Laboratory diagnostic value of neopterin measurements in patients with COVID-19 infection

The new coronavirus SARS-CoV-2 was identified to be responsible for the COVID-19 pandemic. There are striking differences in the response to infection, some people develop no or mild symptoms, while other outcomes are severe of even fatal. For those COVID-19 patients who require hospitalization, prognostic markers could help clinicians to identify patients with a poor outcome early. The serum levels of the immune activation marker neopterin have already been shown to be of prognostic value in patients with SARS-CoV-1 and a similar pattern can be observed for SARS-CoV-2. This comment discusses the biochemical circuits that support the clinical value of neopterin measurements in COVID-19 patients.

Serum Neopterin Levels and the Clinical Presentation of COVID-19

In Coronavirus disease 2019 (COVID-19), it is important to evaluate disease activity and investigate possible biomarkers. Therefore, in this study, we investigated the relationship between disease activity and serum levels of possible immune activation marker neopterin in patients with COVID-19. The study enrolled 45 patients (23 females, 51.1%) treated for COVID-19. The patients were divided into two groups according to their clinical presentation: those who recovered quickly (Group 1) and those who worsened progressively (Group 2). The neopterin and C-reactive protein levels were high in all patients on admission. In Group 1, neopterin concentrations and serum neopterin/creatinine ratios were significantly higher on admission compared to Day 14 of the disease, whereas in Group 2, levels were significantly higher at Day 14 of the disease than on admission. Neopterin levels at admission were significantly higher in Group 1. The serum neopterin concentrations at admission were markedly higher in patients with a derived neutrophil–lymphocyte ratio (dNLR) > 2.8 compared to those with a dNLR ≤ 2.8 (p < 0.05). Serum neopterin levels can be used as a prognostic biomarker in predicting disease activity in COVID-19.

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

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.

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

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 clinical praxis.

Diet Quality Is Low and Differs by Sex in People with HIV

ABSTRACT Background People with HIV (PWH) are at risk for developing metabolic comorbidities driven, in part, by immune activation/inflammation. Little is known about diet quality, a potential modifiable factor in PWH. Objectives This study aimed to explore diet quality in terms of conformance with US dietary guidelines by calculating Healthy Eating Index-2010 (HEI) scores among adults with and without HIV in Boston, MA, and determine associations with HEI and markers of immune activation/inflammation. Methods One-hundred and three HIV-infected [50 women, 53 men; mean ± SD age: 47 ± 7 y; body mass index (BMI, in kg/m2): 26 ± 5] and 38 uninfected adults (17 women, 21 men; age: 46 ± 7 y; BMI: 28 ± 4) were included in this cross-sectional analysis. Participants who completed a 4-d food record from which HEI could be calculated were included. HEI was compared between participants with and without HIV, within HIV-infected participants stratified by sex, and by HIV serostatus and sex. In the HIV group, predictors of HEI were determined in multivariable modeling. Univariate associations with diet quality and inflammation/immune markers were assessed. Results The HEI score was 51.3 in the HIV-infected participants and 57.3 in the HIV-uninfected participants (P = 0.052). In the comparison by HIV serostatus and sex, HIV-infected women had significantly lower HEI (49.2) compared with HIV-infected men (55.7) (P = 0.005) and HIV-uninfected men (61.8) (P = 0.002). Adjusting for potential confounding factors, sex remained an independent predictor of HEI in HIV (P = 0.02). In the HIV group, higher log HEI was associated with lower concentration of the immune activation marker sCD14 (P = 0.009). Conclusions Diet quality tended to be lower in HIV-infected individuals compared with HIV-uninfected individuals and was lower among HIV-infected women compared with HIV-infected men, and HIV-uninfected men. There may also be an association with diet quality and sCD14 in PWH. Future prospective studies are needed to confirm these findings and determine whether improving diet quality is a useful strategy to reduce metabolic abnormalities in this population. This study was registered at clinicaltrials.gov as NCT00455793.

Accelerated Tryptophan Degradation Predicts Poor Survival in Trauma and Sepsis Patients

Immune system activation and inflammation accompanies immune dysfunction in trauma and sepsis patients. Immunodeficiency may develop in such patients as one consequence of an activated chronic pro-inflammatory response. According to recent data, degradation of L-tryptophan (TRP) via the kynurenine (KYN) pathway by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO) could represent an important contributor to the deficient responsiveness of immunocompetent cells. Compared to healthy controls, patients post trauma or with sepsis had increasing KYN concentrations and KYN to TRP ratios (KYN/TRP) whereas TRP concentrations decreased. Likewise, concentrations of cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and of immune activation marker neopterin increased in patients (all p < 0.001). Furthermore in patients KYN/TRP, KYN and neopterin concentrations were further increasing (all p < 0.001), whereas the changes of TRP, TNF-α and IL-6 concentrations were not significant. Compared to the survivors, the non-survivors had a higher concentration of KYN, neopterin, TNF-α and IL-6 as well as a higher KYN/TRP ratio. KYN/TRP correlated with neopterin (p < 0.001) and also with TNF-α (p < 0.01) and IL-6 concentrations (p < 0.05) and inversely with the in vitro response of stimulated monocytes. We conclude that increased TRP degradation in patients post trauma is closely associated with immune activation. Cytokines released during the pro-inflammatory response may induce the activity of IDO and thus accelerate TRP degradation. Thus, increased IDO activity most likely represents a result of host response to pro-inflammation in patients. Data support a possible role of inflammation-induced IDO in the diminished immunoresponsiveness in patients.

Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors

Immune dysfunction in trauma patients is associated with immune system activation and inflammation. The cytokine-inducible enzyme IDO (indoleamine 2,3-dioxygenase) initiates the degradation of the essential aromatic amino acid tryptophan via the kynurenine pathway and could contribute to deficient immune responsiveness. Activated IDO is indicated by an increased kyn/trp (kynurenine/tryptophan) ratio. The aim of the present study was to investigate whether tryptophan degradation is associated with outcome in patients post-trauma. Tryptophan and kynurenine concentrations were measured by HPLC in serum specimens of 15 patients post-trauma during 12–14 days of follow-up. Up to five samples within this observation period from each patient were included in this analysis, and a total a 69 samples were available. For further comparisons, concentrations of the immune activation marker neopterin were measured. Compared with healthy controls, the average kyn/trp ratio and kynurenine concentrations were increased in patients, whereas tryptophan concentrations were decreased. During follow-up, increased kyn/trp ratio and kynurenine concentrations (all P<0.001) were observed, whereas the changes in tryptophan concentrations were not significant. Non-survivors had higher kyn/trp ratios and kynurenine concentrations compared with survivors. The kyn/trp ratio correlated with neopterin concentrations (rs=0.590, P<0.001). In conclusion, these results imply that increased tryptophan degradation in patients is due to activated IDO, which most probably is a consequence of a host defence response. These findings support a possible role for IDO in the development of immunodeficiency and death in patients.