In December 2019, a cluster of acute respiratory illness, now known as novel coronavirus–infected pneumonia (NCIP), occurred in Wuhan, Hubei Province, China.^1-5 The disease has rapidly spread from Wuhan to other areas. As of January 31, 2020, a total of 9692 NCIP cases in China have been confirmed. Internationally, cases have been reported in 24 countries and 5 continents.⁶ On January 3, 2020, the 2019 novel coronavirus (2019-nCoV) was identified in samples of bronchoalveolar lavage fluid from a patient in Wuhan and was confirmed as the cause of the NCIP.⁷ Full-genome sequencing and phylogenic analysis indicated that 2019-nCoV is a distinct clade from the betacoronaviruses associated with human severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).⁷ The 2019-nCoV has features typical of the coronavirus family and was classified in the betacoronavirus 2b lineage. The 2019-nCoV has close similarity to bat coronaviruses, and it has been postulated that bats are the primary source. While the origin of the 2019-nCoV is still being investigated, current evidence suggests spread to humans occurred via transmission from wild animals illegally sold in the Huanan Seafood Wholesale Market.⁸

Reactive oxygen species- (ROS-) induced lipid peroxidation plays a critical role in cell death including apoptosis, autophagy, and ferroptosis. This fundamental and conserved mechanism is based on an excess of ROS which attacks biomembranes, propagates lipid peroxidation chain reactions, and subsequently induces different types of cell death. A highly evolved sophisticated antioxidant system exists that acts to protect the cells from oxidative damage. In this review, we discussed how ROS propagate lipid peroxidation chain reactions and how the products of lipid peroxidation initiate apoptosis and autophagy in current models. We also discussed the mechanism of lipid peroxidation during ferroptosis, and we summarized lipid peroxidation in pathological conditions of critical illness. We aim to bring a more global and integrative sight to know how different ROS-induced lipid peroxidation occurs among apoptosis, autophagy, and ferroptosis.

Mitophagy is an essential mitochondrial quality control mechanism that eliminates damaged mitochondria and the production of reactive oxygen species (ROS). The relationship between mitochondria oxidative stress, ROS production and mitophagy are intimately interwoven, and these processes are all involved in various pathological conditions of acute kidney injury (AKI). The elimination of damaged mitochondria through mitophagy in mammals is a complicated process which involves several pathways. Furthermore, the interplay between mitophagy and different types of cell death, such as apoptosis, pyroptosis and ferroptosis in kidney injury is unclear. Here we will review recent advances in our understanding of the relationship between ROS and mitophagy, the different mitophagy pathways, the relationship between mitophagy and cell death, and the relevance of these processes in the pathogenesis of AKI. Abbreviations: AKI: acute kidney injury; AMBRA1: autophagy and beclin 1 regulator 1; ATP: adenosine triphosphate; BAK1: BCL2 antagonist/killer 1; BAX: BCL2 associated X, apoptosis regulator; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BH3: BCL2 homology domain 3; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CASP1: caspase 1; CAT: catalase; CCCP: carbonyl cyanide m-chlorophenylhydrazone; CI-AKI: contrast-induced acute kidney injury; CISD1: CDGSH iron sulfur domain 1; CL: cardiolipin; CNP: 2’,3’-cyclic nucleotide 3’-phosphodiesterase; DNM1L/DRP1: dynamin 1 like; E3: enzyme 3; ETC: electron transport chain; FA: folic acid; FUNDC1: FUN14 domain containing 1; G3P: glycerol-3-phosphate; G6PD: glucose-6-phosphate dehydrogenase; GPX: glutathione peroxidase; GSH: glutathione; GSK3B: glycogen synthase kinase 3 beta; GSR: glutathione-disulfide reductase; HIF1A: hypoxia inducible factor 1 subunit alpha; HUWE1: HECT, UBA and WWE domain containing 1; IL1B: interleukin 1 beta; IMM: inner mitochondrial membrane; IPC: ischemic preconditioning; IRI: ischemia-reperfusion injury; LIR: LC3-interacting region; LPS: lipopolysaccharide; MA: malate-aspartate; MPT: mitochondrial permeability transition; MUL1: mitochondrial E3 ubiquitin protein ligase 1; mtROS: mitochondrial ROS; NLR: NOD-like receptor; NLRP3: NLR family pyrin domain containing 3; NOX: NADPH oxidase; OGD-R: oxygen-glucose deprivation-reperfusion; OMM: outer mitochondrial membrane; OPA1: OPA1 mitochondrial dynamin like GTPase; OXPHOS: oxidative phosphorylation; PARL: presenilin associated rhomboid like; PINK1: PTEN induced kinase 1; PLSCR3: phospholipid scramblase 3; PMP: peptidase, mitochondrial processing; PRDX: peroxiredoxin; PRKN: parkin RBR E3 ubiquitin protein ligase; RPTC: rat proximal tubular cells; ROS: reactive oxygen species; SLC7A11/xCT: solute carrier family 7 member 11; SOD: superoxide dismutase; SOR: superoxide reductase; SQSTM1/p62: sequestosome 1; TCA: tricarboxylic acid; TIMM: translocase of inner mitochondrial membrane; TOMM: translocase of outer mitochondrial membrane; TXN: thioredoxin; VDAC: voltage dependent anion channel; VCP: valosin containing protein.

OBJECTIVE Diabetes is common in COVID-19 patients and associated with unfavorable outcomes. We aimed to describe the characteristics and outcomes and to analyze the risk factors for in-hospital mortality of COVID-19 patients with diabetes. RESEARCH DESIGN AND METHODS This two-center retrospective study was performed at two tertiary hospitals in Wuhan, China. Confirmed COVID-19 patients with diabetes (N = 153) who were discharged or died from 1 January 2020 to 8 March 2020 were identified. One sex- and age-matched COVID-19 patient without diabetes was randomly selected for each patient with diabetes. Demographic, clinical, and laboratory data were abstracted. Cox proportional hazards regression analyses were performed to identify the risk factors associated with the mortality in these patients. RESULTS Of 1,561 COVID-19 patients, 153 (9.8%) had diabetes, with a median age of 64.0 (interquartile range 56.0–72.0) years. A higher proportion of intensive care unit admission (17.6% vs. 7.8%, P = 0.01) and more fatal cases (20.3% vs. 10.5%, P = 0.017) were identified in COVID-19 patients with diabetes than in the matched patients. Multivariable Cox regression analyses of these 306 patients showed that hypertension (hazard ratio [HR] 2.50, 95% CI 1.30–4.78), cardiovascular disease (HR 2.24, 95% CI 1.19–4.23), and chronic pulmonary disease (HR 2.51, 95% CI 1.07–5.90) were independently associated with in-hospital death. Diabetes (HR 1.58, 95% CI 0.84–2.99) was not statistically significantly associated with in-hospital death after adjustment. Among patients with diabetes, nonsurvivors were older (76.0 vs. 63.0 years), most were male (71.0% vs. 29.0%), and they were more likely to have underlying hypertension (83.9% vs. 50.0%) and cardiovascular disease (45.2% vs. 14.8%) (all P values <0.05). Age ≥70 years (HR 2.39, 95% CI 1.03–5.56) and hypertension (HR 3.10, 95% CI 1.14–8.44) were independent risk factors for in-hospital death of patients with diabetes. CONCLUSIONS COVID-19 patients with diabetes had worse outcomes compared with the sex- and age-matched patients without diabetes. Older age and comorbid hypertension independently contributed to in-hospital death of patients with diabetes.

Background: In December 2019, coronavirus disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. Methods: Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan and Xishui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic, and clinical data were collected. The clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. Results: A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia, and radiological multi-lobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury, and adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough, and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia, and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome, refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia, and death. Older age and male sex were independent risk factors for poor outcome of the illness. Conclusions: A period of 7–13 days after illness onset is the critical stage in the COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.