tetano
Editor, Senior Moderator
J Clin Immunol
. 2021 Oct 30.
doi: 10.1007/s10875-021-01142-z. Online ahead of print.
Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection
Siew-Wai Fong[SUP] #[/SUP][SUP] 1 [/SUP], Nicholas Kim-Wah Yeo[SUP] #[/SUP][SUP] 1 [/SUP], Yi-Hao Chan[SUP] 1 [/SUP], Yun Shan Goh[SUP] 1 [/SUP], Siti Naqiah Amrun[SUP] 1 [/SUP], Nicholas Ang[SUP] 2 [/SUP], Menaka Priyadharsani Rajapakse[SUP] 2 [/SUP], Josephine Lum[SUP] 2 [/SUP], Shihui Foo[SUP] 2 [/SUP], Cheryl Yi-Pin Lee[SUP] 1 [/SUP], Guillaume Carissimo[SUP] 1 [/SUP], Rhonda Sin-Ling Chee[SUP] 1 [/SUP], Anthony Torres-Ruesta[SUP] 1 3 [/SUP], Matthew Zirui Tay[SUP] 1 [/SUP], Zi Wei Chang[SUP] 1 [/SUP], Chek Meng Poh[SUP] 1 [/SUP], Barnaby Edward Young[SUP] 4 5 6 [/SUP], Paul A Tambyah[SUP] 4 7 8 [/SUP], Shirin Kalimuddin[SUP] 9 10 [/SUP], Yee-Sin Leo[SUP] 4 5 6 11 [/SUP], David C Lye[SUP] 4 5 6 11 [/SUP], Bernett Lee[SUP] 2 [/SUP], Subhra Biswas[SUP] 2 [/SUP], Shanshan Wu Howland[SUP] 2 [/SUP], Laurent Renia[SUP] 1 2 [/SUP], Lisa F P Ng[SUP] 12 13 14 15 [/SUP]
Affiliations
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.
Keywords: Adaptive immune response; Antibody response; CD4+ T cell response; CD8+ T cell response; COVID-19; ORF8; SARS-CoV-2; Transcriptome.
. 2021 Oct 30.
doi: 10.1007/s10875-021-01142-z. Online ahead of print.
Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection
Siew-Wai Fong[SUP] #[/SUP][SUP] 1 [/SUP], Nicholas Kim-Wah Yeo[SUP] #[/SUP][SUP] 1 [/SUP], Yi-Hao Chan[SUP] 1 [/SUP], Yun Shan Goh[SUP] 1 [/SUP], Siti Naqiah Amrun[SUP] 1 [/SUP], Nicholas Ang[SUP] 2 [/SUP], Menaka Priyadharsani Rajapakse[SUP] 2 [/SUP], Josephine Lum[SUP] 2 [/SUP], Shihui Foo[SUP] 2 [/SUP], Cheryl Yi-Pin Lee[SUP] 1 [/SUP], Guillaume Carissimo[SUP] 1 [/SUP], Rhonda Sin-Ling Chee[SUP] 1 [/SUP], Anthony Torres-Ruesta[SUP] 1 3 [/SUP], Matthew Zirui Tay[SUP] 1 [/SUP], Zi Wei Chang[SUP] 1 [/SUP], Chek Meng Poh[SUP] 1 [/SUP], Barnaby Edward Young[SUP] 4 5 6 [/SUP], Paul A Tambyah[SUP] 4 7 8 [/SUP], Shirin Kalimuddin[SUP] 9 10 [/SUP], Yee-Sin Leo[SUP] 4 5 6 11 [/SUP], David C Lye[SUP] 4 5 6 11 [/SUP], Bernett Lee[SUP] 2 [/SUP], Subhra Biswas[SUP] 2 [/SUP], Shanshan Wu Howland[SUP] 2 [/SUP], Laurent Renia[SUP] 1 2 [/SUP], Lisa F P Ng[SUP] 12 13 14 15 [/SUP]
Affiliations
- PMID: 34716845
- DOI: 10.1007/s10875-021-01142-z
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.
Keywords: Adaptive immune response; Antibody response; CD4+ T cell response; CD8+ T cell response; COVID-19; ORF8; SARS-CoV-2; Transcriptome.