Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection

Abstract

In response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.

Keywords: COVID-19; Immune Response; Multi-omics; Pathogenesis; SARS-CoV-2; Virology.

Fig. 1. Multiomic technologies facilitate the determination of the virological and immunological characteristics of SARS-CoV-2 infection, the discovery of biomarkers, and the elucidation of COVID-19 pathogenesis.

With the use of genomic and transcriptomic-based sequencing, virological characteristics, including the genome, transcriptome, and virus-host interactions of SARS-CoV-2, have been elucidated. Moreover, the characteristics of the immune responses and the pathogenesis of COVID-19, especially in association with severe disease, have been extensively characterized. Systemic and tissue-specific immune disorders, such as lymphopenia, cytokine storm, emergency myelopoiesis, peripheral immune paralysis, and lung inflammation, are strongly associated with the manifestations of severe/critical COVID-19, including acute respiratory distress syndrome, coagulation disorders, and lung fibrosis.

Fig. 2. Immune dysfunction of the lung and peripheral compartments in mild and severe COVID-19.

Using scRNA-seq and mass cytometry, lung and peripheral immune responses have been examined in patients with mild and severe COVID-19. In the peripheral blood of patients with severe COVID-19, immature/dysfunctional myeloid cells (e.g., HLA-DR^loCD163^hiCD14⁺ monocytes, HLA-DR^loS100A^hiCD14⁺ monocytes, and CD10^loCD101^-CXCR4^+/– immature/dysfunctional neutrophils), GzB⁺ MAIT cells, CD56⁺CD69⁺MAIT cells, and hyperinflammatory megakaryocytes accumulated, while nonclassical monocytes (CD14^loCD16^hi) and total MAIT cells are depleted. Recruitment of immature/dysfunctional myeloid cells and peripheral T cells to pulmonary sites further promotes the cytokine storm and the inflammatory environment during severe COVID-19. In contrast, mild cases tend to have well-controlled immune homeostasis, including the appropriate activation of myeloid cells, T cells, and antiviral signaling as well as clonal expansion of resident T cells in lung tissues.

Fig. 3. Remaining questions regarding immunity related to COVID-19.

There are many unresolved immunological questions regarding the pathogenesis and complications related to COVID-19. Of note, little is understood about protective immunity in asymptomatic patients, key early factors associated with disease severity, risk factors that affect COVID-19 outcomes, immune responses associated with SARS-CoV-2 reinfection, and long-term immune memory in convalescent COVID-19.