Serum Cytokine Concentrations Early in COVID-19 Infection as Biomarker of Disease Severity

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Study authors measured serum cytokine levels of COVID-19 patients during the acute phase, and determined if IL-12 and IL-2 would be determinant of more severe disease progression.

Serum cytokine levels during the acute phase of a SARS-CoV-2 infection may be indicative of disease severity, according to findings were published in The Journal of Infectious Diseases.

Patients (N=95) in the acute phase of a SARS-CoV-2 infection and healthy employees (n=20) were recruited from Hyogo Prefectural Kakogawa Medical Center in Japan between July and September, 2020. Blood samples were assessed for cytokines, chemokines, and growth factor.

Patients were a mean age of 50 years (range, 15-98), 52 participants were men, and their COVID-19 disease severities were categorized as mild (n=49), moderate (n=11), severe (n=19), and asymptomatic (n=16). A total of 20 healthy participants included; the median age was 57 years (range, 27-64) and 13 participants were men.

Levels of interleukin (IL)-12 and IL-2 were significantly elevated among patients with asymptomatic or mild infections compared with moderate or severe infections (IL-12, all P <.0001; IL-2, all P <.05).

Levels of IL-18 and IL-6 tend to have a dose-response pattern, in which healthy controls, asymptomatic, or mild patients had lower levels compared with patients who had moderate or severe infections (all P <.05).

The serum levels of IL-15 and IL-2Ra were significantly elevated among patients with SARS-CoV-2 compared with controls (IL-15, all P <.0001; IL-2Ra, all P <.005) but did not differ among severity levels. This pattern was similar for other IL cytokines (IL-1Ra, IL-7, IL-10, IL-13, IL-1a, and IL-16), interferon-g, tumor necrosis factor-a, platelet-derived growth factor-BB, and monocyte chemoattractant protein-1.

This study was limited by its small sample size and by not including information on baseline characteristics, treatments, or SARS-CoV-2 outcomes.

These results were consistent with previous analyses which observed that IL-6 was decreased among severely ill patients with SARS-CoV-2. Altogether, these data emphasized the importance of blood serum cytokines and chemokines during the disease course of SARS-CoV-2 and indicated that blood cytokines may be biomarkers for severity of infection.


Tjian L H, Furukawa K, Nagano T, et al. Early differences in cytokine production distinguish severity of COVID-19. J Infect Dis. 2021;jiab005. doi:10.1093/infdis/jiab005.