Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19
ObjectiveThe 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.MethodsWe performed Mendelian randomization (MR) analysis usi...
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| Format: | Article |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1352583/full |
| _version_ | 1797300316889153536 |
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| author | Ancha Baranova Ancha Baranova Jing Luo Jing Luo Li Fu Guanqun Yao Fuquan Zhang Fuquan Zhang |
| author_facet | Ancha Baranova Ancha Baranova Jing Luo Jing Luo Li Fu Guanqun Yao Fuquan Zhang Fuquan Zhang |
| author_sort | Ancha Baranova |
| collection | DOAJ |
| description | ObjectiveThe 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.MethodsWe 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.ResultsWe 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.ConclusionsOur study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease. |
| first_indexed | 2024-03-07T23:05:31Z |
| format | Article |
| id | doaj.art-d3b2c6b9d04243ddb1ae99c66f44975c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T23:05:31Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d3b2c6b9d04243ddb1ae99c66f44975c2024-02-22T04:54:28ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13525831352583Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19Ancha Baranova0Ancha Baranova1Jing Luo2Jing Luo3Li Fu4Guanqun Yao5Fuquan Zhang6Fuquan Zhang7School of Systems Biology, George Mason University, Manassas, VA, United StatesResearch Centre for Medical Genetics, Moscow, RussiaDepartment of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, ChinaSchool of Medicine, Tsinghua University, Beijing, ChinaDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, ChinaSchool of Clinical Medicine, Tsinghua University, Beijing, ChinaDepartment of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, ChinaInstitute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, ChinaObjectiveThe 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.MethodsWe 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.ResultsWe 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.ConclusionsOur study revealed risk and protective inflammatory proteins for severe COVID-19, which may have vital implications for the treatment of the disease.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1352583/fullcirculating inflammatory proteinMendelian randomizationCOVID-19GWASLIFR |
| spellingShingle | Ancha Baranova Ancha Baranova Jing Luo Jing Luo Li Fu Guanqun Yao Fuquan Zhang Fuquan Zhang Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19 Frontiers in Immunology circulating inflammatory protein Mendelian randomization COVID-19 GWAS LIFR |
| title | Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19 |
| title_full | Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19 |
| title_fullStr | Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19 |
| title_full_unstemmed | Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19 |
| title_short | Evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe COVID-19 |
| title_sort | evaluating the effects of circulating inflammatory proteins as drivers and therapeutic targets for severe covid 19 |
| topic | circulating inflammatory protein Mendelian randomization COVID-19 GWAS LIFR |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1352583/full |
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