Hydroxychloroquine administration exacerbates acute kidney injury complicated by lupus nephritis.

BACKGROUND: Hydroxychloroquine (HCQ) has been recommended as a basic treatment for lupus nephritis (LN) during this decade based on its ability to improve LN-related renal immune-mediated inflammatory lesions. As a classical lysosomal inhibitor, HCQ may inhibit lysosomal degradation and disrupt protective autophagy in proximal tubular epithelial cells (PTECs). Therefore, the final renal effects of HCQ on LN need to be clarified. METHOD: HCQ was administered on spontaneous female MRL/lpr LN mice with severe proteinuria daily for 4 weeks. Moreover, the MRL/lpr mice with proteinuric LN were subjected to cisplatin-induced or unilateral ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) after 2 weeks of HCQ preadministration. RESULTS: As expected, HCQ treatment increased the survival ratio and downregulated the levels of serum creatinine in the mice with LN, ameliorated renal lesions, and inhibited renal interstitial inflammation. Unexpectedly, HCQ preadministration significantly increased susceptibility to and delayed the recovery of AKI complicated by LN, as demonstrated by an increase in PTEC apoptosis and expression of the tubular injury marker KIM-1 as well as the retardation of PTEC replenishment. HCQ preadministration suppressed the proliferation of PTECs by arresting cells in G1/S phase and upregulated the expression of cell cycle inhibitors. Furthermore, HCQ preadministration disrupted the PTEC autophagy-lysosomal pathway and accelerated PTEC senescence. CONCLUSION: HCQ treatment may increase susceptibility and delay the recovery of AKI complicated by LN despite its ability to improve LN-related renal immune-mediated inflammatory lesions. The probable mechanism involves accelerated apoptosis and inhibited proliferation of PTECs via autophagy-lysosomal pathway disruption and senescence promotion.

Advances, challenges and opportunities of phylogenetic and social network analysis using COVID-19 data.

Coronavirus disease 2019 (COVID-19) has attracted research interests from all fields. Phylogenetic and social network analyses based on connectivity between either COVID-19 patients or geographic regions and similarity between syndrome coronavirus 2 (SARS-CoV-2) sequences provide unique angles to answer public health and pharmaco-biological questions such as relationships between various SARS-CoV-2 mutants, the transmission pathways in a community and the effectiveness of prevention policies. This paper serves as a systematic review of current phylogenetic and social network analyses with applications in COVID-19 research. Challenges in current phylogenetic network analysis on SARS-CoV-2 such as unreliable inferences, sampling bias and batch effects are discussed as well as potential solutions. Social network analysis combined with epidemiology models helps to identify key transmission characteristics and measure the effectiveness of prevention and control strategies. Finally, future new directions of network analysis motivated by COVID-19 data are summarized.

Cumulative oxygen deficit is a novel predictor for the timing of invasive mechanical ventilation in COVID-19 patients with respiratory distress.

BACKGROUND AND OBJECTIVES: The timing of invasive mechanical ventilation (IMV) is controversial in COVID-19 patients with acute respiratory hypoxemia. The study aimed to develop a novel predictor called cumulative oxygen deficit (COD) for the risk stratification. METHODS: The study was conducted in four designated hospitals for treating COVID-19 patients in Jingmen, Wuhan, from January to March 2020. COD was defined to account for both the magnitude and duration of hypoxemia. A higher value of COD indicated more oxygen deficit. The predictive performance of COD was calculated in multivariable Cox regression models. RESULTS: A number of 111 patients including 80 in the non-IMV group and 31 in the IMV group were included. Patients with IMV had substantially lower PaO2 (62 (49, 89) vs. 90.5 (68, 125.25) mmHg; p < 0.001), and higher COD (-6.87 (-29.36, 52.38) vs. -231.68 (-1040.78, 119.83) mmHg·day) than patients without IMV. As compared to patients with COD < 0, patients with COD > 30 mmHg·day had higher risk of fatality (HR: 3.79, 95% CI [2.57-16.93]; p = 0.037), and those with COD > 50 mmHg·day were 10 times more likely to die (HR: 10.45, 95% CI [1.28-85.37]; p = 0.029). CONCLUSIONS: The study developed a novel predictor COD which considered both magnitude and duration of hypoxemia, to assist risk stratification of COVID-19 patients with acute respiratory distress.

Lung Mechanics of Mechanically Ventilated Patients With COVID-19: Analytics With High-Granularity Ventilator Waveform Data.

Background: Lung mechanics during invasive mechanical ventilation (IMV) for both prognostic and therapeutic implications; however, the full trajectory lung mechanics has never been described for novel coronavirus disease 2019 (COVID-19) patients requiring IMV. The study aimed to describe the full trajectory of lung mechanics of mechanically ventilated COVID-19 patients. The clinical and ventilator setting that can influence patient-ventilator asynchrony (PVA) and compliance were explored. Post-extubation spirometry test was performed to assess the pulmonary function after COVID-19 induced ARDS. Methods: This was a retrospective study conducted in a tertiary care hospital. All patients with IMV due to COVID-19 induced ARDS were included. High-granularity ventilator waveforms were analyzed with deep learning algorithm to obtain PVAs. Asynchrony index (AI) was calculated as the number of asynchronous events divided by the number of ventilator cycles and wasted efforts. Mortality was recorded as the vital status on hospital discharge. Results: A total of 3,923,450 respiratory cycles in 2,778 h were analyzed (average: 24 cycles/min) for seven patients. Higher plateau pressure (Coefficient: -0.90; 95% CI: -1.02 to -0.78) and neuromuscular blockades (Coefficient: -6.54; 95% CI: -9.92 to -3.16) were associated with lower AI. Survivors showed increasing compliance over time, whereas non-survivors showed persistently low compliance. Recruitment maneuver was not able to improve lung compliance. Patients were on supine position in 1,422 h (51%), followed by prone positioning (499 h, 18%), left positioning (453 h, 16%), and right positioning (404 h, 15%). As compared with supine positioning, prone positioning was associated with 2.31 ml/cmH2O (95% CI: 1.75 to 2.86; p < 0.001) increase in lung compliance. Spirometry tests showed that pulmonary functions were reduced to one third of the predicted values after extubation. Conclusions: The study for the first time described full trajectory of lung mechanics of patients with COVID-19. The result showed that prone positioning was associated with improved compliance; higher plateau pressure and use of neuromuscular blockades were associated with lower risk of AI.