Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase.

COVID-19 has become a global public health crisis since its outbreak in China in December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 are involved in the viral replication, and might be prospective targets for anti-coronavirus drug development. Here, we investigated the antiviral activity of oridonin, a natural small-molecule compound, against SARS-CoV-2 infection in vitro. The time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry stage. Mechanistically, the inhibition of viral replication by oridonin depends on the oxidation activity of α, ß-unsaturated carbonyl. Further experiments showed that oridonin not only effectively inhibited SARS-CoV-2 Mpro activity, but also had some inhibitory effects on PLpro-mediated deubiquitinating and viral polymerase-catalyzed RNA elongation activities at high concentrations. In particular, oridonin could inhibit the bat SARS-like CoV and the newly emerged SARS-CoV-2 omicron variants (BA.1 and BA.2), which highlights its potential as a pan-coronavirus antiviral agent. Overall, our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.

Serum 25-Hydroxy Vitamin D Levels in Children with Acute Respiratory Infections Caused by Respiratory Virus or Atypical Pathogen Infection.

We aimed to clarify the involvement of vitamin D status in virus or atypical pathogens infection in children with acute respiratory infections (ARIs). In this retrospective study, 295 patients with ARIs were attacked by a respiratory virus or a single atypical pathogen; 17 patients with ARIs induced by two pathogens, and 636 healthy children were included. Serum 25(OH)D levels of all children were measured. Oropharyngeal samples of the patients for viruses or atypical pathogens were studied by polymerase chain reaction (PCR) or reverse transcription-polymerase chain reaction (RT-PCR). In our studies, 58.98% of the 295 single-infected subjects and 76.47% of the 17 co-infected subjects had 25(OH)D levels below the recommended 50.0 nmol/L; the mean 25(OH)D levels were 48.48 ± 19.91 nmol/L and 44.12 ± 12.78 nmol/L. Low serum 25(OH)D levels were remarkable in patients with one of seven viruses or atypical pathogens infected. These results were significantly different from those in the healthy group. There were no significant differences in 25(OH)D levels between single infection and co-infection groups. There were no differences in severity among means of 25(OH)D levels. Female or >6-year-old children patients with low serum 25(OH)D levels were more vulnerable to pathogenic respiratory pathogens. However, serum 25(OH)D levels may be related to the recovery of ARIs. These findings provide additional evidence for the development of strategies to prevent ARIs in children.

Comparison of anthropometric parameters and laboratory test results before and after the COVID-19 outbreak among Chinese children aged 3-18 years.

Objective: To compare the physiological health of Chinese children around the COVID-19 lockdown. Methods: We extracted data on children's anthropometric and laboratory parameters from May to November in both 2019 and 2020 from the Health Checkup Center, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China. Overall, 2162 children aged 3~18 years without comorbidities in 2019 and 2646 in 2020 were assessed. Mann Whitney U tests were used to compare differences between the above health indicators before and after COVID-19 outbreak. Quantile regression analyses adjusted for age, sex and body mass index (BMI) were also used in analysis. Chi-square tests and Fisher's exact tests were used for comparing differences of categorical variables. Results: Compared with children examined in 2019 before the outbreak, children in 2020 had a higher median z score of BMI for age (-0.16 vs. -0.31), total cholesterol (TC, 4.34 vs. 4.16 mmol/L), low density lipoprotein cholesterol (LDL-C, 2.48 vs. 2.15 mmol/L), high density lipoprotein cholesterol (HDL-C, 1.45 vs. 1.43 mmol/L) and serum uric acid (290 vs. 282 µmol/L), and a lower hemoglobin (Hb, 134 vs. 133 g/L), triglycerides (TG, 0.70 vs. 0.78 mmol/L) and 25(OH)D (45.8 vs. 52.2 nmol/L), all P < 0.05. No differences were identified for waist height ratio, blood pressure and fasting glucose (both P > 0.05). However, in regression models after adjusting, BMI, TC, LDL-C, blood glucose and sUA were positively correlated with year; while Hb, TG and 25(OH)D were negatively correlated with year (all P < 0.05). Accordingly, children in 2020 had a higher prevalence of overweight/obesity (20.6 vs. 16.7%, P < 0.001), hypercholesterol (16.2%vs. 10.2%, P < 0.001), high LDL-C (10 vs. 2.9%, P < 0.001), hyperuricemia (18.9 vs.15.1%, P = 0.002), vitamin D deficiency (22.6 vs. 8.1%, P < 0.001) and a lower prevalence of high TG (4.3 vs. 2.8%, P = 0.018) compared with children in 2019. Conclusion: In this real-world study, we found that long-term lockdown due to COVID-19 outbreak might cause adverse impact on children's metabolic health, which might increase their future risk of cardiovascular diseases. Thus, parents, health professionals, educationists, and caregivers should pay more attention to children's dietary pattern and lifestyle, especially in this new normal against COVID-19.

Intranasal delivery of replicating mRNA encoding hACE2-targeting antibody against SARS-CoV-2 Omicron infection in the hamster.

The Omicron variant is sweeping the world, which displays striking immune escape potential through mutations at key antigenic sites on the spike protein, making broad-spectrum SARS-CoV-2 prevention or therapeutical strategies urgently needed. Previously, we have reported a hACE2-targeting neutralizing antibody 3E8, which could efficiently block both prototype SARS-CoV-2 and Delta variant infections in prophylactic mouse models, having the potential of broad-spectrum to prevent SARS-CoV-2. However, preparation of monoclonal neutralizing antibodies is severely limited by the time-consuming process and the relative high cost. Here, we utilized a modified VEEV replicon with two subgenomic (sg) promoters engineered to express the light and heavy chains of the 3E8 mAb. The feasibility and protective efficacy of replicating mRNA encoding 3E8 against Omicron infection in the hamster were demonstrated through the lung targeting delivery with the help of VEEV-VRP. Overall, we developed a safe and cost-effective platform of broad-spectrum to prevent SARS-CoV-2 infection.

Human adenovirus (HAdV) infection in children with acute respiratory tract infections in Guangzhou, China, 2010-2021: a molecular epidemiology study.

BACKGROUND: Human adenovirus (HAdV) infection can cause a variety of diseases. It is a major pathogen of pediatric acute respiratory tract infections (ARIs) and can be life-threatening in younger children. We described the epidemiology and subtypes shifting of HAdV among children with ARI in Guangzhou, China. METHODS: We conducted a retrospective study of 161,079 children diagnosed with acute respiratory illness at the Guangzhou Women and Children's Medical Center between 2010 and 2021. HAdV specimens were detected by real-time PCR and the hexon gene was used for phylogenetic analysis. RESULTS: Before the COVID-19 outbreak in Guangzhou, the annual frequency of adenovirus infection detected during this period ranged from 3.92% to 13.58%, with an epidemic peak every four to five years. HAdV demonstrated a clear seasonal distribution, with the lowest positivity in March and peaking during summer (July or August) every year. A significant increase in HAdV cases was recorded for 2018 and 2019, which coincided with a shift in the dominant HAdV subtype from HAdV-3 to HAdV-7. The latter was associated with a more severe disease compared to HAdV-3. The average mortality proportion for children infected with HAdV from 2016 to 2019 was 0.38% but increased to 20% in severe cases. After COVID-19 emerged, HAdV cases dropped to 2.68%, suggesting that non-pharmaceutical interventions probably reduced the transmission of HAdV in the community. CONCLUSION: Our study provides the foundation for the understanding of the epidemiology of HAdV and its associated risks in children in Southern China.

The influence of perceived risks on millennials' intention to use m-payment for mobile shopping in Bangkok

Purpose>Booming mobile shopping has resulted in an increase use of m-payment. Although m-payment is still in its infancy in Thailand, it has started to affect the daily lives of Thai people. This study aims to understand the role of perceive risks in influencing millennials' intention to use m-payment for mobile shopping.Design/methodology/approach>The sample covers 250 millennials in Bangkok who were surveyed between February to May 2019. Purposive sampling and convenient sampling were applied to collect data. Partial least squares structural equation modelling (PLS-SEM) was applied for statistical analysis. Further, mediation effect of attitude was studied.Findings>The results showed that only perceived time risk significantly but negatively affect millennials' attitude towards using m-payment. Moreover, mediation test confirms that the relationship between perceived time risk and intention to use m-payment is mediated by attitude.Research limitations/implications>First, limited number of respondents cannot be a representative of millennials as a whole. Second, the study is limited to a general study, in which the results of m-payment might not be effectual to explain other scenarios (e.g. offline setting) and the market situation in another cultural context.Practical implications>It is important that business practitioners should formulate less complicated system under the most decent transaction time to elicit positive attitude towards m-payment. Also, message should emphasize on the time being saved and simplicity of the m-payment.Originality/value>Since the study of how perceived risks influence millennials intention to m-payment remains insufficient in Southeast Asian context especially in Thailand, this paper contributes to the updating of empirical findings to the existing literatures.

Problematic Internet Use Was Associated With Psychological Problems Among University Students During COVID-19 Outbreak in China.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed globally, school closures and home quarantine may cause an increase in problematic Internet use among students in universities. Such a traumatic stress event may also contribute to the development of posttraumatic stress disorder (PTSD), depressive, and anxiety symptoms. This study aimed to evaluate the prevalence of PTSD, depressive, and anxiety symptoms as well as the predictive role of problematic Internet use in the above-mentioned psychological problems in university students. Methods: A cross-sectional study was conducted through an online survey of 8,879 students in China between April 20 and April 26, 2020. The presence of PTSD, depressive, and anxiety symptoms and problematic Internet use were evaluated using PTSD Checklist for DSM-5, the Center for Epidemiologic Studies Depression 9-item scale, the generalized anxiety disorder 7-item scale, and the Young diagnostic questionnaire, respectively. Sociodemographic information and the knowledge, attitude, and practice (KAP) toward COVID-19 data were also collected. Results: A total of 4,834 (54.4%) participants were female, and 7,564 (85.2%) were undergraduate students. A total of 615 students (6.9%) reported PTSD symptoms; 5.2% (465) and 10.1% (896) reported moderate to severe depressive and anxiety symptoms, respectively. The problematic Internet use was significantly associated with higher risk of PTSD, depressive, and anxiety symptoms (odds ratio 2.662 [95% CI, 2.239-3.165], odds ratio 4.582 [95% CI, 3.753-5.611], odds ratio 3.251 [95% CI, 2.814-3.757], respectively; all P < 0.001). Lower attitude and practice scores also contributed to the risk of depressive, anxiety, and PTSD symptoms (P < 0.05). Conclusions: Psychological problems should be paid more attention, and problematic Internet use may be a predictor when screening high-risk students for psychological problems. Our results will aid in timely psychological screening, which is meaningful in the prevention and intervention of psychological problems.

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study.

OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge. METHODS: This 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index. RESULTS: Fasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 µg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index. CONCLUSION: Our study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.

[Discussion on the effect pathways of preventing and treating coronavirus disease 2019 by acupuncture and moxibustion from the regulation of immune inflammatory response].

The effect of acupuncture-moxibustion on respiratory system and systemic immune inflammatory response were reviewed to explore the possible role of neuroimmunomodulation in the control of inflammatory response and the effect mechanism of cholinergic anti-inflammatory pathway on coronavirus disease 2019 (COVID-19). Acupuncture-moxibustion could produce the local and systemic anti-inflammatory effect on COVID-19 through the activation of cholinergic anti-inflammatory pathway. Compared with humoral anti-inflammatory pathway, the neuronal anti-inflammatory pathway has earlier initiation, rapider action, and more localization, which play a more important role in the initial stage of inflammatory response. This may be an important basis for acupuncture-moxibustion intervention in the early stage of COVID-19. In addition to cholinergic anti-inflammatory pathway, acupuncture-moxibustion may also play an anti-inflammatory role in activating sympathetic nerve, hypothalamic-pituitary-adrenal axis and other neural anti-inflammatory pathways. How acupuncture-moxibustion play its role in stimulating the vagus nerve and sympathetic nerve in different periods of inflammatory response, and whether the effect is based on the selection of acupoints and the methods of stimulation, will be the research direction of the transformation from basic research to clinical research for acupuncture-moxibustion.

J-shaped association between fasting blood glucose levels and COVID-19 severity in patients without diabetes.

AIMS: Coronavirus disease 2019 (COVID-19) has become a recognized worldwide pandemic. Researchers now know that mortality from COVID-19 can be reduced through early prevention measures. This retrospective, multi-centered study of 293 COVID-19 patients without diabetes explores the association between fasting blood glucose (FBG) levels and the risk of COVID-19 disease progression, with the goal of providing clinical evidence for glycemic targets in patients. METHODS: The multivariate stepwise binary logistic regression analysis was used to test the dose-response effects of FBG levels on the risk of severe and critical condition in COVID-19 patients. RESULTS: FBG levels were plotted in quintiles with set at <4.74, 4.74-5.21, 5.21-5.78, 5.78-7.05, and ≧7.05 mmol/L. The constituent ratio of severe or critical cases in each FBG quintile was 20.7%, 1.7%, 13.8%, 27.1%, and 67.2%, respectively (P < 0.0001). When the second quintile was used as the reference, the adjusted odds ratios (AORs) (95%CI) for the risk of severe/critical condition in COVID-19 was 25.33 (2.77, 231.64), 1.00 (Reference), 3.13 (0.33, 29.67), 10.59 (1.23, 91.24), 38.93 (4.36, 347.48) per FBG quintile respectively (P < 0.001). CONCLUSIONS: We provide evidence of J-shaped associations between FBG and risk of severe and critical condition in non-diabetes patients with COVID-19, with nadir at 4.74-5.78 mmol/L.

Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.

We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal-oral transmission.