Oral administration of Lactic acid bacteria inhibits PEDV infection in young piglets.

Since the emergence of the highly pathogenic porcine epidemic diarrhea virus (PEDV) strain in 2010, the prevention of porcine epidemic diarrhea (PED) in pig farms remains problematic. To find the reasons behind the high mortality in young piglets, the relative mRNA expression of inflammation-related factors in infected pigs of different ages as well as uninfected pigs were detected by RT-qPCR. The results showed that the mRNA expression of these factors including IL-6 and TNF-α was more increased in infected younger piglets than infected older pigs. To clarify the relationship between these inflammation related factors, the pairwise linear correlation between the relative expression of these factors were analyzed and showed as network mapping with different correlation coefficients. A strong positive correlation was observed between the expression of various factors in 1-week-old piglets. Combined with the difference in mortality of PEDV infection in pigs of different ages, we hypothesized that lactic acid bacteria (LAB) could inhibit PEDV infection in newborn piglets, and an in vivo experiment was carried out. The results of survival rate and wet/dry ratio showed that LAB alleviated PEDV indued mortality and diarrhea. The detection of viral copies and tissue section staining showed less observed viruses in LAB treated pig. RT-qPCR results of gene expression in intestines showed that LAB modulated the gene expression of various host barrier genes, indicating that LAB is potential to inhibit PEDV infection by regulating the host intestinal barrier. However, to use LAB as therapy, how to improve the efficiency on inhibiting PEDV infection needs further studies.

Transmissible Gastroenteritis Virus Infection Promotes the Self-Renewal of Porcine Intestinal Stem Cells via Wnt/ß-Catenin Pathway.

Intestinal stem cells (ISCs) play an important role in tissue repair after injury. A recent report delineates the effect of transmissible gastroenteritis virus (TGEV) infection on the small intestine of recovered pigs. However, the mechanism behind the epithelium regeneration upon TGEV infection remains unclear. To address this, we established a TGEV infection model based on the porcine intestinal organoid monolayer. The results illustrated that the porcine intestinal organoid monolayer was susceptible to TGEV. In addition, the TGEV infection initiated the interferon and inflammatory responses following the loss of absorptive enterocytes and goblet cells. However, TGEV infection did not disturb epithelial integrity but induced the proliferation of ISCs. Furthermore, TGEV infection activated the Wnt/ß-catenin pathway by upregulating the accumulation and nuclear translocation of ß-catenin, as well as promoting the expression of Wnt target genes, such as C-myc, Cyclin D1, Mmp7, Lgr5, and Sox9, which were associated with the self-renewal of ISCs. Collectively, these data demonstrated that the TGEV infection activated the Wnt/ß-catenin pathway to promote the self-renewal of ISCs and resulted in intestinal epithelium regeneration. IMPORTANCE The intestinal epithelium is a physical barrier to enteric viruses and commensal bacteria. It plays an essential role in maintaining the balance between the host and intestinal microenvironment. In addition, intestinal stem cells (ISCs) are responsible for tissue repair after injury. Therefore, prompt self-renewal of intestinal epithelium will facilitate the rebuilding of the physical barrier and maintain gut health. In the manuscript, we found that the transmissible gastroenteritis virus (TGEV) infection did not disturb epithelial integrity but induced the proliferation of ISCs and facilitated epithelium regeneration. Detailed mechanism investigations revealed that the TGEV infection activated the Wnt/ß-catenin pathway to promote the self-renewal of ISCs and resulted in intestinal epithelium regeneration. These findings will contribute to understanding the mechanism of intestinal epithelial regeneration and reparation upon viral infection.

Elevated D-dimer and Adverse In-hospital Outcomes in COVID-19 Patients and Synergism with Hyperglycemia.

Aim: One of the most common laboratory findings in COVID-19 patients has been observed to be hypercoagulability with elevated D-dimer levels. An activation of thrombosis may be generated by hyperglycemia. We aimed to explore the association between D-dimer and in-hospital outcomes, and evaluate the synergistic effect between elevated D-dimer and hyperglycemia on COVID-19 prognosis. Methods: A retrospective cohort study was undertaken with 2467 COVID-19 inpatients. D-dimer and fasting blood glucose (FBG) on admission and adverse in-hospital outcomes (events of death and aggravated severity) were collected. Cox proportional risk model was performed to assess the association of D-dimer and adverse in-hospital outcomes, and the combined effects of D-dimer and FBG. Results: Among these COVID-19 patients, 1100 (44.6%) patients had high D-dimer (≥0.50 mg/L). Patients with high D-dimer were older, with higher FBG (≥7.00 mmol/L), and had significantly higher adjusted risk of adverse in-hospital outcomes when comparing with those who with D-dimer<0.50 mg/L (hazard ratio, 2.73; 95% confidence interval, 1.46-5.11). Moreover, patients with high FBG and D-dimer levels had an increasing risk (hazard ratio, 5.72; 95% confidence interval: 2.65-12.34) than those with normal FBG and D-dimer. Conclusion: Risk of adverse in-hospital outcomes is higher among patients with high D-dimer levels. Additionally, this study found for the first time that elevated D-dimer and hyperglycemia had a synergistic effect on COVID-19 prognosis, and this risk was independent of diabetes history.

A database of anti-coronavirus peptides.

Since 2019, the novel coronavirus (SARS-COV-2) disease (COVID-19) has caused a worldwide epidemic. Anti-coronavirus peptides (ACovPs), a type of antimicrobial peptides (AMPs), have demonstrated excellent inhibitory effects on coronaviruses. However, state-of-the-art AMP databases contain only a small number of ACovPs. Additionally, the fields of these databases are not uniform, and the units or evaluation standards of the same field are inconsistent. Most of these databases have not included the target domains of ACovPs and description of in vitro and in vivo assays to measure the inhibitory effects of ACovPs. Here, we present a database focused on ACovPs (ACovPepDB), which contains comprehensive and precise ACovPs information of 518 entries with 214 unique ACovPs manually collected from public databases and published peer-reviewed articles. We believe that ACovPepDB is of great significance for facilitating the development of new peptides and improving treatment for coronavirus infection. The database will become a portal for ACovPs and guide and help researchers perform further studies. The ACovPepDB is available at http://i.uestc.edu.cn/ACovPepDB/ .

Patients with COVID-19 and HBV Coinfection are at Risk of Poor Prognosis.

INTRODUCTION: This study aimed to determine whether there is a difference in the risk of death/critical illness between different stages of hepatitis B virus (HBV) (resolved hepatitis B, HBeAg (-) chronic hepatitis B [CHB]/infection, HBeAg (+) CHB/infection, and HBV reactivation) coinfected with coronavirus disease 2019 (COVID-19); and if there is a difference, whether it is due to abnormal liver function and to what extent. METHODS: This cohort study included all COVID-19 inpatients of a single-center tertiary care academic hospital in Wuhan, Hubei, China, between February 4, 2020, and follow-up to April 14, 2020. A total of 2899 patients with COVID-19 were included as participants in this study, and they were divided into five groups based on hepatitis B infection status. Follow-up was conducted for mortality and ICU admission during hospitalization. RESULTS: The median follow-up time was 39 days (IQR, 30-50), with 66 deaths and 126 ICU admissions. After adjustment, compared with patients without CHB, the hazard ratio (HR) for ICU admission was 1.86 (95% CI: 1.05-3.31) for patients with HBeAg (+) CHB/infection. The HR for death was 3.19 (95% CI: 1.62-6.25) for patients with HBeAg (+) CHB/infection. The results for the mediating effect indicated that the total effect of HBeAg (+) CHB/infection on death/ICU stay was partially mediated by abnormal liver function, which accounted for 79.60% and 73.53%, respectively. CONCLUSION: Patients with COVID-19 coinfected with HBV at the HBeAg (+) CHB/infection stage have an increased risk of poor prognosis, and abnormal liver function partially mediates this increased risk of poor prognosis caused by the coinfection.

The association between BMI and metabolically unhealthy status with COVID-19 mortality: Based on 3019 inpatients from Wuhan, China.

BACKGROUND AND AIMS: Patients with multiple metabolic diseases are at high risk for the occurrence and death of COVID-19. Little is known about patients with underweight and metabolically healthy obesity. The aim of this study is to evaluate the impact of BMI and COVID-19 mortality in hospitalized patients, and also explore the association in different metabolically healthy (MHS) and unhealthy status (MUS). METHODS AND RESULTS: A retrospective cohort study based on 3019 inpatients from Wuhan was conducted. Included patients were classified into four groups according the BMI level (underweight, normal weight, overweight and obesity), and patients with at least one of the metabolic abnormalities (diabetes, hypertension, dyslipidemia) was defined as MUS. Multiple Cox model was used to calculate the hazard ratio (HR). Compared to patients with normal weight, the HRs of overweight and obesity for COVID-19 mortality were 1.91 (95%CI:1.02-3.58) and 2.54 (95%CI:1.22-5.25) respectively in total patients, and 2.58 (95%CI:1.16-5.75) and 3.89 (95%CI:1.62-9.32) respectively in the elderly. The HR of underweight for COVID-19 mortality was 4.58 (95%CI:1.56-13.48) in the elderly. For different metabolic statuses, both underweight, overweight and obesity had obviously negative association with COVID-19 mortality in total and elderly patients with MUS. However, no significance was found in non-elderly and patients with MHS. CONCLUSION: Not only overweight or obesity, but also underweight can be associated with COVID-9 mortality, especially in the elderly and in patients with MUS. More large-scale studies are needed for patients with underweight and metabolically healthy overweight or obesity.

Smart city projects against COVID-19: Quantitative evidence from China.

The outbreak of COVID-19 pandemic worldwide has brought huge challenges to urban governance. Whether the smart city projects play a significant role in the COVID-19 prevention and control process is a question worthy of attention. Based on the data of COVID-19 confirmed cases and the smart cities projects investment in China cities, our empirical results show that smart city projects have significantly reduced the number of COVID-19 confirmed cases. Specifically, for every 1 million yuan increase in smart city investment per 10,000 people, the number of COVID-19 confirmed cases per 10,000 people would decrease by 0.342. The heterogeneity analysis results show that the effect of the smart city projects on COVID-19 in the spread phase inside a city is stronger than that in the input phase. In addition, the effect differs for cities with different population sizes. This study provides quantitative evidence of the impact of smart city projects on COVID-19 prevention and control.

Single-cell transcriptomic atlas of primate cardiopulmonary aging.

Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.