Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Objectives Talaromycosis is an invasive mycosis endemic to Southeast Asia. This study aimed to investigate the epidemiology, clinical features and prognostic factors of HIV‐associated talaromycosis in Guangdong, China. Methods We retrospectively evaluated HIV patients hospitalized with histopathology‐ or culture‐confirmed talaromycosis between 2011 and 2017. Factors associated with poor prognosis were identified using logistic regression. Results Overall, 1079 patients with HIV‐associated talaromycosis were evaluated. Both the number and prevalence of talaromycosis among HIV admissions increased from 125 and 15.7% in 2011 to 253 and 18.8% in 2017, respectively, reflecting the increase in HIV admissions. Annual admissions peaked during the rainy season between March and August. Common clinical manifestations included fever (85.6%), peripheral lymphadenopathy (72.3%), respiratory symptoms (60.8%), weight loss (49.8%), skin lesions (44.5%) and gastrointestinal symptoms (44.3%). Common laboratory abnormalities were hypoalbuminaemia (98.6%), anaemia (95.6%), elevated aspartate aminotransferase level (AST) (76.9%), elevated alkaline phosphatase level (55.8%) and thrombocytopenia (53.7%). The median CD4 count was 9 cells/μL. Talaromyces marneffei was isolated from blood and bone marrow cultures of 66.6% and 74.5% of patients, respectively. The rate increased to 86.6% when both cultures were performed concurrently. At discharge, 14% of patients showed worsening conditions or died. Leucocytosis, thrombocytopenia, elevated AST, total bilirubin, creatinine and azole monotherapy independently predicted poor prognosis. Conclusions The incidence of HIV‐associated talaromycosis has increased in Guangdong with the high HIV burden in China. Skin lesions were seen in less than half of patients. Induction therapy with azole alone is associated with higher mortality. Findings from this study should help to improve treatment of the disease.

Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with Talaromyces marneffei (TSM group, n = 93) and those without Talaromyces marneffei (non-TSM group, n = 190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4? counts of \ 50 cells/lL compared to those with CD4? counts ranged from 50-100 cells/lL. The Mp1p EIA has the advantage of assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4? counts.