Maternal and infant outcomes in women with and without gestational diabetes mellitus in the COVID-19 era in China: Lessons learned

Aims The global COVID-19 pandemic has required a drastic transformation of prenatal care services. Whether the reformulation of the antenatal care systems affects maternal and infant outcomes remains unknown. Particularly, women with gestational diabetes mellitus (GDM) are among those who bear the greatest brunt. Thus, this study aimed to evaluate the impact of COVID-19 lockdown during late pregnancy on maternal and infant outcomes in women stratified by the GDM status in China. Study design The participants were women who experienced the COVID-19 lockdown during late pregnancy (3185 in the 2020 cohort) or not (2540 in the 2019 cohort) that were derived from the Beijing Birth Cohort Study. Maternal metabolic indicators, neonatal outcomes, and infant anthropometrics at 12 months of age were compared between the two cohorts, stratified by the GDM status. Results Participants who experienced COVID-19 lockdown in late pregnancy showed lower gestational weight gain than those in the control cohort. Nevertheless, they displayed a worse metabolic profile. COVID-19 lockdown during pregnancy was associated with higher glycosylated hemoglobin (HbA1c) (β= 0.11, 95% CI = 0.05–0.16, q-value = 0.002) and lower high density lipoprotein cholesterol level (HDL-C) level (β=–0.09, 95% CI = –0.14 to –0.04, q-value = 0.004) in women with GDM, adjusted for potential confounders. In normoglycemic women, COVID-19 lockdown in late pregnancy was associated with higher fasting glucose level (β= 0.10, 95% CI = 0.08–0.12, q-value <0.0001), lower HDL-C level (β=–0.07, 95% CI = –0.08 to –0.04, q-value <0.0001), and increased risk of pregnancy-induced hypertension (adjusted OR=1.80, 95%CI=1.30–2.50, q-value=0.001). The fasting glucose level decreased less from early to late pregnancy in women who experienced COVID-19 lockdown than in the controls, regardless of the GDM status. The HDL-C has risen less with COVID-19 lockdown in the normoglycemic subgroup. In contrast, no significant differences regarding neonatal outcomes or infant weight were found between the two cohorts. Conclusion Experiencing the COVID-19 lockdown in pregnancy was associated with worse maternal metabolic status but similar neonatal outcomes and infant weight.

Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.

Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide. In addition to respiratory symptoms, COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of antioxidant proteins, participating in COVID-19-mediated inflammation and liver injury. Here, we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury. Additionally, we describe some mechanisms and treatment strategies.

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS.

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.

Inhibition of drug-metabolizing enzymes by Qingfei Paidu decoction: Implication of herb-drug interactions in COVID-19 pharmacotherapy.

Corona Virus Disease 2019 (COVID-19) has spread all over the world and brings significantly negative effects on human health. To fight against COVID-19 in a more efficient way, drug-drug or drug-herb combinations are frequently used in clinical settings. The concomitant use of multiple medications may trigger clinically relevant drug/herb-drug interactions. This study aims to assay the inhibitory potentials of Qingfei Paidu decoction (QPD, a Chinese medicine compound formula recommended for combating COVID-19 in China) against human drug-metabolizing enzymes and to assess the pharmacokinetic interactions in vivo. The results demonstrated that QPD dose-dependently inhibited CYPs1A, 2A6, 2C8, 2C9, 2C19, 2D6 and 2E1 but inhibited CYP3A in a time- and NADPH-dependent manner. In vivo test showed that QPD prolonged the half-life of lopinavir (a CYP3A substrate-drug) by 1.40-fold and increased the AUC of lopinavir by 2.04-fold, when QPD (6 g/kg) was co-administrated with lopinavir (160 mg/kg) to rats. Further investigation revealed that Fructus Aurantii Immaturus (Zhishi) in QPD caused significant loss of CYP3A activity in NADPH-generating system. Collectively, our findings revealed that QPD potently inactivated CYP3A and significantly modulated the pharmacokinetics of CYP3A substrate-drugs, which would be very helpful for the patients and clinicians to avoid potential drug-interaction risks in COVID-19 treatment.

The efficacy and safety of Chinese traditional medicine injections on patients with coronavirus disease 2019: A protocol for systematic review and meta analysis.

INTRODUCTION: The pandemic caused by the coronavirus disease 2019 (COVID-19) infection has exposed vulnerable populations to an unprecedented global health crisis. Research reported that Chinese traditional medicine injections were used in patients with COVID-19 infection and showed significant effects, and there have been no systematic review and meta-analyses to investigate the effects and safety of Chinese traditional medicine injections. MATERIALS AND METHODS: This systematic review and meta-analysis protocol is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. The literature search will involve Cochran library, Web of science, PubMed, MEDLINE, Embase, China Biology Medicine Database, China National Knowledge Infrastructure Database, VIP, Wang Fang database, and China Clinical Trial Registration Center for articles and research published form December 2019. This search will include randomized controlled trials and nonrandomized studies. The Cochrane Collaboration's tool for randomized controlled trial studies and the Quality Assessment Tool for Quantitative Studies for nonrandomized studies will be used to assess the risk of bias among the studies included in the systematic review. Review Manager 5.3 software will be used for the meta-analysis, and odds ratio are calculated as the primary outcomes. Subgroup analyses will then be performed based on the characteristics of the interventions and populations included in the studies examined. ETHICS AND DISSEMINATION: This systematic review protocol is designed to provide evidence regarding the effects and safety of Chinese traditional medicine injections on patients with COVID-19, such evidence may be useful and important for clinical treatment decisions. The results should be disseminated through publication in a peer-reviewed journal. Since the data and results used in the systematic review will be extracted exclusively from published studies, approval from an ethics committee will not be required.

The effectiveness and safety of traditional Chinese medicine for the treatment of children with COVID-19.

INTRODUCTION: With the widespread spread of novel coronavirus pneumonia, more and more countries have been affected. Some research reports have shown that traditional Chinese medicine has a significant effect on COVID-19 infection, and the treatment of traditional Chinese medicine is used in some special people, such as children. At present, there is a lack of high-quality systematic reviews on the safety and efficacy of using Chinese medicine to treat children with novel coronavirus pneumonia. MATERIALS AND METHODS: We will search Cochran library, MEDLINE, EMBASE, China National Knowledge Infrastructure Database (CNKI), China Biomedical Database (CBM), VIP Database (VIP), and Wanfang database for research. This study includes randomized controlled trials (RCTs) and non-RCTs, and uses the Cochrane systematic review to review the safety and efficacy of traditional Chinese medicine in preventing and treating children with novel coronavirus pneumonia. RCT research tools and quantitative research quality assessment tools for non-randomized studies will be used to assess the risk of bias in studies included in the systematic review. We will use Revman 5.3 software for meta-analysis, the main result is odds ratio, and then a subgroup analysis will be performed based on the age, intervention degree, and disease severity of the patients reviewed. ETHICS AND DISSEMINATION: This systematic review protocol is designed to provide evidence regarding the effectiveness and safety of traditional Chinese medicine for the treatment of children with COVID-19, such evidence may be useful and important for clinical treatment decisions. The results should be disseminated through publication in a peer-reviewed journal. Since the data and results used in the systematic review will be extracted exclusively from published studies, approval from an ethics committee will not be required. REGISTRATION INFORMATION: PROSPERO CRD42020179150.