Integrated time-series transcriptomic and metabolomic analyses reveal different inflammatory and adaptive immune responses contributing to host resistance to PRRSV.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.

Factors Associated With Protective Mask-Wearing Behavior to Avoid COVID-19 Infection in China: Internet-Based Cross-sectional Study.

BACKGROUND: The novel coronavirus disease COVID-19 is likely to spread from person to person in close-contact settings. The Chinese Center for Disease Control and Prevention released a handbook on COVID-19, which introduced health information to the public, specifically related to wearing masks correctly and adopting preventive measures to avoid COVID-19 infection. OBJECTIVE: The aim of this study was to assess the level of mask knowledge, behavior related to mask usage, and major information channels used for obtaining mask- and COVID-19-related information in China. METHODS: An internet-based survey was conducted primarily using DingXiang Doctor WeChat public accounts. The data about mask knowledge and behavior were collected and analyzed. In addition to descriptive statistics, logistic regression was used to analyze significant risk factors contributing to protective mask behavior. RESULTS: Data were collected from a total of 10,304 respondents to the survey. More than half of the respondents were under 30 years old and nearly three-quarters were women. Over 80% of participants had a bachelor's degree or higher, and the largest proportion of respondents (n=4204, 40.80%) were employed as business/service workers. Over half of the study participants were married (n=5302, 51.46%). The findings revealed that 67.49% (6954/10,304) of the participants practiced protective mask behavior; 97.93% (10,091/10,304) believed that wearing masks is an effective protective measure against COVID-19; 96.85% (9979/10,304) chose a mask that has two or more layers of washable, breathable fabric; and 70.57% (7272/10,304) wore the masks correctly. Gender, age, occupation, and education level had significant effects on behavior, whereas marital status and the infection status of family members were not significantly related to mask-wearing behavior. In addition, WeChat public accounts (9227/10,304, 89.55%) were the most prominent source of obtaining health information for Chinese netizens after the outbreak of COVID-19. CONCLUSIONS: This study elucidated that Chinese netizens' protective mask behavior is far lower than their mask-related knowledge. Improved information channels and adequate information on wearing masks are necessary to improve the public's protective mask behavior, particularly among men, the elderly, and people with less education.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

Would Older Adults Perform Preventive Practices in the Post-COVID-19 Era? A Community-Based Cross-Sectional Survey in China.

During the post-COVID-19 era, preventive practices, such as washing hands and wearing a mask, remain key measures for controlling the spread of infection for older adults. This study investigated the status of preventive practices among older adults and identified the related influencing factors. Participants who were ≥60 years old were recruited nationwide. Data were collected through self-designed questionnaires, including demographic variables, knowledge, perceived vulnerability, response efficacy, anxiety and preventive practices. Descriptive statistics and chi-square tests were performed. Hierarchical logistic regression was conducted to determine the predictors. A total of 2996 participants completed this study. Of them, 2358 (78.7%) participants reported washing hands regularly in the last two weeks, and 1699 (56.7%) always wore masks outside this year. Knowledge (hand washing: OR = 1.09, p < 0.01; mask wearing: OR = 1.17, p < 0.01) and response efficacy (hand washing: OR = 1.61, p < 0.01; mask wearing: OR = 1.70, p < 0.01) were positively associated with preventive practices, whereas perceived vulnerability had a negative effect (hand washing: OR = 0.54, p < 0.01; mask wearing: OR = 0.72, p < 0.01). Knowledge, response efficacy and perceived vulnerability were found to be significant predictors of the preventive practice among older adults in the post-COVID-19 era. This study provides new insights into preventive suggestions after the peak of the pandemic and also has significant implications in improving the life quality of older adults.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Clinical characteristics and outcomes in coronavirus disease 2019 (COVID-19) patients with and without hypertension: a retrospective study.

The novel coronavirus disease (COVID-19) has spread all over the world in a short time. Information about the differences between COVID-19 patients with and without hypertension is limited. To explore the characteristics and outcomes differences between COVID-19 patients with and without hypertension, the medical records and cardiac biomarkers of 414 patients were analyzed. A total of 149 patients had a history of hypertension, while 265 patients did not have hypertension, and the groups were compared based on their clinical characteristics and laboratory findings as well as the hazard risk for composite outcomes, including intensive care unit (ICU) admission, mechanical ventilation, or death. The results are as follows. On admission, 22.1% of patients in hypertension group had elevated high sensitivity troponin I (hs-TNI > 26 pg/mL), which was higher than the proportion in the nonhypertension group (6.4%). Median NT-proBNP levels in patients with hypertension (141.9 pg/mL) were higher than those in patients without hypertension (77.3 pg/mL). Patients in the hypertension group had a higher risk for in-hospital death [HR: 2.57, 95% CI (1.46~4.51)]. However, the impact of hypertension on the prognosis was not significant after adjusting for age and sex. Multivariate Cox hazard regression confirmed that NT-proBNP levels in the highest tertile (upper 75 % of patients with hypertension) was an independent risk factor for in-hospital death in all COVID-19 patients. Taken together, hypertension per se had a modest impact on the prognosis in COVID-19 patients. In COVID-19 patients with and without hypertension, NT-proBNP may be a better predictor of prognosis than hs-TNI.

Concerns About Information Regarding COVID-19 on the Internet: Cross-Sectional Study.

BACKGROUND: Since the outbreak of COVID-19, the Chinese government and the Chinese Center for Disease Control and Prevention have released COVID-19-related information to the public through various channels to raise their concern level of the pandemic, increase their knowledge of disease prevention, and ensure the uptake of proper preventive practices. OBJECTIVE: Our objectives were to determine Chinese netizens' concerns related to COVID-19 and the relationship between their concerns and information on the internet. We also aimed to elucidate the association between individuals' levels of concern, knowledge, and behaviors related to COVID-19. METHODS: The questionnaire, which consisted of 15 closed-ended questions, was designed to investigate Chinese netizens' knowledge about COVID-19. The self-selection online survey method of nonprobability sampling was used to recruit participants through Dingxiangyisheng WeChat (a public, medical, and health service platform in China) accounts. Standard descriptive statistics and multivariate logistic regression analyses were conducted to analyze the data. RESULTS: In total, 10,304 respondents were surveyed on the internet (response rate=1.75%; 10,304/590,000). Nearly all (n=9803, 95.30%) participants were concerned about "confirmed cases" of COVID-19, and 87.70% (n=9036) received information about the outbreak through social media websites. There were significant differences in participants' concerns by sex (P=.02), age (P<.001), educational attainment (P=.001), and occupation (P<.001). All knowledge questions and preventive practices were associated with concerns about COVID-19. The results of the multivariate logistic regression indicated that participants' sex, educational attainment, occupation and employment status, knowledge acquisition, and concern level were significantly associated with the practice of proper preventive behaviors. CONCLUSIONS: This study elucidated Chinese netizens' concerns, information sources, and preventive behaviors related to the COVID-19 pandemic. Sex, educational attainment, occupation and employment status, knowledge acquisition, and level of concern were key factors associated with proper preventive behaviors. This offers a theoretical basis for the government to provide targeted disease prevention and control information to the public.

Measures Undertaken in China to Avoid COVID-19 Infection: Internet-Based, Cross-Sectional Survey Study.

BACKGROUND: In early 2020, over 80,000 cases of coronavirus disease (COVID-19) were confirmed in China. Public prevention and control measures, along with efforts from all sectors of society, were undertaken to control and eliminate disease transmission. OBJECTIVE: This paper describes Chinese citizens' response to the epidemic, the preventive measures they implemented to avoid being infected, and the public strategies that were carried out by the government, health workers, etc. We also discuss the efficacy of these measures in controlling the epidemic in China. METHODS: Information on the responses and behaviors of Chinese citizens were collected through a cross-sectional, internet-based survey using Dingxiang Doctor's public account on WeChat. Information on public strategies implemented by all sectors of society to control the epidemic and data on new COVID-19 cases were collected from the internet, mainly from government websites. Standard descriptive statistics and multivariate logistic regression analyses were conducted to analyze the data. RESULTS: A total of 10,304 participants responded to the survey, with 10,198 valid responses; 74.1% (n=7557) were female and 25.9% (n=2641) were male. Overall, 98.2% (n=10,013) of participants paid high or very high attention to the epidemic, with WeChat being their main information source (n=9400, 92.2%). Over half the participants (n=5878, 57.7%) were confident that the epidemic could be curbed in China; 92.4% (n=9427) opened windows for ventilation more frequently than usual; 97.9% (n=9986) used masks in public; 95.7% (n=9759) avoided large crowds and stayed at home as much as possible; and 97.9% (n=9988) washed their hands more often than usual. Women were more likely to practice these behaviors than men (P<.001). With a series of strict public control measures, like nationwide health education campaigns, holiday extensions, the Examine and Approve Policy on the resumption of work, close management of working and living quarters, a health QR (Quick Response) code system, community screening, and social distancing policies, the number of new cases have decreased dramatically since February 12, 2020. CONCLUSIONS: The methods employed by Chinese citizens and authorities have effectively curtailed the spread of COVID-19, demonstrating that this pandemic can be brought under control as long as the right measures are taken.