Bioinformatics and system biology approach to identify the influences among COVID-19, ARDS and sepsis.

Background Severe coronavirus disease 2019 (COVID -19) has led to severe pneumonia or acute respiratory distress syndrome (ARDS) worldwide. we have noted that many critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. The molecular mechanisms that underlie COVID-19, ARDS and sepsis are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19, ARDS and sepsis using bioinformatics and a systems biology approach. Methods Three RNA-seq datasets (GSE171110, GSE76293 and GSE137342) from Gene Expression Omnibus (GEO) were employed to detect mutual differentially expressed genes (DEGs) for the patients with the COVID-19, ARDS and sepsis for functional enrichment, pathway analysis, and candidate drugs analysis. Results We obtained 110 common DEGs among COVID-19, ARDS and sepsis. ARG1, FCGR1A, MPO, and TLR5 are the most influential hub genes. The infection and immune-related pathways and functions are the main pathways and molecular functions of these three diseases. FOXC1, YY1, GATA2, FOXL, STAT1 and STAT3 are important TFs for COVID-19. mir-335-5p, miR-335-5p and hsa-mir-26a-5p were associated with COVID-19. Finally, the hub genes retrieved from the DSigDB database indicate multiple drug molecules and drug-targets interaction. Conclusion We performed a functional analysis under ontology terms and pathway analysis and found some common associations among COVID-19, ARDS and sepsis. Transcription factors-genes interaction, protein-drug interactions, and DEGs-miRNAs coregulatory network with common DEGs were also identified on the datasets. We believe that the candidate drugs obtained in this study may contribute to the effective treatment of COVID-19.

The Role of Self-Esteem in the Relationship Between Psychological Capital and Anxiety of Left-Behind Experience College Students During COVID-19 Pandemic: An Online Study

Background There is growing evidence that the COVID-19 pandemic has had a dramatic impact on public mental health. However, less attention has been paid to left-behind experience college students (LBEs). This online study aimed to investigate the relationship between psychological capital (PsyCap) and anxiety among LBEs during COVID-19 pandemic, and further analyze the mediation role of self-esteem between them. Methods A total of 9990 students were chosen using the stratified cluster sampling method. Three self-reported questionnaires were used to assess the PsyCap, self-esteem, and anxiety, respectively. All the statistical analyses were conducted using SPSS 23.0 and R, and to further investigate the mediation effect of self-esteem in the association of PsyCap with anxiety, AMOS 23.0 was used to build a structural equation model. Results PsyCap, self-esteem, and anxiety were significantly correlated among LBEs during the COVID-19 pandemic. PsyCap affects anxiety directly (β = –0.22, SE = 0.051, 95% CI: –0.27, –0.17, P < 0.05). In addition, self-esteem partially mediated the relationship between PsyCap and anxiety (mediating effect value = –0.16, 95% CI: –0.20, –0.13, P < 0.05). Conclusion During the pandemic of COVID-19, left-behind experience had a negative influence on the PsyCap and self-esteem of college students. In addition, for LBEs, self-esteem plays an important mediating role between PsyCap and anxiety. Therefore, from the perspective of PsyCap and self-esteem, schools should translate them into practical educational strategies to enhance the mental health and mitigate the anxiety levels of LBEs.

Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis

Coronavirus porcine epidemic diarrhea virus (PEDV) is classified in the genus Alphacoronavirus, family Coronaviridae that encodes the only accessory protein, ORF3 protein. However, how ORF3 contributes to viral pathogenicity, adaptability, and replication is obscure. In this review, we summarize current knowledge and identify gaps in many aspects of ORF3 protein in PEDV, with emphasis on its unique biological features, including membrane topology, Golgi retention mechanism, potential intrinsic disordered property, functional motifs, protein glycosylation, and codon usage phenotypes relate to genetic evolution and gene expression. In addition, we propose intriguing questions related to ORF3 protein that we hope to stimulate further studies and encourage collaboration among virologists worldwide to provide constructive knowledge about the unique characteristics and biological functions of ORF3 protein, by which their potential role in clarifying viral behavior and pathogenesis can be possible. Graphical abstract

mRNA therapeutics for disease therapy: principles, delivery, and clinical translation.

Messenger RNA (mRNA) has become a key focus in the development of therapeutic agents, showing significant potential in preventing and treating a wide range of diseases. The COVID-19 pandemic in 2020 has accelerated the development of mRNA nucleic therapeutics and attracted significant investment from global biopharmaceutical companies. These therapeutics deliver genetic information into cells without altering the host genome, making them a promising treatment option. However, their clinical applications have been limited by issues such as instability, inefficient in vivo delivery, and low translational efficiency. Recent advances in molecular design and nanotechnology have helped overcome these challenges, and several mRNA formulations have demonstrated promising results in both animal and human testing against infectious diseases and cancer. This review provides an overview of the latest research progress in structural optimization strategies and delivery systems, and discusses key considerations for their future clinical use.

Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis.

Coronavirus porcine epidemic diarrhea virus (PEDV) is classified in the genus Alphacoronavirus, family Coronaviridae that encodes the only accessory protein, ORF3 protein. However, how ORF3 contributes to viral pathogenicity, adaptability, and replication is obscure. In this review, we summarize current knowledge and identify gaps in many aspects of ORF3 protein in PEDV, with emphasis on its unique biological features, including membrane topology, Golgi retention mechanism, potential intrinsic disordered property, functional motifs, protein glycosylation, and codon usage phenotypes related to genetic evolution and gene expression. In addition, we propose intriguing questions related to ORF3 protein that we hope to stimulate further studies and encourage collaboration among virologists worldwide to provide constructive knowledge about the unique characteristics and biological functions of ORF3 protein, by which their potential role in clarifying viral behavior and pathogenesis can be possible.

Diagnostic accuracy of autoverification and guidance system for COVID-19 RT-PCR results.

Background: To date, most countries worldwide have declared that the pandemic of COVID-19 is over, while the WHO has not officially ended the COVID-19 pandemic, and China still insists on the personalized dynamic COVID-free policy. Large-scale nucleic acid testing in Chinese communities and the manual interpretation for SARS-CoV-2 nucleic acid detection results pose a huge challenge for labour, quality and turnaround time (TAT) requirements. To solve this specific issue while increase the efficiency and accuracy of interpretation, we created an autoverification and guidance system (AGS) that can automatically interpret and report the COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results relaying on computer-based autoverification procedure and then validated its performance in real-world environments. This would be conductive to transmission risk prediction, COVID-19 prevention and control and timely medical treatment for positive patients in the context of the predictive, preventive and personalized medicine (PPPM). Methods: A diagnostic accuracy test was conducted with 380,693 participants from two COVID-19 test sites in China, the Hong Kong Hybribio Medical Laboratory (n = 266,035) and the mobile medical shelter at a Shanghai airport (n = 114,658). These participants underwent SARS-CoV-2 RT-PCR from March 28 to April 10, 2022. All RT-PCR results were interpreted by laboratorians and by using AGS simultaneously. Considering the manual interpretation as gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were applied to evaluate the diagnostic value of the AGS on the interpretation of RT-PCR results. Results: Among the 266,035 samples in Hong Kong, there were 16,356 (6.15%) positive, 231,073 (86.86%) negative, 18,606 (6.99%) indefinite, 231,073 (86.86%, negative) no retest required and 34,962 (13.14%, positive and indefinite) retest required; the 114,658 samples in Shanghai consisted of 76 (0.07%) positive, 109,956 (95.90%) negative, 4626 (4.03%) indefinite, 109,956 (95.90%, negative) no retest required and 4702 (4.10%, positive and indefinite) retest required. Compared to the fashioned manual interpretation, the AGS is a procedure of high accuracy [99.96% (95%CI, 99.95-99.97%) in Hong Kong and 100% (95%CI, 100-100%) in Shanghai] with perfect sensitivity [99.98% (95%CI, 99.97-99.98%) in Hong Kong and 100% (95%CI, 100-100%) in Shanghai], specificity [99.87% (95%CI, 99.82-99.90%) in Hong Kong and 100% (95%CI, 99.92-100%) in Shanghai], PPV [99.98% (95%CI, 99.97-99.99%) in Hong Kong and 100% (95%CI, 99.99-100%) in Shanghai] and NPV [99.85% (95%CI, 99.80-99.88%) in Hong Kong and 100% (95%CI, 99.90-100%) in Shanghai]. The need for manual interpretation of total samples was dramatically reduced from 100% to 13.1% and the interpretation time fell from 53 h to 26 min in Hong Kong; while the manual interpretation of total samples was decreased from 100% to 4.1% and the interpretation time dropped from 20 h to 16 min at Shanghai. Conclusions: The AGS is a procedure of high accuracy and significantly relieves both labour and time from the challenge of large-scale screening of SARS-CoV-2 using RT-PCR. It should be recommended as a powerful screening, diagnostic and predictive system for SARS-CoV-2 to contribute timely the ending of the COVID-19 pandemic following the concept of PPPM.

Viral contamination on the surfaces of the personal protective equipment among health care professionals working in COVID-19 wards: A single-center prospective, observational study.

OBJECTIVE: To evaluate potential viral contamination on the surfaces of personal protective equipment (PPE) in COVID-19 wards. METHODS: Face shields, gloves, the chest area of PPE and shoe soles were sampled at different time points. The samples were tested for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR, and the cycle threshold (CT) values were recorded. RESULTS: The positive rate was 74.7% (239/320) for all PPE specimens. The CT values of the samples were ranked in the following order: face shields > chests > gloves > shoe soles (37.08±1.38, 35.48±2.02, 34.17±1.91 and 33.52±3.16, respectively; P for trend < .001). After disinfection, the CT values of shoe soles decreased compared with before disinfection (32.78±3.47 vs. 34.3±2.61, P = .037), whereas no significant effect of disinfection on the CT values of face shields, chests and gloves was observed. After disinfection, the CT values of specimens collected from shoe soles gradually increased; before disinfection, the CT values of shoe sole specimens were all less than 35. CONCLUSIONS: SARS-CoV-2 can attach to the surfaces of the PPE of healthcare professionals in COVID-19 wards, especially the shoe soles and undisinfected gloves. Shoe soles had the highest SARS-CoV-2 loads among all tested PPE items.

Three Amino Acid Substitutions in the Spike Protein Enable the Coronavirus Porcine Epidemic Diarrhea Virus To Infect Vero Cells.

Porcine epidemic diarrhea virus (PEDV), a continuously evolving pathogen, causes severe diarrhea in piglets, with high mortality rates. To prevent or mitigate the disease, it is common practice to develop live or inactivated PEDV vaccines based on cell-adapted viral variants. Propagating wild-type PEDV in cultured cells is, however, often challenging due to the lack of knowledge about the requirements for the cell adaptation of PEDV. In the present study, by using the RNA-targeted reverse genetic system for PEDV to apply S protein swapping followed by the rescue of the recombinant viruses, three key amino acid mutations in the S protein, A605E, E633Q, and R891G, were identified, which enable attenuated PEDV strain DR13 (DR13att) to efficiently and productively infect Vero cells, in contrast to the parental DR13 strain (DR13par). The former two key mutations reside inside and in the vicinity of the receptor binding domain (RBD), respectively, while the latter occurs at the N-terminal end of the fusion peptide (FP). Besides the three key mutations, other mutations in the S protein further enhanced the infection efficiency of the recombinant viruses. We hypothesize that the three mutations changed PEDV tropism by altering the S2' cleavage site and the RBD structure. This study provides basic molecular insight into cell adaptation by PEDV, which is also relevant for vaccine design. IMPORTANCE Porcine epidemic diarrhea virus (PEDV) is a lethal pathogen for newborn piglets, and an efficient vaccine is needed urgently. However, propagating wild-type PEDV in cultured cells for vaccine development is still challenging due to the lack of knowledge about the mechanism of the cell adaptation of PEDV. In this study, we found that three amino acid mutations, A605E, E633Q, and R891G, in the spike protein of the Vero cell-adapted PEDV strain DR13att were critical for its cell adaptation. After analyzing the mutation sites in the spike protein, we hypothesize that the cell adaptation of DR13att was achieved by altering the S2' cleavage site and the RBD structure. This study provides new molecular insight into the mechanism of PEDV culture adaptation and new strategies for PEDV vaccine design.

Clinical characteristics, risk factors and outcomes of cancer patients with COVID-19: A population-based study.

INTRODUCTION: Cancer patients may be susceptible to poorer outcomes in COVID-19 infection owing to the immunosuppressant effect of chemotherapy/radiotherapy and cancer growth, along with the potential for nosocomial transmission due to frequent hospital admissions. METHODS: This was a population-based retrospective cohort study of COVID-19 patients who presented to Hong Kong public hospitals between 1 January 2020 and 8 December 2020. The primary outcome was a composite endpoint of requirement for intubation, ICU admission and 30-day mortality. RESULTS: The following study consisted of 6089 COVID-19 patients (median age 45.9 [27.8.1-62.7] years; 50% male), of which 142 were cancer subjects. COVID-19 cancer patients were older at baseline and tended to present with a higher frequency of comorbidities, including diabetes mellitus, hypertension, chronic obstructive pulmonary disease, ischemic heart disease, ventricular tachycardia/fibrillation and gastrointestinal bleeding (p < 0.05). These subjects also likewise tended to present with higher serum levels of inflammatory markers, including D-dimer, lactate dehydrogenase, high sensitivity troponin-I and C-reactive protein. Multivariate Cox regression showed that any type of cancer presented with an almost four-fold increased risk of the primary outcome (HR: 3.77; 95% CI: 1.63-8.72; p < 0.002) after adjusting for significant demographics, Charlson comorbidity index, number of comorbidities, past comorbidities and medication history. This association remained significant when assessing those with colorectal (HR: 5.07; 95% CI: 1.50-17.17; p < 0.009) and gastrointestinal malignancies (HR: 3.79; 95% CI: 1.12-12.88; p < 0.03), but not with lung, genitourinary, or breast malignancies, relative to their respective cancer-free COVID-19 counterparts. CONCLUSIONS: COVID-19 cancer patients are associated with a significantly higher risk of intubation, ICU admission and/or mortality.

Safety of primary immunization using inactivated SARS-CoV-2 vaccine (CoronaVac®) among population aged 3 years and older in a large-scale use: A multi-center open-label study in China.

OBJECTIVE: To evaluate the safety of primary immunization using CoronaVac® among population aged 3 years and above in a large-scale use. METHOD: A multi-center open-label study was carried out in 11 provinces of China. Individuals aged 3 years and older who had no history of COVID-19 vaccination or had received only one dose of CoronaVac® were enrolled in this study. Adults and elderly with or without underlying medical conditions(UMCs) were also recruited. Eligible participants received one or two doses of CoronaVac® with an interval of 28 days. Demographic information, vaccination and the occurrence of adverse events were recorded by participants or guardians using data collection system designed for this study. All adverse events occurred within 6 months after the second dose of vaccination were collected. The incidence of adverse events that cannot be ruled out as being caused by the vaccine were calculated to assess the safety of CoronaVac®. This study is registered with ClinicalTrials. Gov (NCT04911790 and NCT04992208). RESULTS: A total of 162,691 participants have been included in this study and 89.50 % had finished primary immunization. Among adults and elderly, people with UMCs accounted for 25.85 %, with the top five disease being hypertension, diabetes, chronic gastritis, coronary heart disease(CHD) and kidney stone. The overall incidence of adverse reactions (ARs) within 6 months after the second vaccination was 2.70 %, with incidence for children and adolescents, adults, and elderly being 2.03 %, 3.46 %, and 1.90 %, respectively. Most ARs were mild (grade 1). Pain at the injection sites, fatigue, induration/swelling, and headache were the most common symptoms, occurring in 1.64 %, 0.46 %, 0.31 % and 0.24 %, respectively. No serious adverse events related to vaccines were reported. No adverse events of special interest (AESIs) were identified. For children and adolescents, children aged 3-5 years had the highest incidence of ARs of 3.29 %. The incidence of ARs among those aged 18 years and older with and without UMCs were 2.81 % and 2.99 %, respectively, with no statistical significance between two groups(P = 0.089). And people with coronary heart disease had higher AR incidence compared to those with other UMCs, but the most common symptoms was pain at the injection site. CONCLUSION: CoronaVac® is safe in a large-scale use and shows well-tolerance for children and adolescents and people with underlying medical conditions. Further studies need to be conducted to explore the relation of ARs incidence to age or different kinds of UMCs.

It is time to improve the acceptance of COVID-19 vaccines among people with chronic diseases: A systematic review and meta-analysis.

This study aims to investigated COVID-19 vaccine acceptance among people with chronic diseases and the factors correlating with their vaccination hesitancy. The articles were searched in PubMed, Ovid, EMBASE, and web of science databases between December 2019 and October 2022. Cross-sectional studies, including the acceptance of the COVID-19 vaccine by patients with chronic diseases (≥18 years old), were included in this study. The outcomes included the proportion and 95% confidence interval (95% CI) of chronic disease patients willing to be vaccinated and the odds ratio (OR) and 95% CI of correlating factors. The source of heterogeneity was analyzed through meta-regression and subgroup analysis. We included 31 studies involving 57 875 patients with chronic disease. The overall COVID-19 vaccine acceptance among patients with chronic disease was 0.65 (95% CI, 0.59-0.72). The acceptance among the elderly patients was 0.53 (95% CI, 0.26-0.80). South America had the highest COVID-19 vaccine acceptance rate and Asia the lowest, while on a country level, the United Kingdom had the highest acceptance rate among patients with chronic diseases. People with rheumatic immune diseases had the lowest rate of COVID-19 vaccine acceptance. Concerns about vaccine safety had a statistically different effect on acceptance. Overall, the health systems ought to focus on educating specific groups of individuals on the benefits of COVID-19 vaccination and addressing safety concerns.

Microfluidic chip and isothermal amplification technologies for the detection of pathogenic nucleic acid.

The frequency of outbreaks of newly emerging infectious diseases has increased in recent years. The coronavirus disease 2019 (COVID-19) outbreak in late 2019 has caused a global pandemic, seriously endangering human health and social stability. Rapid detection of infectious disease pathogens is a key prerequisite for the early screening of cases and the reduction in transmission risk. Fluorescence quantitative polymerase chain reaction (qPCR) is currently the most commonly used pathogen detection method, but this method has high requirements in terms of operating staff, instrumentation, venues, and so forth. As a result, its application in the settings such as poorly conditioned communities and grassroots has been limited, and the detection needs of the first-line field cannot be met. The development of point-of-care testing (POCT) technology is of great practical significance for preventing and controlling infectious diseases. Isothermal amplification technology has advantages such as mild reaction conditions and low instrument dependence. It has a promising prospect in the development of POCT, combined with the advantages of high integration and portability of microfluidic chip technology. This study summarized the principles of several representative isothermal amplification techniques, as well as their advantages and disadvantages. Particularly, it reviewed the research progress on microfluidic chip-based recombinase polymerase isothermal amplification technology and highlighted future prospects.

Ultrasensitive NO Sensor Based on a Nickel Single-Atom Electrocatalyst for Preliminary Screening of COVID-19.

A new coronavirus, SARS-CoV-2, has caused the coronavirus disease-2019 (COVID-19) epidemic. A rapid and economical method for preliminary screening of COVID-19 may help to control the COVID-19 pandemic. Here, we report a nickel single-atom electrocatalyst that can be printed on a paper-printing sensor for preliminary screening of COVID-19 suspects by efficient detection of fractional exhaled nitric oxide (FeNO). The FeNO value is confirmed to be related to COVID-19 in our exploratory clinical study, and a machine learning model that can accurately classify healthy subjects and COVID-19 patients is established based on FeNO and other features. The nickel single-atom electrocatalyst consists of a single nickel atom with N2O2 coordination embedded in porous acetylene black (named Ni-N2O2/AB). A paper-printed sensor was fabricated with the material and showed ultrasensitive response to NO in the range of 0.3-180 ppb. This ultrasensitive sensor could be applied to preliminary screening of COVID-19 in everyday life.

Computational analysis of interior mutations of SARS-CoV-2 Spike protein suggest a balance of protein stability and S2: S1 separation propensity.

SARS-CoV-2 variants often include surface mutations in the Spike protein that are important for viruses to recognize host receptors and evade antibody neutralization. The Spike protein also has mutations in the interior of the protein likely to affect the Spike protein S1 - S2 subunit's separation propensity, the most important of which is the D614G mutation. Remarkably, the Omicron variant contains a large number of internal mutations at the S2: S1 interface, which have not been investigated yet. In this study, we examined the effects of such interfacial mutations on the S2: S1 and subunit domain interactions and on the subunit's dissociation process. We found that the interaction with S2 is mainly contributed by the three encapsulation domains, named INT, ED1 and ED2 of S1, which are sandwiched between the S1 RBD and N-terminal NTD domain. We found that D614 is the strongest contributor for the S2: S1 interaction which is greatly weakened by the D614G mutation. Surprisingly, we found that, mutations T547K, H655Y, N764K, N856K, N969K, L981F in the Omicron variant largely enhance the S2: ED1 interaction, partially compensating the loss of S2: ED2 interaction due to the D614G mutation. Lastly, these results, together with biological considerations, allow us to suggest that in addition to the binding strength of between the RBD and ACE2, the stability of the Spike protein and the propensity of Spike protein S2: S1 separation are critical factors which likely exist in a balance for a particular infectivity and pathogenicity of the virus.

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells.

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease.

Acute kidney injury and its association with mortality in Asian COVID-19 patients: A meta-analysis.

BACKGROUND: Previous evidence suggests that acute kidney injury (AKI) is common in patients with COVID-19 and associated with adverse outcomes. Moreover, the incidence and mortality of AKI in Asia are ambiguous. OBJECTIVE: Evaluating the risk factors and risk of death from AKI in -COVID-19 patients in Asia. MATERIALS AND METHODS: We conducted a meta-analysis of clinical observational studies of -COVID-19 patients in Asia. Outcome measures included: AKI in COVID-19 patients, overall mortality in COVID-19 patients, and mortality assessment in patients with AKI. The random-effects model was adopted, with heterogeneity and sensitivity analysis. RESULTS: 27 clinical studies (18,216 Asian patients with COVID-19) have been included in the study. The pooled incidence of AKI was 0.19 (95% CI 16 - 23%; I2 = 98.9%, p < 0.001); the pooled incidence of total mortality was 0.19 (95% CI 17 - 22%; I2 = 98.9%, p < 0.001). No publication bias was found (Egger's test, p = 0.396, 0.213). The pooled mortality in AKI patients with COVID-19 was 50% (95% CI 33 - 67%; I2 by random-effects model = 98.4%, p < 0.001). AKI was found to be a risk factor for death in stepwise regression analysis; age, diabetes, and hypertension were influencing factors for AKI risk in -COVID-19 patients. CONCLUSION: AKI is a common complication in Asian COVID-19 patients, and it is associated with an increase in mortality of Asian COVID-19 patients. Any treatment that protects the kidney may be a practical intervention to reduce the mortality of COVID-19 patients in Asia.

Antigenicity Alternations of Variant PEDV S Protein Disclosed by Linear B Cell Epitope Mapping.

The spike protein (S) plays a crucial role in porcine epidemic diarrhea virus (PEDV) infection and induces neutralizing antibodies. Mutations of the S protein are supposed to provide the main antigenic shift leading to the antigenic escape of PEDVs. It is therefore a significant question how much accumulation of antigenic shift could lead to the antigenic escape of the variant PEDV. To provide an answer in the study, B cell epitopes (BCEs) on the S protein of the PEDV vaccine strain CV777 (SCV777) and variant strain SD2014 (SSD2014) were mapped using biosynthetic peptides and rabbit anti-PEDV S serum. Seventy-nine and 68 linear BCEs were identified from SCV777 and SSD2014, respectively. While 66.2% of the BCEs of SSD2014 could be recognized by anti-SCV777 serum and 67.1% of SCV777 BCEs could be recognized by anti-SSD2014 serum, more than 40% of the BCEs identified using anti-SCV777 serum on SCV777 could not be recognized by anti-SSD2014 serum and vice versa. The completely shared BCEs took low percentages of 29.4% and 25.3% for SSD2014 and SCV777, respectively. These results indicate a low conservation of antigenicity of the S protein compared to a relatively high amino acid sequence similarity of 92.2% between the two strains. The study provided a BCE shift reference of PEDV antigenic escape and surveillance control.

An external quality assessment for the molecular testing of the SARS-CoV-2 virus genome in Zhejiang Province, China.

The COVID-19 pandemic has necessitated the rapid expansion of laboratories that conduct SARS-CoV-2 tests. A provincial external quality assessment (EQA) scheme on SARS-CoV-2 tests was organized by Zhejiang Provincial CDC to assess the accuracy of the tests in individual CDC municipal and county laboratories in Zhejiang Province, China. Three positive samples in high, medium, and low concentrations, respectively, were prepared using the serial dilutions from the culture with the viral titer concentration of 1×106.3 TCID50/mL, and one negative sample were included. A total of 93 laboratories participated, contributing results from 36 distinct combinations of nucleic acid extraction methods and PCR reagents. There was 100% concordance among all laboratories for all EQA samples, and no false-positive or false-negative results were observed. The EQA survey provides confidence in the identification of infected individuals or asymptomatic populations and assurance for clinical and public health decision-making based on test results.

Bis-Benzylisoquinoline Alkaloids Inhibit Porcine Epidemic Diarrhea Virus In Vitro and In Vivo.

Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae that causes severe diarrhea and high mortality in neonatal suckling piglets. Currently, there is no effective medication against this pathogen. Cepharanthine (CEP), tetrandrine (TET), and fangchinoline (FAN) are natural bis-benzylisoquinoline alkaloids with anti-inflammatory, antitumor, and antiviral properties. Here, we first found that CEP, TET, and FAN had anti-PEDV activity with IC50 values of 2.53, 3.50, and 6.69 µM, respectively. The compounds could block all the processes of viral cycles, but early application of the compounds before or during virus infection was advantageous over application at a late stage of virus replication. FAN performed inhibitory function more efficiently through interfering with the virus entry and attachment processes or through attenuating the virus directly. CEP had a more notable effect on virus entry. With the highest SI index of 11.8 among the three compounds, CEP was chosen to carry out animal experiments. CEP in a safe dosage of 11.1 mg/kg of body weight could reduce viral load and pathological change of piglet intestinal tracts caused by PEDV field strain challenge, indicating that CEP efficiently inhibited PEDV infection in vivo. All of these results demonstrated that the compounds of bis-benzylisoquinoline alkaloids could inhibit PEDV proliferation efficiently and had the potential of being developed for PED prevention and treatment.