Highlights d Statin treatment among 13,981 patients with COVID-19 was retrospectively studied d Statin use in this cohort was associated with a lower risk of all-cause mortality d Adding an ACE inhibitor or an ARB did not affect statinassociated outcome in the cohort d The benefit of statins among this cohort may be due to immunomodulatory benefits

Ferroptosis is a recently identified iron‐dependent form of nonapoptotic cell death implicated in brain, kidney, and heart pathology. However, the biological roles of iron and iron metabolism in ferroptosis remain poorly understood. Here, we studied the functional role of iron and iron metabolism in the pathogenesis of ferroptosis. We found that ferric citrate potently induces ferroptosis in murine primary hepatocytes and bone marrow–derived macrophages. Next, we screened for ferroptosis in mice fed a high‐iron diet and in mouse models of hereditary hemochromatosis with iron overload. We found that ferroptosis occurred in mice fed a high‐iron diet and in two knockout mouse lines that develop severe iron overload (Hjv–/– and Smad4Alb/Alb mice) but not in a third line that develops only mild iron overload (Hfe –/– mice). Moreover, we found that iron overload–induced liver damage was rescued by the ferroptosis inhibitor ferrostatin‐1. To identify the genes involved in iron‐induced ferroptosis, we performed microarray analyses of iron‐treated bone marrow–derived macrophages. Interestingly, solute carrier family 7, member 11 (Slc7a11), a known ferroptosis‐related gene, was significantly up‐regulated in iron‐treated cells compared with untreated cells. However, genetically deleting Slc7a11 expression was not sufficient to induce ferroptosis in mice. Next, we studied iron‐treated hepatocytes and bone marrow–derived macrophages isolated from Slc7a11–/– mice fed a high‐iron diet. Conclusion: We found that iron treatment induced ferroptosis in Slc7a11–/– cells, indicating that deleting Slc7a11 facilitates the onset of ferroptosis specifically under high‐iron conditions; these results provide compelling evidence that iron plays a key role in triggering Slc7a11‐mediated ferroptosis and suggest that ferroptosis may be a promising target for treating hemochromatosis‐related tissue damage. (Hepatology 2017;66:449–465).

Background The global numbers of confirmed cases and deceased critically ill patients with COVID-19 are increasing. However, the clinical course, and the 60-day mortality and its predictors in critically ill patients have not been fully elucidated. The aim of this study is to identify the clinical course, and 60-day mortality and its predictors in critically ill patients with COVID-19. Methods Critically ill adult patients admitted to intensive care units (ICUs) from 3 hospitals in Wuhan, China, were included. Data on demographic information, preexisting comorbidities, laboratory findings at ICU admission, treatments, clinical outcomes, and results of SARS-CoV-2 RNA tests and of serum SARS-CoV-2 IgM were collected including the duration between symptom onset and negative conversion of SARS-CoV-2 RNA. Results Of 1748 patients with COVID-19, 239 (13.7%) critically ill patients were included. Complications included acute respiratory distress syndrome (ARDS) in 164 (68.6%) patients, coagulopathy in 150 (62.7%) patients, acute cardiac injury in 103 (43.1%) patients, and acute kidney injury (AKI) in 119 (49.8%) patients, which occurred 15.5 days, 17 days, 18.5 days, and 19 days after the symptom onset, respectively. The median duration of the negative conversion of SARS-CoV-2 RNA was 30 (range 6–81) days in 49 critically ill survivors that were identified. A total of 147 (61.5%) patients deceased by 60 days after ICU admission. The median duration between ICU admission and decease was 12 (range 3–36). Cox proportional-hazards regression analysis revealed that age older than 65 years, thrombocytopenia at ICU admission, ARDS, and AKI independently predicted the 60-day mortality. Conclusions Severe complications are common and the 60-day mortality of critically ill patients with COVID-19 is considerably high. The duration of the negative conversion of SARS-CoV-2 RNA and its association with the severity of critically ill patients with COVID-19 should be seriously considered and further studied.

Baricitinib therapy in COVID-19: A pilot study on safety and clinical impactDear Editor , 38.1 (37.7-38.7) 0.356 Breath rate N/min, median (IQR), 23 (19.5-24.2) 22 (19.7-24) 0.665 SpO2 (%),median (IQR) 91 (90-92.5) 92 (91.2-93) 0.157 PaO2/FiO2, median (IQR) 290 (199.2-292.2) 268.6 (264.4-295) 0.603 Pulse rate, median (IQR) 82 (73-88.3) 90 (87.2-94.5) 0.069 SBP mm/Hg, median (IQR) 120 (110-131.2) 105 (100-111.25) 0.003 DBP mm/Hg, median (IQR) 70 (60-80) 62.5 (60-66.25) 0.094 WBC (x10 9 /L), median (IQR) 7.8 (5.8-10.8) 8.2 (7.3-8.8) 0.908 Neutrophils (x10 9 /L), median (IQR) 6,5 (4.5-7.7) 6.9 (6.4-7.6) 0.707 Lymphocytes (x10 9 /L), median (IQR) 0.7 (0.7-1.2) 0.89 (0.7-0.9) 1.0 0 0 Hemoglobin (g/L), median (IQR) 118 (102-134.2) 125 (108-134) 0.568 Platelets (x10 9 /L), median (IQR) 203 (174-227) 366 (340-407) 0.0 0 0 ALT (U/L), median (IQR) 28.5 (23.5-52) 44 (37-50) 0.157 AST (U/L), median (IQR) 34 (26.2-48) 44 (34.7-47) 0.525 Creatinine (mg/dl), median (IQR)1.0 (0.9-1.1) 1.00 (0.9-1) 0.583 CRP (mg/dl), median (IQR) 8.2 (5.8-14.5) 3 (1.5-3.2) 0.002 Procalcitonin ng/ml, median (IQR) 0.7 (0.4-1.1) 1.2 (0.8-2.1) 0.902 MEWS, median (IQR) 3 ( 2-3.25) 3 (3-4) 0.544 Abbreviations and symbols: N = number;% = percentage; °C: grade Celsius; min = minute; SpO2 = peripheral capillary oxygen saturation; PaO2/FiO2 = ratio of arterial oxygen partial pressure to fractional inspired oxygen; SBP = systolic blood pressure; DBP = diastolic blood pressure; WBC = white blood cells; AST = serum glutamic oxaloacetic transaminase; ALT = serum alanine aminotransferase; MEWS = Modified Early Warning Score; IQR: Interquartile range.