Comparison of the levels of neopterin, CRP, and IL-6 in patients infected with and without SARS-CoV-2

Abstract

Background: Neopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers especially in relatively early phase of patients to reveal the significance of NP measurements in pathological states.

Methods: Plasma NP, biopterin, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 23 patients with non-COVID-19 disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently.

Results: The NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while biopterin, CRP and IL-6 were not changed significantly. The NP levels were found to show a weak negative correlation against the days after onset in the COVID-19 patients (rs = -0.348, p = 0.0192), suggesting that the elevation of NP would be an early event of viral infection. Correlations between NP and CRP, or between NP and IL-6 in COVID-19 patients were weaker than that between CRP and IL-6.

Conclusions: The elevation of NP levels was supposed to be distinct from those of CRP and IL-6 in relatively early and mild COVID-19 patients. Our data suggest that NP is produced at the early phase of infection by different signaling pathways and/or cells from those of CRP and IL-6. Further study on the signaling pathway to induce NP is expected.

Keywords: Biomarker; COVID-19; CRP; IL-6; Neopterin; SARS-CoV-2; Viral infection.

Figure 1

Conversion of H₂NP to NP in PBS (A) and in human plasma (B). (A) H₂NP in PBS was place on the autosampler at 10 °C in the dark, and then analyzed by HPLC with post-column oxidation method at times indicated. (B) Exogenous H₂NP was added to plasma. After deproteinization, samples were analyzed. PBS was added instead of H₂NP for the preparation of the plasma alone sample.

Figure 2

Concentrations of plasma NP, BP, CRP and IL-6 in COVID-19 (n = 46 for NP and BP, and n = 45 for CRP and IL-6) and non-COVID-19 patients (n = 23 in non-COVID-19 patients for NP, BP and IL-6 and 22 for CRP). ∗∗p < 0.01, Mann–Whitney U test. The boxes represent the median and interquartile ranges. Whiskers represent minimum and maximum 1.5 interquartile range and dots are outliers.

Figure 3

Concentrations of plasma NP, BP, CRP and IL-6 in COVID-19 patients with mild (n = 7), moderate (n = 15), severe (n = 21 for NP and BP, and n = 20 for CRP and IL-6) and critical (n = 3) symptoms. ∗p < 0.05, ∗∗p < 0.01, Kruskal–Wallis test with Steel-Dwass post hoc test. The boxes represent the median and interquartile ranges. Whiskers represent minimum and maximum 1.5 interquartile range and dots are outliers.

Figure 4

Concentrations of NP, CRP and IL-6 in COVID-19 patients after the onset of symptoms expressed as days. n = 46, 45 and 45, respectively. Spearman's correlation coefficients (rs) and p-values are shown in the plots.

Figure 5

Correlations among NP, CRP and IL-6 in COVID-19 (A) and non-COVID-19 (B) patients. n = 45 in each panel in COVID-19 patients. n = 23 for IL-6-NP and n = 22 for CRP-NP and CRP-IL-6 in non-COVID-19 patients. Spearman's correlation coefficients (rs) and p-values are shown in the plots.