Certain Cytokines Not Associated with Severity of COVID-19 Symptoms

The pandemic outbreak of coronavirus disease 2019 (COVID-19) is sharply spreading all over the world. The severity of a viral disease usually is positive association with immune-mediated inflammatory responses. The aggressive and persistent inflammatory response leads to high risk of multiorgan failure and death.

The overproduction inflammatory cytokines results in cytokine storm. Cytokine storm indicates excessive release of pro-inflammatory cytokines including C-reactive protein (CRP) and pro-inflammatory cytokines (IL-2, IL-4, TNF-α, IFN-γ). There is a body of evidences suggests that severe COVID-19 patients have cytokine storm.

Scientists at the Harbin Medical University (Harbin, China) and their colleagues studied patients aged 39 to 85 years old, who were confirmed to be SARS-CoV-2 positive via nasopharyngeal swabs. Further, clinical characteristics and chest CT scans indicated that these patients had severe COVID-19. All patients were admitted in ICU with hypoxemic respiratory failure. Of these patients, five (20%) had hypertension and five (20%) had diabetes. All 25 patients were discharged from the ICU to the hospital ward before being discharged home.

The scientists analyzed serum inflammatory cytokines and immune cells in these patients and found that CRP (range: 0.499-9.75 mg/L; reference value: 0-10 mg/L), IL-2 (range: 0.67-2.59 pg/L; reference value: 0.08-5.71 pg/mL), IL-4 (range: 0-2.27 pg/L; reference value: 0.1-2.8 pg/L), TNF-α (range: 0-1.86 pg/L; reference value: 0.1-2.31 pg/L) and IFN-γ (range: 0.51-3.24 pg/L; reference value: 0.16-7.42 pg/L) were in the normal value range compared to the reference value. These cases showed that IL-2, IL-4, TNF-α, IFN-γ and C reactive protein level is not associated with severe COVID-19 pathology.

The investigators also reported that levels of IL-6 and IL-10 in some severe COVID-19 patients were over the reference values, indicating that these patients had severe clinical characteristics independent of circulating levels of IL-2, IL-4, TNF-α, IFN-γ and CRP. IL-6 levels in 16 patients were above the reference range of 1.18-5.3 pg/L, with levels of 0-36.3 pg/L recorded in all 25 patients. In addition, 14 patients had IL-10 levels above the reference range of 0.19-4.91 pg/L, with levels of 4.96-12.44 pg/L observed across the 25 patients.

The authors concluded that some reports had shown cytokine storm was correlated with severity and mortality of COVID-19 patients, but the correlation does not indicate causation. More viral replication also could drive consequent severity of COVID-19. The authors said that the hypothesis that blocking cytokine storm eases COVID-19 severity needs to be more carefully investigated based on their observation. The study was published on June 10, 2020 in the Journal of Medical Virology.

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Harbin Medical University