Recombinant human adenovirus type 5 based vaccine candidates against GIIa- and GIIb-genotype porcine epidemic diarrhea virus induce robust humoral and cellular response in mice.

Porcine epidemic diarrhea virus (PEDV) is a porcine enteropathogenic coronavirus causing severe watery diarrhea, vomiting, dehydration, and death in piglets. However, most commercial vaccines are developed based on the GI genotype strains, and have poor immune protection against the currently dominant GII genotype strains. Therefore, four novel replication-deficient human adenovirus 5-vectored vaccines expressing codon-optimized forms of the GIIa and GIIb strain spike and S1 glycoproteins were constructed, and their immunogenicity was evaluated in mice by intramuscular (IM) injection. All the recombinant adenoviruses generated robust immune responses, and the immunogenicity of recombinant adenoviruses against the GIIa strain was stronger than that of recombinant adenoviruses against the GIIb strain. Moreover, Ad-XT-tPA-Sopt-vaccinated mice elicited optimal immune effects. In contrast, mice immunized with Ad-XT-tPA-Sopt by oral gavage did not induce strong immune responses. Overall, IM administration of Ad-XT-tPA-Sopt is a promising strategy against PEDV, and this study provides useful information for developing viral vector-based vaccines.

The Influence of Media Information Sources on Preventive Behaviors in China: After the Outbreak of COVID-19 Pandemic.

Background: As announced by the World Health Organization (WHO), since March 2020, the COVID-19 pandemic has become a global pandemic. In order to prevent the spread of COVID-19, Chinese government carried out very strict prevention and control policy. Objective: The study aimed to explore the effect of news reports on COVID-19 vaccine from traditional media and social media on COVID-19 preventive behaviors. Methods: Adults aged between 18 and 58 years old completed an online survey reporting how they gathered media information sources regarding the COVID-19 vaccine, as well as any details relating to risk perception, vaccine efficacy, and preventive behaviors in COVID-19 pandemic. Results: Our results showed that traditional and social media information sources both significantly and positively influenced people's COVID-19 preventive behaviors, with the former showing a stronger effect. COVID-19 contact risk perception and vaccine efficacy awareness of media audiences partly mediate this relationship. Audiences who reported more exposing news reports on COVID-19 vaccine from the media show stronger risk perception and vaccine efficacy awareness. This increases their COVID-19 preventive behaviors. Conclusions: This study found that media information sources have an important impact on people's COVID-19 preventive behaviors. People believe more in the news information of the mainstream media about the COVID-19 pandemic. Moreover, much of the news information of social media is also from the important mainstream media. Media organizations should shoulder greater social responsibility, embed the health-related benefits of COVID-19 vaccination into the values and cultural order of the whole society, find and shape a common space of meaning, and produce forms of internal coupling and value identification.

Updating and Evaluating Anthropogenic Emissions for NOAA's Global Ensemble Forecast Systems for Aerosols (GEFS-Aerosols): Application of an SO2 Bias-Scaling Method

We updated the anthropogenic emissions inventory in NOAA's operational Global Ensemble Forecast for Aerosols (GEFS-Aerosols) to improve the model's prediction of aerosol optical depth (AOD). We used a methodology to quickly update the pivotal global anthropogenic sulfur dioxide (SO2) emissions using a speciated AOD bias-scaling method. The AOD bias-scaling method is based on the latest model predictions compared to NASA's Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA2). The model bias was subsequently applied to the CEDS 2019 SO2 emissions for adjustment. The monthly mean GEFS-Aerosols AOD predictions were evaluated against a suite of satellite observations (e.g., MISR, VIIRS, and MODIS), ground-based AERONET observations, and the International Cooperative for Aerosol Prediction (ICAP) ensemble results. The results show that transitioning from CEDS 2014 to CEDS 2019 emissions data led to a significant improvement in the operational GEFS-Aerosols model performance, and applying the bias-scaled SO2 emissions could further improve global AOD distributions. The biases of the simulated AODs against the observed AODs varied with observation type and seasons by a factor of 3~13 and 2~10, respectively. The global AOD distributions showed that the differences in the simulations against ICAP, MISR, VIIRS, and MODIS were the largest in March–May (MAM) and the smallest in December–February (DJF). When evaluating against the ground-truth AERONET data, the bias-scaling methods improved the global seasonal correlation (r), Index of Agreement (IOA), and mean biases, except for the MAM season, when the negative regional biases were exacerbated compared to the positive regional biases. The effect of bias-scaling had the most beneficial impact on model performance in the regions dominated by anthropogenic emissions, such as East Asia. However, it showed less improvement in other areas impacted by the greater relative transport of natural emissions sources, such as India. The accuracies of the reference observation or assimilation data for the adjusted inputs and the model physics for outputs, and the selection of regions with less seasonal emissions of natural aerosols determine the success of the bias-scaling methods. A companion study on emission scaling of anthropogenic absorbing aerosols needs further improved aerosol prediction.

Using Healthcare Complaints Analysis Tool to Evaluate Patient Complaints during the COVID-19 Pandemic at a Medical Center in Taiwan.

The purpose of this study is to evaluate patient complaints using the Healthcare Complaints Analysis Tool (HCAT) during the COVID-19 pandemic in 2021 in Taiwan. Additionally, the study examines the distribution and type of patient complaints before and during the COVID-19 pandemic to provide a better clinical procedure, hospital management and patient relationship. This study utilizes a cross-sectional design. We collected patient complaints from January 2021 to December 2021 at a medical center in Southern Taiwan. Using the Healthcare Complaints Analysis Tool (HCAT), the patient complaints are classified and coded into three major domains (clinical, management and relationship), and seven problem categories (quality, safety, environment, institutional process, respect and patient rights, listening and communication). We further compared and categorized the complaints based on whether they were COVID-19-related or not and whether it was before or during the COVID-19 pandemic to understand the differences in patient complaints. In total, we collected 584 events of patient complaints. Based on the HCAT domains, the complaints about management were the highest, at 52.9%, followed by complaints about relationship, about 37.7%. According to the types of problem, the complaints about the environment were the highest, about 32.5% (190/584), followed by communication at about 29.6% (173/584), and institutional process at about 20.4% (119/584). There were 178 COVID-19-related complaints and they were made more frequently during Q3 and Q4 (from mid-June to December) which was the pandemic period in 2021 in Taiwan. Among the COVID-19-related complaints, the most frequent were in the environment domain with 114 cases (about 65.7% of COVID-19-related complaints). The domains of patient complaints were statistically different between COVID-19-related and non-related (p < 0.001). During the COVID-19 pandemic, the proportion of COVID-19-related complaints increased 1.67 times (117/312 vs. 61/272, p < 0.001). Both prior to and during the COVID-19 pandemic, management-related complaints represented the highest domain. During the COVID-19 pandemic, the implementation of infectious disease prevention and control policies and actions may have developed some inconvenience and difficulty in seeking medical practice and process. These characteristics (complaints) are more prominent, and timely and patient-first consideration is required immediately to build up better clinical procedures, the healthcare environment and comprehensive communication. Using the HCAT can allow health centers or health practitioners to understand the needs and demands of patients through complaints, provide friendly medical and health services, avoid unequal information transmission, build trust in doctor−patient relationships and improve patients' safety.

Mucosal immune responses induced by oral administration of recombinant Lactococcus lactis expressing the S1 protein of PDCoV.

Porcine deltacoronavirus is an evolving coronavirus that primarily infects the intestine and may lead to intestinal disease in piglets. Up to now, no commercial vaccination is readily accessible to protect against the spread of PDCoV. Lactococcus lactis has been shown to have good immune efficacy and safety and can be used as a genetically engineered vaccine to deliver antigens. In this research, we utilized L. lactis NZ9000 to provide the S1 protein orally and improved the delivery efficiency by connecting the M cell targeting ligand Co1 with the S1 protein of PDCoV in tandem to obtain the recombinant protein S1-Co1. We successfully constructed two recombinant strains capable of expressing PDCoV-S1 and PDCoV-S1-Co1 proteins (i.e., L. lactis NZ9000-S1 and L. lactis NZ9000-S1-Co1), and their immunogenic capacity was evaluated in mice. Our study shows that Lactococcus is an advantageous bacterial live vector vaccine and is anticipated as a potential PDCoV vaccination option.

HMCES protein promotes the replication of porcine epidemic diarrhea virus in Vero cells

Objective: To identify the key host protein that can regulate the replication of porcine epidemic diarrhea virus (PEDV).

The Activin/FLRG Pathway Associates with Poor COVID-19 Outcomes in Hospitalized Patients.

A subset of hospitalized COVID-19 patients, particularly the aged and those with comorbidities, develop the most severe form of the disease, characterized by acute respiratory disease syndrome (ARDS), coincident with experiencing a "cytokine storm." Here, we demonstrate that cytokines which activate the NF-κB pathway can induce activin A. Patients with elevated activin A, activin B, and FLRG at hospital admission were associated with the most severe outcomes of COVID-19, including the requirement for mechanical ventilation, and all-cause mortality. A prior study showed that activin A could decrease viral load, which indicated there might be a risk to giving COVID-19 patients an inhibitor of activin. To evaluate this, the role for activin A was examined in a hamster model of SARS-CoV-2 infection, via blockade of activin A signaling. The hamster model demonstrated that use of an anti-activin A antibody did not worsen the disease and there was no evidence for increase in lung viral load and pathology. The study indicates blockade of activin signaling may be beneficial in treating COVID-19 patients experiencing ARDS.

Structural features of an acidic polysaccharide with the potential of promoting osteoblast differentiation from Lycium ruthenicum Murr.

The enhanced osteoblast differentiation is beneficial to the prevention of osteoporosis. In this study, a homogeneous polysaccharide (LRP-S2A) with the potential of promoting osteoblast differentiation was obtained from the fruits of Lycium ruthenicum, a traditional herb for treatment of postmenopausal metabolic disorders. Structural identification indicated that LRP-S2A, with a relative molecular weight of 2.65 × 106 Da and an uronic acid content of 41.8%, contained Rha, Ara, Gal, Glc and GlcA in a molar ratio of 1.00 : 2.07 : 0.57 : 2.59 : 4.33 and was composed of a backbone consisting of 6-O-Me-α-(1→4)-D-GlcpA, 2-O-acetyl-α-(1→4)-D-Glcp, α-(1→2,4)-L-Rhap, ß-(1→3)-D-Galp andα-(1→3,5)-L-Araf, and some branches consisting of 6-O-Me-α-(1→4)-D-GlcpA and terminal α-L-Araf. These results suggested that LRP-S2A with the potential of promoting osteoblast differentiation was a new acidic polysaccharide.

The role of fibrosis index FIB-4 in predicting liver fibrosis stage and clinical prognosis: A diagnostic or screening tool?

This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.

Drug Repurposing: An Alternative Strategy to Treat COVID-19.

In order to curve the ongoing trend of the COVID-19 pandemic and save more lives, effective treatments against COVID-19 are urgently needed. Compared to developing new drugs, which may take too much time, it's more efficient and cost-effective to repurpose existing drugs in the treatment of COVID-19. Fortunately, some of the shared features of COVID-19 and other wellknown diseases make it possible to use old strategies to combat this new challenge. In this paper, we reviewed various possible strategies of drug repurposing in the treatment of COVID-19 and explored the possible scientific mechanisms behind each strategy.

Imaging findings and changes in discharged moderate novel coronavirus pneumonia patients with positive nucleic acid retest

The clinical and imaging data belonging to 52 discharged novel coronavirus pneumonia (NCP) patients with positive nucleic acid retesting results during the follow-up period were collected from the First People's Hospital, Xiaogan, Hubei Province, China, for analysis. These moderate NCP patients underwent a plain CT scan before the admission, at the time of discharge, and at re-admission due to the positive result of their COVID-19 nucleic acid retesting. The CT signs of these patients were analyzed in this study and a total of 32 (61.54%) patients presented with 123 lesions with patchy fuzzy shadows. In addition, 24 (75%) and 8 (25%) patients out of the 32 patients, had lesions distributed in both lungs and single lung, respectively. It is worth mentioning that the CT manifestations varied in discharged moderate NCP patients whose COVID-19 nucleic acid retest was positive in the follow-up period. Most patients presented with patchy fuzzy shadows and ground-glass opacity (GGO) lesions distributed in the lower lobe of both lungs. The results of the study indicated that some discharged moderate NCP patients with positive COVID-19 nucleic acid retest developed new patchy fuzzy shadows and GGO lesions. Moreover, the recurrence of NCP needs to be verified once patchy fuzzy shadows and GGO lesions appear and are not absorbed during the follow-up period. This study provided a reference for the follow-up NCP evaluation.

Limiting potential COVID-19 contagion in squatting public toilets.

BACKGROUND: Since the outbreak of the SARS-CoV-2 virus in December 2019, the COVID-19 pandemic continues to threaten global stability. Transmission of SARS-CoV-2 is mostly by respiratory droplets and direct contact but viral RNA fragments have also been detected in the faecal waste of patients with COVID-19. Cleanliness and effective sanitation of public toilets is a concern, as flushing the toilet is potentially an aerosol generating procedure. When the toilets are of the squatting type and without a cover, there exists a risk of viral contamination through the splashing of toilet water and aerosol generation. OBJECTIVE: This study aims to determine whether the cleanliness of public toilets was a concern to the general population during the COVID-19 pandemic, and whether a squatting toilet was preferred to a seated design. METHODS: A questionnaire was designed and posted on "WeChat" contact groups of the investigators. RESULTS: The survey showed that 91% of participants preferred squatting toilets, but that 72% were apprehensive of personal contamination when using public toilets. Over 63% of the respondents had encountered an incidence of water splash and would prefer public toilets to be covered during flushing and 83% of these respondents preferred a foot-controlled device. CONCLUSION: This survey suggests that consideration should be given to the installation of a simple foot-controlled device to cover public squatting toilets to help restrict potential COVID-19 contamination and to meet hygienic expectations of the public.

Analysis of viral RNA-host protein interactomes enables rapid antiviral drug discovery (preprint)

RNA viruses including SARS-CoV-2, Ebola virus (EBOV), and Zika virus (ZIKV) constitute a major threat to global public health and society. The interactions between viral genomes and host proteins are essential in the life cycle of RNA viruses and thus provide targets for drug development. However, viral RNA-host protein interactions have remained poorly characterized. Here we applied ChIRP-MS to profile the interactomes of human proteins and the RNA genomes of SARS-CoV-2, EBOV, and ZIKV in infected cells. Integrated interactome analyses revealed interaction patterns that reflect both common and virus-specific host responses, and enabled rapid drug screening to target the vulnerable host factors. We identified Enasidenib as a SARS-CoV-2 specific antiviral agent, and Trifluoperazine and Cepharanthine as broad spectrum antivirals against all three RNA viruses.

Distinct effects of asthma and COPD comorbidity on disease expression and outcome in patients with COVID-19.

BACKGROUND: The impacts of chronic airway diseases on coronavirus disease 2019 (COVID-19) are far from understood. OBJECTIVE: To explore the influence of asthma and chronic obstructive pulmonary disease (COPD) comorbidity on disease expression and outcomes, and the potential underlying mechanisms in COVID-19 patients. METHODS: A total of 961 hospitalized COVID-19 patients with a definite clinical outcome (death or discharge) were retrospectively enrolled. Demographic and clinical information were extracted from the medical records. Lung tissue sections from patients suffering from lung cancer were used for immunohistochemistry study of angiotensin-converting enzyme II (ACE2) expression. BEAS-2B cell line was stimulated with various cytokines. RESULTS: In this cohort, 21 subjects (2.2%) had COPD and 22 (2.3%) had asthma. After adjusting for confounding factors, COPD patients had higher risk of developing severe illness (OR: 23.433; 95% CI 1.525-360.135; P < .01) and acute respiratory distress syndrome (OR: 19.762; 95% CI 1.461-267.369; P = .025) than asthmatics. COPD patients, particularly those with severe COVID-19, had lower counts of CD4+ T and CD8+ T cells and B cells and higher levels of TNF-α, IL-2 receptor, IL-10, IL-8, and IL-6 than asthmatics. COPD patients had increased, whereas asthmatics had decreased ACE2 protein expression in lower airways, compared with that in control subjects without asthma and COPD. IL-4 and IL-13 downregulated, but TNF-α, IL-12, and IL-17A upregulated ACE2 expression in BEAS-2B cells. CONCLUSION: Patients with asthma and COPD likely have different risk of severe COVID-19, which may be associated with different ACE2 expression.

Self-reported Taste and Smell Disorders in Patients with COVID-19: Distinct Features in China.

Last December 2019, a cluster of viral pneumonia cases identified as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. We aimed to explore the frequencies of nasal symptoms in patients with COVID-19, including loss of smell and taste, as well as their presentation as the first symptom of the disease and their association with the severity of COVID-19. In this retrospective study, 1206 laboratory-confirmed COVID-19 patients were included and followed up by telephone one month after discharged from Tongji Hospital, Wuhan. Demographic data, laboratory values, comorbidities, symptoms, and numerical rating scale scores (0-10) of nasal symptoms were extracted from the hospital medical records, and confirmed or reevaluated by the telephone follow-up. From patients (n=1172) completing follow-up, 199 (17%) subjects had severe COVID-19 and 342 (29.2%) reported nasal symptoms. 20.6% COVID-19 patients had loss of taste (median score=6), while 11.4% had loss of smell (median score=5). Loss of taste scores, but not loss of smell scores, were significantly increased in severe vs. non-severe COVID-19 patients. Interleukin (IL)-6 and lactose dehydrogenase (LDH) serum levels were positively correlated with loss of taste scores. About 80% of COVID-19 patients recovered from smell and taste dysfunction in 2 weeks. In this cohort, only 1 out of 10 hospital admitted patients had loss of smell while 1 out of 5 reported loss of taste which was associated to severity of COVID-19. Most patients recovered smell and taste dysfunctions in 2 weeks.

Questionnaire survey on occupational exposure of health care workers working in COVID-19 isolation wards of designated hospitals in 2020

OBJECTIVE: To investigate the status of occupational exposure of health care workers working in the COVID-19 isolation wards of designated hospitals so as to take targeted measures for occupational protection. METHODS By means of convenient sampling method, a self-designed questionnaire was applied to investigate the status of occupational exposure of health care workers who supported or worked in the designated hospitals for patients with COVID-19 from Mar. 1, to Mar. 5, 2020. RESULTS: Among the 293 health care workers working in the COVID-19 isolation wards, 28.00% had occupational exposure. The skin or hair' contacting with contaminated outer surface of personal protective equipment(PPE)(65.85%) was the most common type of occupational exposure. The removal of PPE(60.98%) and the operations that may generate aerosol(47.56%) were the major links where the occupational exposure took place. After the occupational exposure occurred, 68.29% of the health care workers carried out emergency treatment, and 71.95% of the health care workers were able to report the exposure according to standard procedures. The top 3 medical operations that were most likely to cause exposure were tracheotomy, bronchoscopy and endotracheal intubation. The top 3 nursing operations that were most likely to cause occupational exposure were artificial airway nursing, sputum suction and throat swab collection. The top 3 risk factors that were most likely to cause occupational exposure of health care workers were the implementation of operations that may generate aerosol, failure to comply with disinfection and isolation system, and sudden changes in the patients' condition for emergency rescue. CONCLUSION: There are varying degrees of occupational exposure among the health care workers working in the COVID-19 isolation wards of designated hospitals. It is necessary for the management department of medical institutions to formulate practical prevention and control measures according to the high frequency types, operation links and risk factors of the occupational exposure so as to reduce the risk of occupational exposure among the health care workers.

A meta-analysis of the incidence of venous thromboembolic events and impact of anticoagulation on mortality in patients with COVID-19.

BACKGROUND: The incidence of venous thromboembolic events (VTE) in patients with COVID-19 is generally high but varies markedly. However, the relationship between anticoagulation and mortality in patients with COVID-19 is still unclear. METHODS: We performed a systematic review and meta-analysis to determine the incidence of VTE and evaluate the role of anticoagulation in patients with COVID-19. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: After a database search, 25 observational studies (20 on VTE incidence and 5 on the relationship between anticoagulation and mortality) were included. The pooled incidence rates of VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) in hospitalised COVID-19 patients were 21% (95% CI 15-27%), 15% (95% CI 10-20%), and 27% (95% CI 19-36%), respectively. A meta-analysis of five studies found that anticoagulation was not associated with an increased risk of mortality in hospitalised COVID-19 patients (RR = 0.86, 95% CI, 0.69-1.09, P = 0.218; I2 = 47.4%). CONCLUSIONS: In conclusion, the incidence of VTE among hospitalised COVID-19 patients was high. Clinical trials are urgently needed to evaluate the roles of prophylactic and therapeutic anticoagulation in COVID-19.

An Asymptomatic SARS-CoV-2-Infected Infant With Persistent Fecal Viral RNA Shedding in a Family Cluster: A Rare Case Report.

An outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become pandemic worldwide. A better understanding of asymptomatic infections is crucial to prevent and control this epidemic. Here, we report the epidemiological and clinical characteristics of a family cluster with SARS-CoV-2 infection. In the family cluster, a 32-year-old male (case 1) and a 53-year-old female (case 2, the mother-in-law of case 1) exhibited clinical symptoms of COVID-19, while case 1's 32-year-old wife (case 3) and their 11-month-old daughter (case 4) were both asymptomatic. Notably, case 4's nasopharyngeal swab samples was negative for nearly 80 days, and her immune system has been boosted for at least 57 days, but the fecal samples have tested positive for 100 days (May 13, 2020), suggesting SARS-CoV-2 may invade enterocytes and may exist in individuals with low antiviral immunity for a long term. This report highlights that asymptomatic infections should be managed with caution and vigilance. For SARS-CoV-2 testing of asymptomatic cases, besides the normally used nasopharyngeal swab, fecal sample testing is also needed.