The characteristics and predictive role of lymphocyte subsets in COVID-19 patients.

OBJECTIVE: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients. METHOD: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients, and analyzed their potential impacts on COVID-19 outcomes. RESULTS: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe disease, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+, and CD4+ T cells at admission. CONCLUSION: Our study showed that total, CD8+, and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. Lower T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.

Potent immunogenicity and broad-spectrum protection potential of microneedle array patch-based COVID-19 DNA vaccine candidates encoding dimeric RBD chimera of SARS-CoV and SARS-CoV-2 variants.

Breakthrough infections by SARS-CoV-2 variants pose a global challenge to COVID-19 pandemic control, and the development of more effective vaccines of broad-spectrum protection is needed. In this study, we constructed pVAX1-based plasmids encoding receptor-binding domain (RBD) chimera of SARS-CoV-1 and SARS-CoV-2 variants, including pAD1002 (encoding RBDSARS/BA1), pAD1003 (encoding RBDSARS/Beta) and pAD131 (encoding RBDBA1/Beta). Plasmids pAD1002 and pAD131 were far more immunogenic than pAD1003 in terms of eliciting RBD-specific IgG when intramuscularly administered without electroporation. Furthermore, dissolvable microneedle array patches (MAP) greatly enhanced the immunogenicity of these DNA constructs in mice and rabbits. MAP laden with pAD1002 (MAP-1002) significantly outperformed inactivated SARS-CoV-2 virus vaccine in inducing RBD-specific IFN-γ+ effector and memory T cells, and generated T lymphocytes of different homing patterns compared to that induced by electroporated DNA in mice. In consistence with the high titer neutralization results of MAP-1002 antisera against SARS-CoV-2 pseudoviruses, MAP-1002 protected human ACE2-transgenic mice from Omicron BA.1 challenge. Collectively, MAP-based DNA constructs encoding chimeric RBDs of SARS-CoV-1 and SARS-CoV-2 variants, as represented by MAP-1002, are potential COVID-19 vaccine candidates worthy further translational study.

Will Alibaba's additional financial service contribute to sellers' satisfaction and loyalty during the pandemic? Evidence from Taobao sellers

Electronic commerce (e-commerce) has shown dramatic growth in recent decades, and sellers on e-commerce platforms have also been affected by the global COVID-19 pandemic. By collecting data from 313 Taobao sellers, we investigated the relationships among e-commerce platform additional financial service quality, sellers' satisfaction, and loyalty to the platform, as well as the moderating roles of sellers' financial pressure during the pandemic and perceived COVID-19 government financial support in the satisfaction-loyalty relationship. Our results show that better financial service quality enhances sellers' satisfaction with the platform, which in turn translates into platform loyalty. We also evidence the moderating effects of COVID-related financial pressure and sellers' perception of COVID-related government financial relief policy on the satisfaction-loyalty relationship. Our research makes potential contributions to the e-commerce field and provides timely guidance for e-commerce practice in the pandemic period.

Impact of the COVID-19 pandemic on cardiac implantable electronic device implantation in China: Insights from 2 years of changing pandemic conditions

Background A substantial reduction in the number of cardiac implantable electronic device (CIED) implantation was reported in the early stages of the COVID-19 pandemic. None of the studies have yet explored changes in CIED implantation during the following pandemic. Objective To explore changes in CIED implantation during the COVID-19 pandemic from 2020 to 2021. Methods From 2019 to 2021, 177,263 patients undergone CIED implantation from 1,227 hospitals in China were included in the analysis. Generalized linear models measured the differences in CIED implantation in different periods. The relationship between changes in CIED implantation and COVID-19 cases was assessed by simple linear regression models. Results Compared with the pre-COVID-19 period, the monthly CIED implantation decreased by 17.67% (95% CI: 16.62–18.72%, p < 0.001) in 2020. In 2021, the monthly number of CIED implantation increased by 15.60% (95% CI: 14.34–16.85%, p < 0.001) compared with 2020. For every 10-fold increase in the number of COVID-19 cases, the monthly number of pacemaker implantation decreased by 429 in 2021, while it decreased by 676 in 2020. The proportion of CIED implantation in secondary medical centers increased from 52.84% in 2019 to 56.77% in 2021 (p < 0.001). For every 10-fold increase in regional accumulated COVID-19 cases, the proportion of CIED implantation in secondary centers increased by 6.43% (95% CI: 0.47–12.39%, p = 0.036). Conclusion The impact of the COVID-19 pandemic on the number of CIED implantation is diminishing in China. Improving the ability of secondary medical centers to undertake more operations may be a critical way to relieve the strain on healthcare resources during the epidemic.

Impact of the COVID-19 on electricity consumption of open university campus buildings - The case of Twente University in the Netherlands.

Since the COVID-19 outbreak, the restrictive policies enacted by countries in response to the epidemic have led to changes in the movement of people in public places, which has had a direct impact on the use and energy consumption of various public buildings. This study was based on electricity consumption data for 25 on-campus public buildings at 1-hour intervals between January 2020 and June 2022 at Tewnte University in the Netherlands, and after the data were climate-corrected by multiple regression analysis, the changes in EU and EUI for various types of buildings were compared for different restriction periods using ANOVA, LSD and t-tests. And additionally, further analyzed the changes and reasons for the electricity consumption of various public buildings on campus and customers' electricity consumption behavior in a period of time after the lifting of the epidemic restriction policy. The results of ANOVA analysis show that the restriction policy has a significant effect on teaching, sports, and cultural buildings, and the electricity intensity of the three types of buildings is reduced by 0.28, 0.09, and 0.07 kwh/m2/day respectively under the strict restriction policy; The t-test results show that during the restriction period, all building types, except for living and academic buildings, show a significant decreasing trend, with the teaching buildings having the greatest energy saving potential, with an average daily EU reduction of 1088kwh/day and an EUI reduction of 0.075kwh/ m2/day. The above findings provide a case study of a complete cycle of energy consumption changes in university buildings under similar epidemic restriction policies before and after the epidemic restriction, and inform the electricity allocation policies of university and government energy management authorities.

Will Alibaba’s additional financial service contribute to sellers’ satisfaction and loyalty during the pandemic? Evidence from Taobao sellers

Electronic commerce (e-commerce) has shown dramatic growth in recent decades, and sellers on e-commerce platforms have also been affected by the global COVID-19 pandemic. By collecting data from 313 Taobao sellers, we investigated the relationships among e-commerce platform additional financial service quality, sellers' satisfaction, and loyalty to the platform, as well as the moderating roles of sellers' financial pressure during the pandemic and perceived COVID-19 government financial support in the satisfaction-loyalty relationship. Our results show that better financial service quality enhances sellers' satisfaction with the platform, which in turn translates into platform loyalty. We also evidence the moderating effects of COVID-related financial pressure and sellers' perception of COVID-related government financial relief policy on the satisfaction-loyalty relationship. Our research makes potential contributions to the e-commerce field and provides timely guidance for e-commerce practice in the pandemic period.

A megadiverse naïve library derived from numerous camelids for efficient and rapid development of VHH antibodies.

The field of antibody development is under pressure to meet rising demands for speed, cost-effectiveness, efficacy, reliability, and large-scale production. It is costly and time-consuming to immunize animals and build a single-domain antibody (sdAb) library for each target. Using the variable domain (VHH) of heavy-chain only antibodies (HcAbs) derived from blood samples of 75 non-immunized camelid animals (51 alpacas, 13 llamas, 11 Bactrian camels), and spleens from two Bactrian camels, a naïve sdAb library with extensive megadiversity and reusability was constructed. The library was evaluated using next-generation DNA sequencing (NGS) and was found to contain hundreds of billions of unique clones. To confirm the availability of target-specific VHHs, a naive library was screened for a variety of targets. At least two VHH candidates were extracted for each target using a 20-day selection pipeline. Some binders had ultrahigh potencies, with binding affinities in the nanomolar range. This naïve library, in particular, offers the possibility of acquiring unique antibodies targeting antigens of interest with low feasible dissociation constant (kD) without the time, effort, and price associated in producing antibodies in animals via antigen injection. Overall, the study shows that the megadiverse naïve library provides a rapid, adaptable, and easy platform for antibody creation, emphasizing its therapeutic and diagnostic implications.

Antiviral Drugs Screening for Swine Acute Diarrhea Syndrome Coronavirus.

Coronaviruses as possible cross-species viruses have caused several epidemics. The ongoing emergency of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has posed severe threats to the global economy and public health, which has generated great concerns about zoonotic viruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), an alpha-coronavirus, was responsible for mass piglet deaths, resulting in unprecedented economic losses, and no approved drugs or vaccines are currently available for SADS-CoV infection. Given its potential ability to cause cross-species infection, it is essential to develop specific antiviral drugs and vaccines against SADS-CoV. Drug screening was performed on a total of 3523 compound-containing drug libraries as a strategy of existing medications repurposing. We identified five compounds (gemcitabine, mycophenolate mofetil, mycophenolic acid, methylene blue and cepharanthine) exhibiting inhibitory effects against SADS-CoV in a dose-dependent manner. Cepharanthine and methylene blue were confirmed to block viral entry, and gemcitabine, mycophenolate mofetil, mycophenolic acid and methylene blue could inhibit viral replication after SADS-CoV entry. This is the first report on SADS-CoV drug screening, and we found five compounds from drug libraries to be potential anti-SADS-CoV drugs, supporting the development of antiviral drugs for a possible outbreak of SADS-CoV in the future.

Anxiety and sleep quality among front-line nurses treating first wave COVID-19 in China: The mediating role of mindfulness.

AIM: To explore anxiety, sleep quality, and mindfulness of frontline nurses at the initial epicenter of the pandemic, to examine the mediating effects of mindfulness. BACKGROUND: COVID-19 was first identified in Wuhan, China in January 2020. Nurses were at the forefront of care and treatment across hospitals in response to the pandemic. METHODS: Single site cross-sectional survey conducted in Wuhan province (China) between March and April in 2020. Quantitative analysis of survey data from N118 nurses working in the frontline COVID response. Questionnaires included: The general information questionnaire, the Self-Anxiety Scale, the Short Inventory of Mindfulness, and the Pittsburgh Sleep Quality Index. RESULTS: Front-line nurses' anxiety was positively associated with sleep quality and mindfulness was negatively associated with anxiety and sleep quality. Mindfulness had a mediating role on anxiety and sleep quality, with intermediary adjustment effects (ES = 0.136, 95 % CI 0.02 to 0.26), accounting for 21.9 % of the total effect ratio. CONCLUSIONS: Anxiety causes a reduction in sleep quality and mindfulness can help with anxiety. Mindfulness strategies may help during periods of higher anxiety in the workplace; however, other factors must be considered. Further research is required on strategies for assisting nurses during periods of extreme anxiety.

The Application of Polycaprolactone Scaffolds with Poly(ε-caprolactone)-Poly(ethylene glycol)-Poly(ε-caprolactone) Loaded on Kidney Cell Culture.

Human embryonic kidney cells are the host of adenovirus type-5 (Ad5) amplification. An Ad5-vector-based COVID-19 vaccine has been proven to be tolerated and immunogenic in healthy adults. Therefore, a rationally designed scaffold for culturing human embryonic kidney cells is useful for further studying its mechanism of action. Herein, a three-dimensional layered reticulated polycaprolactone (PCL) scaffold coated with poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCEC) was developed to proliferate human embryonic kidney cells and to be used to amplify the Ad5 vector. The results indicate that PCEC improves the hydrophilicity and the cell culture ability of PCL cell culture scaffolds, resulting in a three times higher cell proliferation ratio of human embryonic kidney cells compared with those grown on bare PCL cell culture scaffolds. Meanwhile, the cytotoxicity test results showed that the scaffold material is noncytotoxic. This work provides an effective and scalable method for the in-depth study of adenoviruses.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

Non-viral vectors for RNA delivery.

RNA-based therapy is a promising and potential strategy for disease treatment by introducing exogenous nucleic acids such as messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides (ASO) to modulate gene expression in specific cells. It is exciting that mRNA encoding the spike protein of COVID-19 (coronavirus disease 2019) delivered by lipid nanoparticles (LNPs) exhibits the efficient protection of lungs infection against the virus. In this review, we introduce the biological barriers to RNA delivery in vivo and discuss recent advances in non-viral delivery systems, such as lipid-based nanoparticles, polymeric nanoparticles, N-acetylgalactosamine (GalNAc)-siRNA conjugate, and biomimetic nanovectors, which can protect RNAs against degradation by ribonucleases, accumulate in specific tissue, facilitate cell internalization, and allow for the controlled release of the encapsulated therapeutics.

The effect of urban morphological characteristics on the spatial variation of PM2.5 air quality in downtown Nanjing.

The effects of the urban morphological characteristics on the spatial variation of near-surface PM2.5 air quality were examined. Unlike previous studies, we performed the analyses in real urban environments using continuous observations covering the whole scale of urban densities typically found in cities. We included data from 31 measurement stations divided into 8 different wind sectors with individually defined morphological characteristics leading to highly varying urban characteristics. The urban morphological characteristics explained up to 73% of the variance in normalized PM2.5 concentrations in street canyons, indicating that the spatial variation of the near-surface PM2.5 air quality was mostly defined by the characteristics studied. The fraction of urban trees nearby the stations was found to be the most important urban morphological characteristic in explaining the PM2.5 air quality, followed by the height-normalized roughness length as the second important parameter. An increase in the fraction of trees within 50 m of the stations from 25 percentile to 75 percentile (i.e. by the interquartile range, IQR) increased the normalized PM2.5 concentration by up to 24% in the street canyons. In open areas, an increase in the trees by the IQR actually decreased the normalized PM2.5 by 6% during the pre-COVID period. An increase in the height-normalized roughness length by the IQR increased the normalized PM2.5 by 9% in the street canyons. The results obtained in this study can help urban planners to identify the key urban characteristics affecting the near-surface PM2.5 air quality and also help researchers to evaluate how representative the existing measurement stations are compared to other parts of the cities.

Understanding the Secret of SARS-CoV-2 Variants of Concern/Interest and Immune Escape.

The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape.

The risk factors for severe patients with COVID-19 in China: A systematic review and meta-analysis

COVID-19 is spreading exponentially. In order to optimize medical resources allocation and reduce mortality, biomarkers are needed to differentiate between COVID-19 patients with or without severe diseases early as possible. We searched Ovid MEDLINE(R), Ovid EMBASE, CNKI, Wanfang, VIP databases, the Cochrane Library, and medRxiv for primary articles in English or Chinese up to March 30, 2020 to systematically evaluate the risk factors for severe patients in China. Mean difference or standardize mean difference and odds ratio with 95% confidence intervals were performed by random-effect or fixed models in cases of significant heterogeneity between studies. We used I 2 to evaluate the magnitude of heterogeneity. A total of 54 articles involving about 7000 patients were eligible for this meta-analysis. In total, 52 of 67 parameters between severe and non-severe cases were significantly different. Elderly male patients with comorbidities including hypertension, diabetes, chronic obstructive pulmonary disease (COPD) cardiovascular disease, cerebrovascular disease, chronic kidney disease, or cancer were more common in severe COVID-19 patients. Regarding the clinical manifestations on admission, fever, cough, expectoration, dyspnea, chest distress, fatigue, headache, chills, anorexia, or abdominal pain were more prevalent in severe COVID-19 patients. The results of the clinical examination showed that high C-reactive protein (CRP), high lactate dehydrogenase (LDH), high D-dimer, and decreased T lymphocytes cells subsets, decreased lymphocyte may help clinicians predict the progression of severe illness in patients with COVID-19. Our findings will be conducive for clinician to stratify the COVID-19 patients to reduce mortality under the relative shortage of medical resources. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Principal Component Analysis Applications in COVID-19 Genome Sequence Studies.

RNA genomes from coronavirus have a length as long as 32 kilobases, and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the outbreak of coronavirus disease 2019 (COVID-19) pandemic has long sequences which made the analysis difficult. Over 20,000 sequences have been submitted to GISAID, and the number is growing fast each day which increased the difficulties in data analysis; however, genome sequence analysis is critical in understanding the COVID-19 and preventing the spread of the disease. In this study, a principal component analysis (PCA) was applied to the aligned large size genome sequences and the numerical numbers were converted from the letters using a published method designed for protein sequence cluster analysis. The study initialized with a shortlist sequence testing, and the PCA score plot showed high tolerance with low-quality data, and the major virus sequences from humans were separated from the pangolin and bat samples. Our study also successfully built a model for a large number of sequences with more than 20,000 sequences which indicate the potential mutation directions for the COVID-19 which can be served as a pretreatment method for detailed studies such as decision tree-based methods. In summary, our study provided a fast tool to analyze the high-volume genome sequences such as the COVID-19 and successfully applied to more than 20,000 sequences which may provide mutation direction information for COVID-19 studies.

Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients (preprint)

Background: Gastrointestinal manifestations and gut dysbiosis are prevalent after SARS-CoV2 infection.With the continuously increasing number of infected cases, more attention should be paid to this particular population in post-infection recovery.cWe aimed to investigate the potential beneficial effect of FMT on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Results: Gastrointestinal and psychological disorder (45.5%) were observed in COVID-19 patients during post-infection recovery, improvement of which were observed after FMT. Most of the lab results including blood routine and blood biochemistry, within the normal range. The general distribution of 69 different types of lymphocytes differed between before and after FMT. FMT exert significant effect on B cells which was characterized as decreased naive B cell ( P =0.012) and increased memory B cells ( P = 0.001) and non-switched B cells ( P = 0.012).The microbial community richness indicated by OTUs number, observed species and Chao1 estimators was marginally increased after FMT, whereas the community diversity estimated by the Shannon and Simpson index showed no significant changes after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteriato (9.2%). FMT can partially restore the gutdysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteriato (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium , which were dominant genera in the human gut microbiota and were beneficial for human health, had significantly increased after FMT. Conclusions: Gastrointestinal and gut dysbiosis were observed in COVID-19 patients during post-infection recovery. FMT can improve the immune functionality, restore the gut microbiota, alleviate gastrointestinal disorders, and may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.

A Peptide-Based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

The need for fully bio-based facemasks to counter coronavirus outbreaks: A perspective.

The onset of coronavirus pandemic has sparked a shortage of facemasks in almost all nations. Without this personal protective equipment, healthcare providers, essential workers, and the general public are exposed to the risk of infection. In light of the aforementioned, it is critical to balance the supply and demand for masks. COVID-19 will also ensure that masks are always considered as an essential commodity in future pandemic preparedness. Moreover, billions of facemasks are produced from petrochemicals derived raw materials, which are non-degradable upon disposal after their single use, thus causing environmental pollution and damage. The sustainable way forward is to utilise raw materials that are side-stream products of local industries to develop facemasks having equal or better efficiency than the conventional ones. In this regard, wheat gluten biopolymer, which is a by-product or co-product of cereal industries, can be electrospun into nanofibre membranes and subsequently carbonised at over 700 °C to form a network structure, which can simultaneously act as the filter media and reinforcement for gluten-based masks. In parallel, the same gluten material can be processed into cohesive thin films using plasticiser and hot press. Additionally, lanosol, a naturally-occurring substance, imparts fire (V-0 rating in vertical burn test), and microbe resistance in gluten plastics. Thus, thin films of flexible gluten with very low amounts of lanosol (<10 wt%) can be bonded together with the carbonised mat and shaped by thermoforming to create the facemasks. The carbon mat acting as the filter can be attached to the masks through adapters that can also be made from injection moulded gluten. The creation of these masks could simultaneously be effective in reducing the transmittance of infectious diseases and pave the way for environmentally benign sustainable products.