Serum neopterin levels in relation to mild and severe COVID-19

Abstract

Background: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19.

Methods: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion.

Results: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases.

Conclusions: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.

Keywords: COVID-19; Kynurenine; Neopterin; Prognostic markers; Tryptophan.

Fig. 1

Concentrations of first measurements of serum neopterin, tryptophan, and kynurenine, as well as kynurenine to tryptophan ratio (K/T) in patients with mild (green) and severe (red) form of COVID-19 (n = 34). The dashed line represents the upper normal reference limit of neopterin at 9.1 nmol/L.

Fig. 2

First measurements of serum neopterin concentrations in patients with mild (green) and severe (red) form of COVID-19 (n = 34). The dashed line represents the upper normal reference limit of neopterin at 9.1 nmol/L.

Fig. 3

Repeated measurements of serum neopterin concentrations in patients with mild (green) and severe (red) form of COVID-19 (n = 34). Severity (mild/severe), days since symptom onset, and age were used as covariates in the linear mixed effect model. The black dashed line represents the upper normal reference limit of neopterin at 9.1 nmol/L.

Fig. 4

The correlation between first measurements of serum neopterin (S Neopt) concentration and kynurenine to tryptophan ratio (K/T) in patients suffering from COVID-19 (n = 34)