Cytokine Signature Associated With Disease Severity in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1β were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-β were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.

Keywords: COVID-19; SARS-CoV-2; biomarker; disease severity; hypercytokinaemia.

Figure 1

Comparison of serum cytokine concentrations between COVID-19 patients, H1N1 patients and healthy controls. Serum from COVID-19 patients (N=75), H1N1 patients (N=23) and healthy controls (N=34) were collected and 48 kinds of cytokines were measured. The horizontal line represents the median. Of the cytokine examined, 33 cytokines were significantly increased in COVID-19 patients when compared with the healthy controls, 29 cytokines were significantly increased in the COVID-19 group compare with H1N1 group. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 2

Correlations between serum cytokine level and virus titers in COVID-19 patients. The virus quantitative detection results were expressed by CT value for the SARS-CoV-2 gene by quantitative real-time reverse transcription-PCR as previously described. Viral loads from 35 patients within 2 weeks after disease onset were acquired. The levels of 3 cytokines, including IP-10, HGF and IL-10, were positively correlated with the virus titers.

Figure 3

Comparison of serum cytokine concentrations between COVID-19 patients with different severity of illness. Serum samples from critically ill (N=17), severe (N=30), and mild (N=28) COVID-19 patients were collected at the earliest possible time point after hospitalization for assays measuring the concentrations of 48 cytokines. 2 cytokines with significantly increase in severe cases when compared with mild type, including G-CSF and M-CSF. 2 cytokines with significantly increase in critical cases when compared with mild type, including IP-10 and M-CSF. *P < .05, **P < .01.