Ziwei Hu

BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.

BACKGROUND AND PURPOSE: Information on stroke survivors infected with coronavirus disease 2019 (COVID-19) is limited. The aim of this study was to describe specific clinical characteristics and outcomes of patients with COVID-19 with a history of stroke. METHODS: All the confirmed cases of COVID-19 at Tongji Hospital from January 27 to March 5, 2020, were included in our cohort study. Clinical data were analyzed and compared between patients with and without a history of stroke. RESULTS: Of the included 1875 patients with COVID-19, 50 patients had a history of stroke. The COVID-19 patients with medical history of stroke were older with more comorbidities, had higher neutrophil count, and lower lymphocyte and platelet counts than those without history of stroke. The levels of D-dimers, cardiac troponin I, NT pro-brain natriuretic peptide, and interleukin-6 were also markedly higher in patients with history of stroke. Stroke survivors who underwent COVID-19 developed more acute respiratory distress syndrome and received more noninvasive mechanical ventilation. Data from propensity-matched analysis indicated a higher proportion of patients with COVD-19 with a history of stroke were admitted to the intensive care unit requiring mechanical ventilation and were more likely to be held in the unit or die, compared with non-stroke history COVID-19 patients. CONCLUSIONS: Patients with COVID-19 with a history of stroke had more severe clinical symptoms and poorer outcomes compared with those without a history of stroke.

Microglia play a critical role in the clearance of myelin debris, thereby ensuring functional recovery from neural injury. Here, using mouse model of demyelination following two-point LPC injection, we show that the microglial autophagic-lysosomal pathway becomes overactivated in response to severe demyelination, leading to lipid droplet accumulation and a dysfunctional and pro-inflammatory microglial state, and finally failed myelin debris clearance and spatial learning deficits. Data from genetic approaches and pharmacological modulations, via microglial Atg5 deficient mice and intraventricular BAF A1 administration, respectively, demonstrate that staged suppression of excessive autophagic-lysosomal activation in microglia, but not sustained inhibition, results in better myelin debris degradation and exerts protective effects against demyelination. Combined multi-omics results in vitro further showed that enhanced lipid metabolism, especially the activation of the linoleic acid pathway, underlies this protective effect. Supplementation with conjugated linoleic acid (CLA), both in vivo and in vitro, could mimic these effects, including attenuating inflammation and restoring microglial pro-regenerative properties, finally resulting in better recovery from demyelination injuries and improved spatial learning function, by activating the peroxisome proliferator-activated receptor (PPAR-γ) pathway. Therefore, we propose that pharmacological inhibition targeting microglial autophagic-lysosomal overactivation or supplementation with CLA could represent a potential therapeutic strategy in demyelinated disorders.

In recent decades, infections caused by the opportunistic fungus Candida albicans have increased, especially in patients with immunodeficiency. In this study, we investigated the mechanism of action of sanguinarine (SAN) against C. albicans both in vitro and in vivo . SAN exhibited antifungal activity against C. albicans clinical isolates, with MICs in the range of 112.8–150.5 μM. Furthermore, scanning electron and transmission electron microscopy showed that SAN induced morphological changes as well as structure disruption in C. albicans cells, including masses of cellular debris, ruptured cell walls, and membrane deformation. Flow cytometry revealed that SAN could lead to cell membrane damage, and ergosterol content analysis indicated that SAN could cause ergosterol content reduction exceeding 90%. Further, we validated the efficacy of SAN against candidiasis caused by C. albicans in a murine model, and SAN significantly improved survival and reduced weight loss compared to vehicle. The treatment of 1.5 and 2.5 mg/kg/d SAN obviously reduced the fungal burden in the kidney. In addition, histopathological examination indicated that no fungal cells were observed in lung and kidney tissues after SAN treatment. Hence, this study suggests that SAN is a promising plant-derived compound for the development of an effective anticandidal agent.