Changes in micronutrient and inflammation serum biomarker concentrations after a norovirus human challenge

Abstract

Background To accurately assess micronutrient status, it is necessary to characterize the effects of inflammation and the acute-phase response on nutrient biomarkers. Objective Within a norovirus human challenge study, we aimed to model the inflammatory response of C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) by infection status, model kinetics of micronutrient biomarkers by inflammation status, and evaluate associations between inflammation and micronutrient biomarkers from 0 to 35 d post–norovirus exposure. Methods Fifty-two healthy adults were enrolled into challenge studies in a hospital setting and followed longitudinally; all were exposed to norovirus, half were infected. Post hoc analysis of inflammatory and nutritional biomarkers was performed. Subjects were stratified by inflammation resulting from norovirus exposure. Smoothed regression models analyzed the kinetics of CRP and AGP by infection status, and nutritional biomarkers by inflammation. Linear mixed-effects models were used to analyze the independent relations between CRP, AGP, and biomarkers for iron, vitamin A, vitamin D, vitamin B-12, and folate from 0 to 35 d post–norovirus exposure. Results Norovirus-infected subjects had median (IQR) peak concentrations for CRP [16.0 (7.9–29.5) mg/L] and AGP [0.9 (0.8–1.2) g/L] on day 3 and day 4 postexposure, respectively. Nutritional biomarkers that differed (P < 0.05) from baseline within the inflamed group were ferritin (elevated day 3), hepcidin (elevated days 2, 3), serum iron (depressed days 2–4), transferrin saturation (depressed days 2–4), and retinol (depressed days 3, 4, and 7). Nutritional biomarker concentrations did not differ over time within the uninflamed group. In mixed models, CRP was associated with ferritin (positive) and serum iron and retinol (negative, P < 0.05). Conclusion Using an experimental infectious challenge model in healthy adults, norovirus infection elicited a time-limited inflammatory response associated with altered serum concentrations of certain iron and vitamin A biomarkers, confirming the need to consider adjustments of these biomarkers to account for inflammation when assessing nutritional status. These trials were registered at clinicaltrials.gov as NCT00313404 and NCT00674336.

Hepcidin-Mediated Hypoferremia Disrupts Immune Responses to Vaccination and Infection

“…Hepcidin, Hypoferremia, and Viral Infections Hepcidin-controlled iron redistribution protects against some bacterial infections and malaria in mice. 29,30 In humans, increased hepcidin and hypoferremia occur after experimental norovirus, typhoid, and malaria infections, [31][32][33] and during the initial emergence of viremia in HIV-1-infected blood donors. 34 Although inflammatory hypoferremia can be beneficial in the context of infections with single-cell organisms that must acquire iron from their host, evidence that low serum iron is protective in the context of viral infections is lacking.…”

High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study

“…Although we did not directly show the effect of HDIVC on cytokines, we have demonstrated the shorter duration of SIRS and less SIRS prevalence in the HDIVC compared to the control group during the first week after admission. Serum levels of CRP are usually used to track and monitor the inflammatory response caused by infection due its short half-life of 19 h (Williams et al, 2019). CRP levels were shown to be reduced rapidly by HDIVC (200 mg/kg/day) in a previous before-after study in a cohort of sepsis patients (Fowler et al, 2014).…”

Adjusting iron and vitamin A status in settings of inflammation: a sensitivity analysis of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) approach

“…Recent data from longitudinal studies support the changes we have observed in micronutrient biomarker concentrations related to the acute-phase proteins. For example, in a norovirus challenge study of healthy adults, ferritin concentrations increased, and retinol and RBP concentrations decreased, in response to temporary elevations in AGP and CRP ( 25 ). No changes in micronutrient biomarkers were observed among uninflamed individuals over time, which further suggests that iron and vitamin A biomarker concentration changes in the inflamed group were temporal and not reflective of underlying nutritional status ( 25 ).…”

“…For example, in a norovirus challenge study of healthy adults, ferritin concentrations increased, and retinol and RBP concentrations decreased, in response to temporary elevations in AGP and CRP ( 25 ). No changes in micronutrient biomarkers were observed among uninflamed individuals over time, which further suggests that iron and vitamin A biomarker concentration changes in the inflamed group were temporal and not reflective of underlying nutritional status ( 25 ). A study among asymptomatic children in Burkina Faso found that short-term, within-individual changes in ferritin and RBP in relation to AGP and CRP were similar to between-individual cross-sectional differences, supporting the validity of inflammation adjustment approaches in cross-sectional surveys ( 26 ).…”