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. 2025 Mar 28;22(1):89.
doi: 10.1186/s12985-025-02696-9.

Identification of aberrant interferon-stimulated gene associated host responses potentially linked to poor prognosis in COVID-19 during the Omicron wave

Affiliations

Identification of aberrant interferon-stimulated gene associated host responses potentially linked to poor prognosis in COVID-19 during the Omicron wave

Zhan Li et al. Virol J. .

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron has demonstrated decreased pathogenicity, yet a few individuals suffer severe pneumonia from coronavirus disease 2019 (COVID-19) infection; the underlying mechanisms are unknown.

Methods: The present work investigated the role of Interferon-stimulated genes (ISGs) in the occurrence and progression of severe Omicron infection. The expression and dynamic changes of ISGs were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), and the anti-ISG15 autoantibody in infected patients was detected by ELISA. Moreover, we evaluated the correlation of ISGs with disease severity and outcomes by comparing expression of ISGs among each group.

Results: Decreased expression of several ISGs such as IFI6 are potentially linked to increased severity or poor outcomes of Omicron infection. Longitudinal data also demonstrates that the dynamic variation of IFI6 in the Omicron infection phase may be linked to the prognosis of the disease. The increase of anti-ISG15 autoantibody potentially links to the disease progression and poor outcome of patients with high level of ISG15 expression.

Conclusions: These findings define aberrant Interferon-stimulated gene associated host responses and reveal potential mechanisms and therapeutic targets for Omicron or other viral infection.

Keywords: Antiviral restriction factors; COVID-19; ISG; Interferons; SARS-CoV-2 Omicron variant.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013), was approved by the Institutional Review Committee of Peking Union Medical College Hospital (approval number: I-23PJ292). Written informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study design
Fig. 2
Fig. 2
The comparison of lymphocytes, hsCRP, D-Dimer, and ferritin in the peripheral blood among cases with different severity of Omicron infection (mild and moderate, severe, and critically severe patients, A-D) and between the survival group and mortality group (E-H). P-values were determined by Kruskal-Wallis test (A-D) and Mann-Whitney test (E-H). All comparisons unreported had p-values greater than 0.05. M/M: mild and moderate
Fig. 3
Fig. 3
The comparison of ISG mRNA expression in the peripheral blood among cases with different severity of Omicron infection (mild and moderate, severe, and critically severe patients) and healthy controls. P-values were determined by Kruskal-Wallis test. All comparisons unreported had p-values greater than 0.05. HC: healthy control
Fig. 4
Fig. 4
The comparison of ISG mRNA expression in the peripheral blood among cases with different outcomes of Omicron infection (survival and dead patients) and healthy controls. P-values were determined by Kruskal-Wallis test. All comparisons unreported had p-values greater than 0.05
Fig. 5
Fig. 5
Dynamic variation of IFI6, IFITM1, ISG15, and SIGLEC1 mRNA expression across three sampling timepoints in patients who survived or died during the entire phase of Omicron infection. The x-axis shows the three timepoints. The y-axis represents 2^-△△Ct. T, timepoint
Fig. 6
Fig. 6
The comparison of anti-ISG15 autoantibody in the plasma in cases with different outcome of Omicron infection. P-value was determined by Kruskal-Wallis test (p > 0.05)

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