Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection
Siew‐Wai Fong, Nicholas Kim‐Wah Yeo, Yi‐Hao Chan, Yun Shan Goh, Siti Naqiah Amrun, Nicholas Ang, Menaka Priyadharsani Rajapakse, Josephine Lum, Shihui Foo, Cheryl Yi‐Pin Lee, Guillaume Carissimo, Rhonda Sin‐Ling Chee, Anthony Torres‐Ruesta, Matthew Zirui Tay, Zi Wei Chang, Chek Meng Poh, Barnaby Edward Young, Paul Anantharajah Tambyah, Shirin Kalimuddin, Yee‐Sin Leo, David Chien Lye, Bernett Lee, Subhra K. Biswas, Shanshan Wu Howland, Laurent Rénia, Lisa F. P. Ng
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.