Multi-omics blood atlas reveals unique features of immune and platelet responses to SARS-CoV-2 Omicron breakthrough infection

Immunity. 2023 Jun 13;56(6):1410-1428.e8. doi: 10.1016/j.immuni.2023.05.007. Epub 2023 May 16.


Although host responses to the ancestral SARS-CoV-2 strain are well described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron-infected patients, and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were re-tested positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation, and neutralizing capacity against Omicron. Finally, we developed a machine learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift in studying systemic diseases and emerging public health concerns.

Keywords: COVID-19; Omicron, platelet; blood; metabolome; plasma; platelet-leukocyte aggregate; proteome; re-positive; single-cell RNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Blood Platelets*
  • Breakthrough Infections
  • COVID-19*
  • Humans
  • Multiomics
  • SARS-CoV-2


  • Antibodies, Neutralizing
  • Antibodies, Viral

Supplementary concepts

  • COVID-19 breakthrough infections
  • SARS-CoV-2 variants