Synergistic effect of elevated glucose levels with SARS-CoV-2 spike protein induced NOX-dependent ROS production in endothelial cells.

BACKGROUND: Diabetic patients infected with coronavirus disease 2019 (COVID-19) often have a higher probability of organ failure and mortality. The potential cellular mechanisms through which blood glucose exacerbates tissue damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. METHODS AND RESULTS: We cultured endothelial cells within differing glucose mediums with an increasing concentration gradient of SARS-CoV-2 Spike protein (S protein). S protein can cause the reduction of ACE2 and TMPRSS2, and activation of NOX2 and NOX4. A high glucose medium was shown to aggravate the decrease of ACE2 and activation of NOX2 and NOX4 in cultured cells, but had no effect on TMPRSS2. S protein mediated activation of the ACE2-NOX axis induced oxidative stress and apoptosis within endothelial cells, leading to cellular dysfunction via the reduction of NO and tight junction proteins which may collectively be exacerbated by elevated glucose. In addition, the glucose variability model demonstrated activation of the ACE2-NOX axis in a similar manner observed in the high glucose model in vitro. CONCLUSIONS: Our present study provides evidence for a mechanism through which hyperglycemia aggravates endothelial cell injury resulting from S protein mediated activation of the ACE2-NOX axis. Our research thus highlights the importance of strict monitoring and control of blood glucose levels within the context of COVID-19 treatment to potentially improve clinical outcomes.

Clinical Characteristics and Risk Factors for Acute Kidney Injury in COVID-19

Objective: The objective of the study is to describe the clinical characteristics, risk factors, and prognosis for acute kidney injury (AKI) among patients with coronavirus disease (COVID-19). Methods: Retrospective study of 456 consecutive patients with confirmed COVID-19 infection at the whole hospital from January 1 to March 1, 2020 was enrolled. Demographic, clinical characteristics, the risk factors, and prognosis were collected and analyzed. Results: Of 456 patients with COVID-19, 38 patients developed AKI. Patients with AKI were older and predominantly male sex and were more likely to have comorbidities such as hypertension, cardiovascular, and cerebrovascular diseases. Among patients with AKI, the white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, alanine aminotransferase, and C-reaction protein were increased, and lymphocyte and platelet count were decreased. Multivariate analysis showed that age, hypertension, and lymphocyte count were independent risk factors for AKI. The overall mortality rate of 456 patients was 9.9%, and the mortality rate of patients with AKI was 23.7%. In particular, increasing AKI severity was associated with increased risk. Conclusions: The risk of AKI was high in patients with COVID-19. Older age, hypertension, and lower lymphocyte count were independent risk factors for AKI. COVID-19-associated AKI was associated with higher risk of death in patients with COVID-19.

Differential Effects of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on COVID-19

Background: The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) on the coronavirus disease 2019 (COVID-19) remains controversial from clinic evidence. Objectives: The objectives of this study were to report the major characteristics and clinical outcomes of COVID-19 patients treated with ACEIs and ARBs and compare the different effects of the two drugs for outcomes of COVID-19 patients. Methods: This is a retrospective, two-center case series of 198 consecutive COVID-19 patients with a history of hypertension. Results: Among 198 patients, 58 (29.3%) and 16 (8.1%) were on ARB and ACEI, respectively. Patients who were on ARB or ACEI/ARB had a significantly lower rate of severe illness and acute respiratory distress syndrome (ARDS) when compared with patients treated with ACEI alone or not receiving RAAS blocker (P < 0.05). The Kaplan–Meier survival curve showed that patients with ARB in their antihypertensive regimen had a trend toward a higher survival rate when compared with individuals without ARB (adjusted hazard ratio, 0.27;95% confidence interval [CI], 0.07–1.02;P = 0.054). The occurrence rates of severe illness, ARDS, and death were similar in the two groups regardless of receiving ACEI. The Cox regression analyses showed a better survival in the ARB group than the ACEI group (adjusted hazard ratio, 0.03;95% CI, 0.00–0.58;P = 0.02). Conclusions: Our data may provide that some evidence of using ARB, but not ACEI, was associated with a reduced rate of severe illness and ARDS, indicating their potential protective impact in COVID-19. Further large sample sizes and multiethnic populations are warranted to confirm our findings.

Clinical Characteristics and Risk Factors of Liver Dysfunction in COVID-19 Patients

Background: COVID-19 outbreak has spread around the world. Liver dysfunction (LD) was related with high mortality in COVID-19. Methods: Retrospective, single-center study case series of 425 consecutive hospitalized COVID-19 patients were enrolled. Demographic, clinical, laboratory, and treatment data were collected. Results: A total of 425 patients were included in this study, 145 of whom had LD. The overall mortality rate was 8.9%, while 17.9% in the LD group and 4.3% in the nonliver dysfunction (NLD) group. Age, sex, and hypertension were the independent risk factors of LD. LD was an independent risk factor for incidence of severe illness, acute respiratory distress syndrome, and death. The survival rate of patients in LD group was lower than that in NLD group (P < 0.001). A similar trend was observed by the multivariate regression analysis (adjusted hazard ratio, 3.52;95% confidence interval [CI], 1.69–7.33;P = 0.001). Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers had effect to reduce LD (odds ratio of 0.48 [95% CI, 0.232–0.989;P = 0.045]). Conclusions: LD is one of the main features of hospitalized patients of COVID-19, with a worse prognosis. Patients of COVID-19 with LD on admission should be more cautions.