 mice.Our results suggested might be gaining fitness upper tract, therefore highlighting importance global surveillance emergence hyper-transmissive sublineages. On contrary, is further lower tract. Effective vaccination other precautions should place prevent infections immunocompromised populations at risk.A full list funding bodies contributed this study can Acknowledgements section.

Язык: Английский

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