Dataset Information

Attenuated pathogenicity coupled with novel features of SARS-CoV-2 Omicron BA.2.75 and BA.5 variants

ABSTRACT: The Coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global threat, exacerbated by the emergence of viral variants. Two recent variants of SARS-CoV-2, Omicron BA.2.75 and BA.5, have been reported globally, yet their precise characteristics are not well understood. In this study, we compared these two Omicron sub-lineages with the previously dominant Delta variant using a hACE2 knock-in mouse model. As expected, Delta exhibited higher viral replication in the lung and brain than both Omicron sub-lineages that induced less severe lung damage and immune activation. In contrast, the Omicron variants especially BA.5 showed a propensity for cellular proliferation and developmental pathways. Both Delta and BA.5 variants, but not BA.2.75, led to decreased pulmonary lymphocytes, indicating differential adaptive immune response. Neuroinvasiveness was shared with all strains, accompanied by vascular abnormalities, synaptic injury, and loss of astrocytes. However, Immunostaining assays and transcriptomic analysis showed that BA.5 displayed stronger immune suppression and neurodegeneration, while BA.2.75 exhibited more similar characteristics to Delta in the cortex. Such differentially infectious features could be partially attributed to the weakened interaction between Omicron Spike protein and host proteomes decoded via co-immunoprecipitation followed by mass spectrometry in neuronal cells. Our present study supports attenuated replication and pathogenicity of Omicron variants but also highlights their newly infectious characteristics in the lung and brain, especially with BA.5 demonstrating enhanced immune evasion and neural damage that could exacerbate neurological sequelae.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jianxiong Zeng

PROVIDER: PXD042841 | iProX | Fri Jun 09 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Similar Datasets

Project description:Background Omicron subvariants have led to millions of coronavirus disease 2019 (COVID-19) cases worldwide. Although Omicron breakthrough infections (BTIs) exhibit lower hospitalization rates than previous variants, post-COVID conditions persist. However, the immune response dynamics, lymphocyte subsets, and immune repertoire features following BA.5 sublineage BTI remain poorly understood. Methods In a longitudinal cohort, we monitored the recovery dynamics in patients with BTI at various time points. We employed single-cell transcriptomics, T cell receptor (TCR)/BCR sequencing, and antibody mass spectrometry to sequentially assess the immune response following BA.5.2 or BF.7 BTI. Findings Serological analysis revealed active cellular and humoral immunity 2 weeks post-BTI, with significant increases in cytokines (CKs) like IFN-γ, TNFβ, IL-2, and neutralizing antibodies. CK levels reverted to pre-infection levels, while broadly neutralizing antibodies remained high 1 month post-infection. Single-cell sequencing demonstrated robust immune activation and antiviral responses in NK, T, and B lymphocytes within 1 month post-BTI. Interestingly, the immune system maintained its strength to combat viral infection at 2 weeks post-BTI, transitioning toward repair and tissue damage elimination at 1 month. TCR/BCR library analysis revealed a higher clonal type in the BTI_2w group, mainly in NKT, memory T or B, and plasma cells, crucial for immune memory and antigen clearance. The BTI_1m group exhibited more IgG and IgA BCR subtypes, with somatic hypermutation indicating mature antibodies. Biological function verification of IgG and IgA-type monoclonal antibodies corresponding to expanded BCRs revealed antigen-specific and broad-spectrum antibodies. Interpretation Our study elucidated the dynamic immune profiling of individuals 2 weeks and 1 month after Omicron BA.5 sublineage BTI. This provided essential insights into pathogenicity, sequential immune status, recovery mechanisms of Omicron subvariant BTI, and novel concepts for broad-spectrum antibody development.

Dataset Information

Attenuated pathogenicity coupled with novel features of SARS-CoV-2 Omicron BA.2.75 and BA.5 variants

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets