Innate immune imprints in SARS-CoV-2 Omicron variant infection convalescents

SARS-CoV-2 Omicron variant infection generally gives rise to asymptomatic to moderate COVID-19 in vaccinated people. The immune cells can be reprogrammed or imprinted by vaccination and infections to generate protective immunity against subsequent challenges. Considering the immune imprint in Omicron infection is unclear, here we delineate the innate immune landscape of human Omicron infection via single-cell RNA sequencing, surface proteome profiling, and plasma cytokine quantification. We found that monocyte responses predominated in immune imprints of Omicron convalescents, with IL-1 beta-associated and interferon (IFN)-responsive signatures with mild and moderate symptoms, respectively. Low-density neutrophils increased and exhibited IL-1 beta-associated and IFN-responsive signatures similarly. Mild convalescents had increased blood IL-1 beta, CCL4, IL-9 levels and PI3(+) neutrophils, indicating a bias to IL-1 beta responsiveness, while moderate convalescents had increased blood CXCL10 and IFN-responsive monocytes, suggesting durative IFN responses. Therefore, IL-1 beta- or IFN-responsiveness of myeloid cells may indicate the disease severity of Omicron infection and mediate post-COVID conditions.

Automated summary

This study investigates the innate immune landscape of human Omicron infection and finds that IL-1 beta or IFN responsiveness of myeloid cells may indicate the severity of the disease. This information could help understand the immune response to Omicron variant and its impact on COVID-19 outcomes.