Cytokine levels as predictors of mortality in critically ill patients with severe COVID-19 pneumonia: Case-control study nested within a cohort in Colombia

Background: High levels of different cytokines have been associated in COVID-19 as predictors of mortality; however, not all studies have found this association and its role to cause multi-organ failure and death has not been fully defined. This study aimed to investigate the association of the levels of 10 cytokines with mortality in patients with COVID-19 admitted to the intensive care unit (ICU). Materials and methods: This is a case-control study nested within a cohort of patients with COVID-19 who were on mechanical ventilation and were not hospitalized for more than 48 h across nine ICUs in Medellín, Colombia. Serum samples were collected upon admission to the ICU and 7 days later and used to measure cytokine levels. Results: Upon admission, no differences in mortality between the cytokine levels were observed when comparisons were made quantitatively. However, in the multivariate analysis, patients with median IL-1β levels <1.365 pg/ml showed an increase in mortality (OR = 3.1; 1.24<7.71; p = 0.015). On day 7 in the ICU, IL-1β median levels were lower (0.34 vs. 2.41 pg/ml, p = 0.042) and IL-10 higher (2.08 vs. 1.05 pg/ml, p = 0.009) in patients who died. However, in the multivariate analysis, only IL-12p70 was associated with mortality (OR = 0.23; 0.07<0.73; p = 0.012). The mean difference in the levels between day 1 and day 7 decreased in both IFN-γ (3.939 pg/ml, p < 0.039) and in IL-18 (16.312 pg/ml, p < 0.014) in the patients who died. A low IL-1β/IL-10 ratio was associated with mortality on both day 1 and day 7, while an IL-1β/IL-10 ratio below the cut-off on day 7 was associated with decreased survival. The lowest TNFα/IL-10 ratio was associated with mortality only on day 7. Conclusion: At the time of admission, patients with median IL-1β levels lower than 1.365 pg/ml had increased mortality. An IL-1β/IL-10 ratio <2 at day 7 and IL-12p70 levels >1.666 pg/ml was associated with decreased survival.