Cytokine levels in predicting severity and outcome of COVID-19: a non-randomized clinical trial of hospital cases

Background: Coronavirus disease 2019 (COVID-19) is a multisystem disease caused by severe immune response dysregulation, which leads to the overproduction of proinflammatory cytokines and a cytokine storm. The most significant mediators of systemic inflammation are IL-6, IL-8, and IL-10, as well as IFN-α and IFN-γ. Levels of these mediators reflect the degree of activation of the inflammatory cascade and the severity of damage to target organs. Detecting cytokine abnormalities at admission can predict and facilitate early risk stratification for adverse outcomes, which is especially important during periods of high strain on the healthcare system.

Aim: This study aimed to evaluate the levels of key proinflammatory cytokines in 617 patients with confirmed COVID-19 to assess the severity of the acute inflammatory response and its correlation with disease severity and clinical outcomes.

Methods: This was a non-randomized clinical study of 617 hospital cases, including 255 men and 362 women aged 59–78 years, who were admitted to the Infectious Diseases Hospital of the Bashkir State Medical University Clinic from 2020 to 2021. Patients were grouped by disease severity: moderate (n = 502), severe (n = 67), and fatal (n = 18). On day 1 of hospitalization, levels of IL-1, IL-6, IL-8, IL-10, IFN-α, and IFN-γ were measured in serum samples using an enzyme-linked immunosorbent assay (Vector-Best JSC). Statistical analysis was performed using Statistica 10 and StatTech 4.0.7 with ROC modeling to determine predictive cutoffs.

Results: Most of those who died were over 68 years old, and the risk of death increased significantly for those over 74 years old. A higher mortality rate was observed in patients who were hospitalized for less than 13 inpatient days (p = 0.042). Significantly higher levels of IL-6 and IL-10 were reported in severe and fatal cases (p < 0.001). The level of IFN-γ was significantly lower in fatal cases (p < 0.024). The decrease in IFN-α and IFN-γ levels indicated an inadequate interferon response. A ROC analysis identified the following predictive threshold cutoffs for a fatal outcome: IFN-α ≥ 7.292, IL-10 ≥ 8.796, and IL-6 ≥ 23.061.

Conclusion: The COVID-19 severity and mortality were associated with higher levels of proinflammatory interleukins (IL-6 and IL-10) and lower levels of interferons (IFN-α and IFN-γ). These parameters can be considered predictive biomarkers, which could improve management strategies and enable early risk stratification.