Omicron: increased transmissibility and decreased pathogenicity

Balint, G. A.; Horváth, Barbara; Széchenyi, Aleksandar

doi:10.1038/s41392-022-01009-8

Cited by 129 publications

(125 citation statements)

References 5 publications

(24 reference statements)

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“…In contrast, the small changes in the RBD of BA.5 appear to encourage furin cleavage in recent studies using pseudotyped viral platforms 15 . This is consistent with observations for more efficient TMPRSS2 use, both herein and in animal models observing increased infection of the lung, in addition to increased disease severity 16 . Curiously, the change in BA.5 not only gives the virus greater antibody evasion potential but concurrently has changed its tropism along with an increased transmission potential in the community.…”

Section: Shifting Tropism Of the Ba5 Omicron Variantsupporting

confidence: 92%

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

Aggarwal

Akerman

Milogiannakis

et al. 2022

Preprint

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Genetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. Over this time global vaccine programs have been introduced, contributing to lowered COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, the Omicron BA.1 variant emerged, with significant genetic differences and clinical effects from other variants of concern (VOC). This variant demonstrated higher numbers of polymorphisms in the gene encoding the Spike (S) protein, and there has been displacement of the dominant Delta variant. Shortly after dominating global spread in early 2022, BA.1 was supplanted by the genetically distinct Omicron lineage BA.2. A sub-lineage of BA.2, designated BA.5 has now started to dominate globally, with the potential to supplant BA.2. To address the relative threat of BA.5, we determined infectivity to particle ratios in primary nasopharyngeal samples and expanded low passage isolates in a well characterised, genetically engineered ACE2/TMPRSS2 cell line. We then assessed the impact of BA.5 infection on humoral neutralisation in vitro, in vaccinated and convalescent cohorts, using concentrated human IgG pooled from thousands of plasma donors, and licensed monoclonal antibody therapies. The infectivity of virus in primary swabs and expanded isolates revealed whilst BA.1 and BA.2 are attenuated through ACE2/TMPRSS2, BA.5 infectivity is equivalent to that of an early 2020 circulating clade and has greater sensitivity to the TMPRSS2 inhibitor Nafamostat. As with BA.1, we observed BA.5 to significantly reduce neutralisation titres across all donors. Concentrated pooled human IgG from convalescent and vaccinated donors had greater breadth of neutralisation, although the potency was still reduced 7-fold with BA.5. Of all therapeutic antibodies tested, we observed a 14.3-fold reduction using Evusheld and 16.8 reduction using Sotrovimab when neutralising a Clade A versus BA.5 isolate. These results have implications for ongoing tracking and management of Omicron waves globally.

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Section: Shifting Tropism Of the Ba5 Omicron Variantsupporting

confidence: 92%

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

Aggarwal

Akerman

Milogiannakis

et al. 2022

Preprint

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“… 36 This is consistent with observations for more efficient TMPRSS2 use, both herein and in animal models observing increased infection of the lung and increased disease severity. 37 Curiously, a pre-print by Uraki and colleagues demonstrates that the other BA.2 sub-lineage BA.2.75 also appears to be taking a similar phenotypic trajectory to that of BA.5 (pre-print). 20 The change in BA.5 provides the virus greater antibody evasion potential, changed its tropism and increased transmission potential in the community.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“…Moreover, the transmissibility of Omicron is higher than its predecessors; this is mainly attributed to the high number of mutations in the spike protein [12, 41]. The high number of mutations contributed to 3-fold higher binding affinity of the RBD of Omicron to the ACE2 receptor compared to Wuhan HU-1 and Delta [42, 43]. Studies also showed that vaccine effectiveness against Omicron variant was lower than that of Delta and that neutralizing antibody activity against Omicron is significantly lower than Beta and Delta variants [17, 23, 44].…”

Section: Discussionmentioning

confidence: 99%

Genomic Surveillance of SARS CoV2 in COVID-19 vaccinated healthcare workers in Lebanon

Kalamouni

Hassan

Hamdan

et al. 2022

Preprint

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The emergence of SARS-CoV-2 variants including the Delta and Omicron along with waning of vaccine-induced immunity over time contributed to increased rates of breakthrough infection specifically among healthcare workers (HCWs). SARS-CoV-2 genomic surveillance is an important tool for timely detection and characterization of circulating variants as well as monitoring the emergence of new strains. Our study is the first national SARS-CoV-2 genomic surveillance among HCWs in Lebanon. We collected 250 samples from five hospitals across Lebanon between December 2021 and January 2022. We extracted viral RNA and performed whole genome sequencing using the Illumina NextSeq 500 platform. A total of 133 (57.1%) samples belonging to the Omicron (BA.1.1) sub-lineage were identified, as well as 44 (18.9%) samples belonging to the BA.1 sub-lineage, 28 (12%) belonging to the BA.2 sub-lineage, and only 15 (6.6%) samples belonging to the Delta variant sub-lineage B.1.617.2. These results show that Lebanon followed the global trend in terms of circulating SARS-CoV-2 variants with Delta rapidly replaced by the Omicron variant. This study underscores the importance of continuous genomic surveillance programs in Lebanon for the timely detection and characterization of circulating variants. The latter is critical to guide public health policy making and to timely implement public health interventions.

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Omicron: increased transmissibility and decreased pathogenicity

Cited by 129 publications

References 5 publications

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

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

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

Genomic Surveillance of SARS CoV2 in COVID-19 vaccinated healthcare workers in Lebanon

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