Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection



Fong, Siew-Wai, Yeo, Nicholas Kim-Wah, Chan, Yi-Hao, Goh, Yun Shan, Amrun, Siti Naqiah, Ang, Nicholas, Rajapakse, Menaka Priyadharsani, Lum, Josephine, Foo, Shihui, Lee, Cheryl Yi-Pin
et al (show 16 more authors) (2022) Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection. JOURNAL OF CLINICAL IMMUNOLOGY, 42 (2). pp. 214-229.

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Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host-pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.

Item Type: Article
Uncontrolled Keywords: COVID-19, SARS-CoV-2, Transcriptome, ORF8, Adaptive immune response, CD4(+) T cell response, CD8(+) T cell response, Antibody response
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 01 Feb 2022 10:44
Last Modified: 18 Oct 2023 01:15
DOI: 10.1007/s10875-021-01142-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3147945