Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that leads to severe respiratory failure (RF). It is known that host exposure to viral infection triggers an iron-lowering response to mitigate pathogenic load and tissue damage. However, the association between host iron-lowering response and COVID-19 severity is not clear. This two-center observational study of 136 adult hospitalized COVID-19 patients analyzed the association between disease severity and initial serum iron, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels. Serum iron levels were significantly lower in patients with mild RF than in the non-RF group; however, there were no significant differences in iron levels between the non-RF and severe RF groups, depicting a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron and TSAT levels were independently associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.

Serum cholinesterase associated with COVID-19 pneumonia severity and mortality Dear Editor, Kunutsor and Laukkanen have written to this journal regarding elevated admission levels of markers of liver injury (alanine aminotransferase and aspartate aminotransferase, gammaglutamyltransferase, alkaline phosphatase and total bilirubin) may be associated with progression to severe disease or death in COVID-19. 1 On the other hand, serum cholinesterase plays an important role in the inflammatory response and may be associated with prognosis in sepsis. 2-4 We focused on the similarities between severe COVID-19 pneumonia and sepsis. We examined associations between cholinesterase levels on admission and the severity, and mortality of patients with COVID-19 pneumonia, as well as the interaction between cholinesterase and the previously reported factors of severity and mortality. We included patients who had tested positive for severe acute respiratory syndrome coronavirus 2 from February to May 2020 at

AimCapillary refill time has been widely adopted for clinical assessment of the circulatory status of patients in emergency settings. We previously introduced quantitative capillary refill time and found a positive association between longer quantitative capillary refill time and higher lactate levels in the intensive care units, but not in the emergency department. In this study, we aimed to identify a quantitative and clinically applicable index of circulatory status (ΔA b) that can be measured with quantitative capillary refill time, then evaluated the linear association between this index and lactate levels in the emergency department.MethodsWe undertook a prospective single‐center observational study at a university hospital from November 2015 to July 2016. We included 139 patients with endogenous diseases to test the association between quantitative capillary refill time, ΔA b (measured with a pulse oximeter), and lactate levels.ResultsΔA b was independently and significantly associated with high lactate levels (odds ratio [95% confidence interval]: 0.16 [0.05–0.45]).ConclusionsWe introduced ΔA b, measured using quantitative capillary refill time, as a surrogate index of lactate levels to overcome the shortcomings of capillary refill time. We showed that ΔA b is a feasible, non‐invasive, and rapid assessment of patients with high lactate levels in emergency primary care settings. Future multicenter studies with a longitudinal design should be undertaken to verify our findings.

Background Coronavirus disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure is associated with high mortality. The pathogenesis of COVID-19 is associated with microembolism or microvascular endothelial injuries. Here, we report that syndecan-1 (SDC-1), a component of the endothelial glycocalyx, may be a biomarker of severity classification for COVID-19 related to endothelial injury. Methods and analysis We analyzed the data of COVID-19 patients for 1 year from February 2020 at Yokohama City University Hospital and Yokohama City University Medical Center Hospital. We selected COVID-19 patients who required admission care, including intensive care, and analyzed the classification of severe and critical COVID-19 retrospectively, using various clinical data and laboratory data with SDC-1 by ELISA. Results We analyzed clinical and laboratory data with SDC-1 in five severe COVID-19 and ten critical COVID-19 patients. In the two groups, their backgrounds were almost the same. In laboratory data, the LDH, CHE, and CRP levels showed significant differences in each group (P = 0.032, P < 0.0001, and P = 0.007, respectively) with no significant differences in coagulation-related factors (platelet, PT-INR, d-dimer, ISTH score; P = 0.200, 0.277, 0.655, and 0.36, respectively). For the clinical data, the SOFA score was significantly different from admission day to day 14 of admission (p < 0.0001). The SDC-1 levels of critical COVID-19 patients were significantly higher on admission day and all-time course compared with the levels of severe COVID-19 patients (P = 0.009 and P < 0.0001, respectively). Conclusions Temporal change of SDC-1 levels closely reflect the severity of COVID-19, therefore, SDC-1 may be a therapeutic target and a biomarker for the severity classification of Covid-19.

Objective: To evaluate the association between iron metabolism indicators and disease severity in hospitalized patients with coronavirus disease 2019 (COVID-19). Design: Two-center observational study Setting: A university hospital and a core hospital in Yokohama, Japan Patients: Adults with COVID-19 whose serum iron levels were measured within the first 5 days of hospitalization were included. Patients who refused mechanical ventilation were excluded from the study. Measurements and Main Results: One hundred thirty-six patients were included in this study. We analyzed the association between COVID-19 severity and serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) levels. Disease severity was defined as the worst respiratory status during hospitalization. Serum iron levels were significantly lower in patients with mild respiratory failure (RF) (n=55, median serum iron level: 24 [interquartile range: 19-42] mg/dL) than in the non-RF group (n=44, 40 [24-80] mg/dL) and the severe RF group (n=37, 60 [23.5-87] mg/dL); however, there were no significant differences in iron levels between the non-RF and severe RF groups (non-RF vs. mild RF: p=0.019, non-RF vs. severe RF: p>0.999, and mild RF vs. severe RF: p=0.009). That is, there was a U-shaped association between serum iron levels and disease severity. TIBC levels decreased significantly with increasing severity; consequently, TSAT was significantly higher in patients with severe RF than in other patients. Multivariate analysis including only patients with RF adjusted for age and sex demonstrated that higher serum iron or TSAT levels were independently associated with development of severe RF. Conclusions: A U-shaped association between serum iron level and RF severity in hospitalized COVID-19 patients was observed. Higher serum iron levels in COVID-19 patients with RF are associated with the development of severe RF, indicating that inadequate response to lower serum iron might be an exacerbating factor for COVID-19.