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Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19

Frontiers in Immunology, 2024

Baranova A., Luo J., Fu L., Yao G., Zhang F.

Disease areaApplication areaSample typeProducts
Infectious Diseases
Pathophysiology
Plasma
Olink Target 96

Olink Target 96

Abstract

Objective

The relationships between circulating inflammatory proteins and COVID-19 have been observed in previous cohorts. However, it is not unclear which circulating inflammatory proteins may boost the risk of or protect against COVID-19.

Methods

We performed Mendelian randomization (MR) analysis using GWAS summary result of 91 circulating inflammation-related proteins (N = 14,824) to assess their causal impact on severe COVID-19. The COVID-19 phenotypes encompassed both hospitalized (N = 2,095,324) and critical COVID-19 (N = 1,086,211). Moreover, sensitivity analyses were conducted to evaluate the robustness and reliability.

Results

We found that seven circulating inflammatory proteins confer positive causal effects on severe COVID-19. Among them, serum levels of IL-10RB, FGF-19, and CCL-2 positively contributed to both hospitalized and critical COVID-19 conditions (OR: 1.10~1.16), while the other 4 proteins conferred risk on critical COVID-19 only (OR: 1.07~1.16), including EIF4EBP1, IL-7, NTF3, and LIF. Meanwhile, five proteins exert protective effects against hospitalization and progression to critical COVID-19 (OR: 0.85~0.95), including CXCL11, CDCP1, CCL4/MIP, IFNG, and LIFR. Sensitivity analyses did not support the presence of heterogeneity in the majority of MR analyses.

Conclusions

Our study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease.

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