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

• Published in: Frontiers in immunology Vol. 12; p. 798338
• Main Authors: Ebihara, Takeshi, Matsumoto, Hisatake, Matsubara, Tsunehiro, Togami, Yuki, Nakao, Shunichiro, Matsuura, Hiroshi, Kojima, Takashi, Sugihara, Fuminori, Okuzaki, Daisuke, Hirata, Haruhiko, Yamamura, Hitoshi, Ogura, Hiroshi
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12-01-2022
• Subjects: Aged; Aged, 80 and over; biomarkers; Cohort Studies; COVID-19; COVID-19 - blood; COVID-19 - immunology; Cytokine Release Syndrome - blood; Cytokine Release Syndrome - immunology; Cytokine Release Syndrome - virology; cytokines; Cytokines - blood; Cytokines - immunology; Female; GDF-15; Growth Differentiation Factor 15 - immunology; Humans; IL-6; Immunology; Inflammation - blood; Inflammation - immunology; Inflammation - virology; Intensive Care Units; Male; mechanical ventilation; Middle Aged; Prognosis; Proteomics - instrumentation; Respiration, Artificial - methods; SARS-CoV-2 - immunology; Sepsis - blood; Sepsis - immunology; Sepsis - virology; Severity of Illness Index; COVID-19; cytokines; mechanical ventilation; biomarkers; GDF-15; IL-6
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.798338

Coronavirus 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.
In 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.
IL-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.
GDF-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.