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

• DOI: 10.1007/s10875-021-01142-z
• Publication Date: 2021-10-30T14:02:52Z
• Authors: Siew-Wai Fong; Nicholas Kim-Wah Yeo; Yi-Hao Chan; Yun Shan Goh; Siti Naqiah Amrun; Nicholas Ang; Menaka Priyadhars...; Josephine Lum; Shihui Foo; Cheryl Yi-Pin Lee; Guillaume Carissimo; Rhonda Sin-Ling Chee; Anthony Torres-Ru...; Matthew Zirui Tay; Zi Wei Chang; Chek Meng Poh; Barnaby Edward Young; Paul A. Tambyah; Shirin Kalimuddin; Yee-Sin Leo; David C. Lye; Bernett Lee; Subhra Biswas; Shanshan Wu Howland; Laurent Renia; Lisa F. P. Ng
• Keywords: Inflammation; 0303 health sciences; SARS-CoV-2; T-Lymphocytes; COVID-19; Adaptive Immunity; 3. Good health; 03 medical and health sciences; Host-Pathogen Interactions; Mutation; Cytokines; Humans; Original Article; Pandemics

AbstractThe 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.