In June 2023, a multicenter study led by Professor Tao Cheng  and his team at the Blood Disease Hospital of the Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) was published in the top international academic journal "Immunity" (IF=43.474). The title of the research is "Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection." The study indicates that during the Omicron breakthrough infection, platelets exhibit enhanced immune features and reduced thrombus formation. This advancement contributes to a better understanding of the dynamic host response to Omicron and holds potential clinical significance. The study was also recently selected as one of the "Top 10 Advances in Chinese Hematology Research in 2023."

The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people worldwide. The emergence of new variants, such as Omicron, has raised concerns about the effectiveness of immune responses and the severity of the disease. In this study, we aimed to characterize the immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection using a multi-omics approach.

We collected over 1,000 blood and plasma samples from patients with Omicron breakthrough infection. We employed multi-omics analysis, including clinical phenomes, plasma proteomics, plasma metabolomics, platelet proteomics, platelet transcriptomics, and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs). The data were analyzed using statistical methods and bioinformatics tools to identify key features and pathways.

Our findings revealed several unique features of the immune and platelet responses to Omicron infection. We observed imbalanced responses across the stages of infection, with platelets exhibiting enhanced interferon-mediated antiviral features. Platelet-leukocyte aggregates were found to modulate immune cell functions, suggesting a role for platelets in immune regulation during Omicron breakthrough infection.

Furthermore, patients who were re-tested positive for viral RNA showed reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. This indicates a potential waning of immunity over time and the need for booster vaccinations in Omicron-infected individuals.

Intriguingly, our multi-omics data also allowed us to develop a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. This predictive tool has the potential to aid healthcare professionals in identifying individuals at higher risk of reinfection and tailoring their treatment plans accordingly.

The multi-omics analysis provided a comprehensive view of the molecular and cellular landscapes in the blood of Omicron-infected patients. The enhanced immune signatures and reduced thrombosis observed in platelets indicate a distinct immune landscape during Omicron breakthrough infection.

These findings not only advance our understanding of the host response dynamics to Omicron but also have potential clinical implications. Developing strategies to enhance immune responses, such as personalized booster vaccinations, could be crucial in managing breakthrough infections. Moreover, the role of platelets in modulating immune responses warrants further investigation, as it may offer novel therapeutic targets.

Our study characterized the unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection using a multi-omics approach. The findings provide valuable insights into the host response dynamics and the development of screening and treatment strategies for Omicron breakthrough infection.

In summary, the multi-omics blood atlas study sheds light on the distinct features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection. The findings contribute to our understanding of the disease dynamics and may help guide future therapeutic approaches. As the pandemic continues to evolve, a multidisciplinary approach is crucial to staying ahead of emerging variants and developing effective strategies to combat them.