[Analysis of the changes of inflammatory cytokine levels in patients with critical coronavirus disease 2019 undergoing invasive mechanical ventilation].

Objective: To investigate the relationship between the changes of inflammatory cytokine levels and prognosis of patients with critical coronavirus disease 2019 (COVID-19) undergoing invasive mechanical ventilation (IMV).

Methods: A retrospective study was conducted. The clinical date of critical COVID-19 patients undergoing IMV who were hospitalized in Wuhan Union Hospital, Tongji Medical College of Huazhong University of Science and Technology from February 4th to March 25th in 2020 were collected. At the same time, the inflammatory cytokine levels including interleukins (IL-2, IL-4, IL-6, IL-10) and tumor necrosis factor-α (TNF-α) at 48 hours before IMV and 48 hours after IMV of all the patients, as well as the 48 hours after weaning or right before death were recorded. Multivariate unconditional Logistic regression analysis was used to screen the independent risk factors of death during hospitalization.

Results: Among the 43 patients, 13 patients improved and 30 died. Compared with the survival group, the patients in the non-survival group were older (years old: 67.6±7.3 vs. 58.5±11.9, P < 0.05), with higher rates of hypertension, diabetes and coronary heart disease (53.3% vs. 15.4%, 63.3% vs. 23.1%, 26.7% vs. 0%, all P < 0.05), and the time from onset to admission to hospital, admission to ICU and IMV were longer (days: it was 9.17±5.00 vs. 5.07±2.49, 17.10±7.11 vs. 12.23±5.05, and 17.90±7.46 vs. 12.61±5.60, respectively, all P < 0.05). The IL-6 and TNF-α levels on 48 hours after IMV in the non-survival patients increased significantly as compared with those before 48 hours and the surviving patients. Especially, the IL-6 levels increased significantly as compared with those at 48 hours after IMV and 48 hours after weaning in the surviving patients [ng/L: 800.00 (194.25, 2 000.00) vs. 22.03 (6.66, 28.21), 3 204.00 (1 264.88, 5 000.00) vs. 5.00 (3.98, 12.27), both P < 0.01]. The IL-10 level before death in the non-survival patients increased significantly as compared with that at 48 hours after weaning in the surviving patients [ng/L: 55.89 (26.07, 100.14) vs. 3.53 (2.76, 12.36), P < 0.05]. There were no significant differences in the levels of IL-2 and IL-4 between the two groups at every time point. The variables of age, basic diseases, the IL-6 level after IMV were included in the multivariate unconditional Logistic regression analysis, which showed that age [odds ratio (OR) = 0.821, 95% confidence interval (95%CI) was 0.695-0.968], hypertension (OR = 0.027, 95%CI was 0.002-0.378), diabetes mellitus (OR = 0.054, 95%CI was 0.005-0.611), coronary heart disease (OR = 0.042, 95%CI was 0.002-0.968) and the IL-6 level after IMV (OR = 0.902, 95%CI was 0.819-0.994) were independent risk factors for death during hospitalization in patients with critical COVID-19 undergoing IMV (all P < 0.05).

Conclusions: The levels of inflammatory cytokine including IL-6, IL-10, and TNF-α increased significantly with aggravation in critical COVID-19 patients undergoing IMV, especially IL-6. IL-6 was an independent risk factor for death of critical COVID-19 patients undergoing IMV.