Cytokine Elevation in Severe COVID-19 From Longitudinal Proteomics Analysis: Comparison With Sepsis

被引：27

作者：

Ebihara, Takeshi ^{[1
]}

Matsumoto, Hisatake ^{[1
]}

Matsubara, Tsunehiro ^{[1
]}

Togami, Yuki ^{[1
]}

Nakao, Shunichiro ^{[1
]}

Matsuura, Hiroshi ^{[1
,2
]}

Kojima, Takashi ^{[3
]}

Sugihara, Fuminori ^{[4
,5
]}

Okuzaki, Daisuke ^{[6
]}

Hirata, Haruhiko ^{[7
]}

Yamamura, Hitoshi ^{[2
]}

Ogura, Hiroshi ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Traumatol & Acute Crit Med, Suita, Osaka, Japan

[2] Osaka Prefectural Nakakawachi Emergency & Crit Ca, Higashiosaka, Osaka, Japan

[3] Osaka Univ Hosp, Lab Clin Invest, Suita, Osaka, Japan

[4] Osaka Univ, Immunol Frontier Res Ctr, Core Instrumentat Facil, Osaka, Japan

[5] Osaka Univ, Res Inst Microbial Dis, Osaka, Japan

[6] Osaka Univ, Res Inst Microbial Dis, Genome Informat Res Ctr, Osaka, Japan

[7] Osaka Univ, Grad Sch Med, Dept Resp Med & Clin Immunol, Suita, Osaka, Japan

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 12卷

基金：

日本学术振兴会;

关键词：

biomarkers; COVID-19; cytokines; GDF-15; IL-6; mechanical ventilation; ANTIINFLAMMATORY CYTOKINE; IL-6; INFLAMMATION;

D O I：

10.3389/fimmu.2021.798338

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

IntroductionCoronavirus disease 2019 (COVID-19) is a new viral disease. Uncontrolled inflammation called "cytokine storm" is reported to contribute to disease pathogenesis as well as sepsis. We aimed to identify cytokines related to the pathogenesis of COVID-19 through a proteomics analysis of 1463 plasma proteins, validate these cytokines, and compare them with sepsis. Materials and MethodsIn a derivation cohort of 306 patients with COVID-19, 1463 unique plasma proteins were measured on days 1, 4, and 8. Cytokines associated with disease severity and prognosis were derived. In a validation cohort of 62 COVID-19 patients and 38 sepsis patients treated in the intensive care unit [ICU], these derived cytokines were measured on days 1 (day of ICU admission), 2-3, and 6-8 (maximum: 3 time points/patient). Derived cytokines were compared with healthy controls and between COVID-19 and sepsis patients, and the associations with prognosis were evaluated. The time to wean off mechanical ventilation (MV) was evaluated only for COVID-19. ResultsIL-6, amphiregulin, and growth differentiation factor (GDF)-15 were associated with disease severity and prognosis in the derivation cohort. In the validation cohort, IL-6 and GDF-15 were elevated in COVID-19 and sepsis on day 1, and the levels of these cytokines were higher in sepsis than in COVID-19. IL-6 and GDF-15 were associated with prognosis in sepsis. Cox proportional hazards model with time as a dependent covariate showed a significant relationship between plasma GDF-15 level and time to wean off MV (hazard ratio, 0.549 [95% confidence level, 0.382-0.789]). The GDF-15 level at ICU admission predicted late recovery. ConclusionGDF-15 and IL-6 derived from proteomics analysis were related with disease severity of COVID-19. Their values were higher in sepsis than in COVID-19 and were associated with prognosis in sepsis. In COVID-19 patients treated in the ICU, GDF-15 was associated with the time to wean off MV and better predicted late recovery.

引用

页数：11

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