Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), − 4.08 g/L (95% CI − 5.12; − 3.05)] and red blood cell count [WMD, − 0.16 × 1012 /L (95% CI − 0.31; − 0.014)], and higher ferritin [WMD, − 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.

The potential role of branched-chain amino acids (BCAAs) in the pathogenesis of cardiometabolic diseases is increasingly recognized, but the association of BCAAs with incident hypertension remains unknown. The aim of the present study was to explore the association of BCAAs with incident hypertension in a prospective population-based cohort study. We measured plasma concentrations of BCAAs by means of nuclear magnetic resonance spectroscopy in 4169 participants from the PREVEND (Prevention of Renal and Vascular End-stage Disease) study. We estimated the risk of incident hypertension using multivariable-adjusted Cox regression models. After a median follow-up of 8.6 years, incident hypertension was ascertained in 924 subjects. Cox regression analyses revealed a significant association between BCAAs and incident hypertension. The hazard ratio per one SD of BCAAs was 1.11 (95% CI, 1.02–1.20; P =0.01) after full adjustment for multiple clinical variables. Likewise, the fully adjusted association remained significant when evaluated as categorical variable (hazard ratio for upper quartile with lowest quartile as reference category, 1.36; 95% CI, 1.11–1.68; P =0.003). Furthermore, the net reclassification improvement assessment improved after addition of BCAAs to a traditional risk model ( P <0.001). This prospective study revealed that high plasma concentrations of BCAAs are associated with an increased risk of newly developed hypertension. The association remained after adjusting for age, sex, body mass index, and lipid profile.

IMPORTANCEHigher plasma concentrations of vitamin B 12 have been associated with mortality in elderly and hospitalized populations, including patients with chronic kidney disease, but the association of plasma concentrations of vitamin B 12 with mortality in the general population remains unclear. OBJECTIVE To investigate the association of plasma concentrations of vitamin B 12 with all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS This longitudinal cohort study used post hoc analysis to examine data from participants of the Prevention of Renal and Vascular End-stage Disease Study in Groningen, the Netherlands. Participants included individuals who completed the second screening visit beginning January 1, 2001, excluding those who were missing values of vitamin B 12 plasma concentrations or used vitamin B 12 supplementation. Follow-up time was defined between the beginning of the second screening round to end of follow-up on January 1, 2011. Data analysis was conducted from October 2, 2018, to February 22, 2019. EXPOSURES Plasma vitamin B 12 concentration level. MAIN OUTCOMES AND MEASURES Death as recorded by the Central Bureau of Statistics of Groningen, the Netherlands. RESULTS A total of 5571 participants (mean [SD] age, 53.5 [12.0] years; 2830 [50.8%] men) were included in analyses. Median (interquartile range) plasma concentration of vitamin B 12 was 394.42 (310.38-497.42) pg/mL. During the median (interquartile range) of 8.2 (7.7-8.9) years of follow-up, 226 participants (4.1%) died. According to quartiles of the distribution of plasma vitamin B 12 concentration levels, mortality rates were 33.8 deaths per 10 000 person-years for the quartile with the lowest plasma concentration of vitamin B 12 and 65.7 deaths per 10 000 person-years for the quartile with the highest plasma concentration of vitamin B 12 . After adjustment for multiple clinical and laboratory variables, Cox regression analyses found a significant association between higher vitamin B 12 plasma concentration level and increased risk of all-cause mortality (hazard ratio per 1-SD increase, 1.25 [95% CI, 1.06-1.47]; P = .006).CONCLUSIONS AND RELEVANCE These findings suggest that higher levels of plasma concentrations of vitamin B 12 were associated with increased risk of all-cause mortality after adjusting for age, sex, renal function, and other clinical and laboratory variables. The mechanisms underlying this association remain to be established.