Evaluation of iron metabolism in hospitalized COVID-19 patients.

BACKGROUND: Iron metabolism dysregulation may play a role in organ failure observed in Coronavirus disease 2019 (COVID-19). This study aimed to explore the whole iron metabolism in hospitalized COVID-19 patients and evaluate the impact of tocilizumab. METHODS: We performed an observational multicentric cohort study, including patients with PCR-provenCOVID-19 from the intensive care unit (ICU) (n = 66) and medical ward (n = 38). We measured serum interleukin-6 (IL-6), ferritin, glycosylated ferritin (GF), transferrin, iron, and hepcidin. The primary outcome was death. RESULTS: Among the 104 patients, we observed decreased median GF percentage (35 %; IQ 23-51.5), low iron concentration (7.5 µmol/L; IQ 4-14), normal but low transferrin saturation (TSAT; 21%; IQ 11-33) and increased median hepcidin concentration (58.7 ng/mL; IQ 20.1-92.1). IL-6, ferritin, and GF were independently and significantly associated with death (p = 0.026, p = 0.023, and p = 0.009, respectively). Surprisingly, we observed a decorrelation between hepcidin and IL-6 concentrations in some patients. These findings were amplified in tocilizumab-treated patients. CONCLUSION: Iron metabolism is profoundly modified in COVID-19. The pattern we observed presents differences with a typical inflammation profile. We observed uncoupled IL-6/hepcidin levels in some patients. The benefit of additive iron chelation therapy should be questionable in this setting.

Clinically relevant urine creatinine underestimation in the low concentration range on the Siemens Dimension Vista®.

While considerable efforts have been accomplished to standardize the measurement of plasma creatinine (PCr), urine creatinine (UCr) has not been subject to the same scrutiny. UCr is importantly used when measuring biomarkers in spot urines, to assess urine output and variable dilution of urine samples. Here, we report underestimation of Jaffe UCr measurements on the Siemens Dimension Vista® analyzer, critically affecting samples with UCr ≤2 mmol/L. We demonstrate that this error is caused by automatic urine pre-dilution by the Vista's «urine mode¼, and that UCr measured in «plasma mode¼ without pre-dilution does not present this error. In the absence of a comprehensive solution proposed by Siemens, we propose simple formulae that can be easily implemented in a laboratory to correct these low UCr measurements. Importantly, the observed UCr underestimation can significantly influence reported results for biomarkers/UCr ratios measured in spot urine. Indeed, these results can be overestimated up to +84.4 % before correction using our formulae. This can sometimes lead to misclassification according to clinical thresholds, e.g. Kidney disease: improving global outcomes (KDIGO) guidelines for urine albumin/creatinine. This highlights the need for every clinical laboratory to assess the detection limits of their assays, including for lesser-discussed parameters such as UCr. Indeed, the error we reported here may affect other urine assays performing systematic urine pre-dilution and could have significant repercussions on the clinical management of patients.

Usual transaminase values: should they be reviewed and adjusted? / Valeurs usuelles des transaminases : faut-il les réexaminer et les adapter ?

Alanine (ALT) and aspartate aminotransferases (AST) are intracellular enzymes involved in the metabolism of amino acids. The measurements of their activities are two of the most ordered tests in clinical laboratories, used to screen, diagnose and follow diseases affecting the liver. Recent works highlighted that reference values for ALT and AST vary according to the analytical method and the individual's characteristics, like with many other biomarkers. Reference values for ALT show clinically significant differences according to the analytical method (higher when supplementing samples with phosphate pyridoxal), gender (higher in males than in females), body mass index (positive correlation), and age (higher in infants and the elderly), but not according to ethnicity or employed analyzer. According to the analytical method and age, reported reference values for AST show clinically significant differences, similar to ALT. These observations prove clinical laboratories' interest in updating their reference values according to sex, body mass index, age (especially when providing testing to pediatric or elderly populations), and the analytical method employed. If possible, a standardized method should be used, including sample supplementation with pyridoxal phosphate, to ensure the comparability of results between laboratories.

L'aspartate aminotransférase (ASAT) et l'alanine aminotransférase (ALAT) sont des enzymes intracellulaires impliquées dans le métabolisme des acides aminés. La mesure de leurs activités fait partie des examens biochimiques les plus couramment réalisés en pratique clinique, en particulier pour le dépistage, le diagnostic et le suivi des pathologies hépatiques. Les valeurs de référence de l'ALAT et de l'ASAT varient en fonction des caractéristiques individuelles et de la méthode d'analyse. Dans cet article, nous proposons une brève revue de ces sources de variations pour répondre à la question suivante : faut-il réexaminer et adapter les valeurs usuelles des transaminases ? Les valeurs usuelles rapportées pour l'ALAT montrent des différences cliniquement significatives selon la méthode analytique (plus élevées lors de l'emploi de phosphate pyridoxal), le sexe (plus élevées chez l'homme que chez la femme), l'indice de masse corporelle (corrélation positive) et l'âge (plus élevées chez les nourrissons et les personnes âgées). Ces études ne montrent pas de différences en fonction de l'origine ethnique ou de l'analyseur employé. Concernant l'ASAT, les valeurs usuelles rapportées montrent des différences cliniquement significatives selon la méthode analytique et l'âge, similaires à celles observées pour l'ALAT. Une méthode standardisée doit être utilisée de préférence, intégrant notamment l'emploi de phosphate de pyridoxal, pour assurer la comparabilité des résultats entre les laboratoires. Ces observations prouvent la nécessité pour les laboratoires cliniques d'actualiser leurs valeurs usuelles en fonction du sexe, de l'indice de masse corporelle, de l'âge (notamment pour les âges extrêmes : populations pédiatriques ou âgées) et de la méthode analytique employée.

SLC37A4-CDG: New biochemical insights for an emerging congenital disorder of glycosylation with major coagulopathy.

SLC37A4-CDG is an emerging congenital disorder of glycosylation which is characterized by a dominant inheritance and a major coagulopathy originating from the liver. Recent studies took interest in the biochemical alterations found in this CDG and showed that they consisted of multiple glycosylation abnormalities, which result from mislocalization of the endoplasmic reticulum glucose-6-phosphate transporter and associated Golgi homeostasis defects. In this work, we highlight in six affected individuals abnormal patterns for various serum N-glycoproteins and bikunin proteoglycan isoforms, together with specific alterations of the mass spectra of endoglycosidase H-released serum N-glycans. Collectively, these data complement previous findings, help to better delineate SLC37A4-CDG and could present interest in diagnosing this disease.