Bioinformatics-based SARS-CoV-2 epitopes design and the impact of Spike protein mutants on epitope humoral immunities

Graphical Background Epitope selection is the key to peptide vaccines development. Bioinformatics tools can efficiently improve the screening of antigenic epitopes and help to choose the right ones. Objective To predict, synthesize and testify peptide epitopes at spike protein, assess the effect of mutations on epitope humoral immunity, thus provide clues for the design and development of epitope peptide vaccines against SARS-CoV-2. Methods Bioinformatics servers and immunological tools were used to identify the helper T lymphocyte, cytotoxic T lymphocyte, and linear B lymphocyte epitopes on the S protein of SARS-CoV-2. Physicochemical properties of candidate epitopes were analyzed using IEDB, VaxiJen, and AllerTOP online software. Three candidate epitopes were synthesized and their antigenic responses were evaluated by binding antibody detection. Results A total of 20 antigenic, non-toxic and non-allergenic candidate epitopes were identified from 1502 epitopes, including 6 helper T-cell epitopes, 13 cytotoxic T-cell epitopes, and 1 linear B cell epitope. After immunization with antigen containing candidate epitopes S206-221, S403-425, and S1157-1170 in rabbits, the binding titers of serum antibody to the corresponding peptide, S protein, receptor-binding domain protein were (415044, 2582, 209.3), (852819, 45238, 457767) and (357897, 10528, 13.79), respectively. The binding titers to Omicron S protein were 642, 12878 and 7750, respectively, showing that N211L, DEL212 and K417N mutations cause the reduction of the antibody binding activity. Conclusions Bioinformatic methods are effective in peptide epitopes design. Certain mutations of the Omicron would lead to the loss of antibody affinity to Omicron S protein.

Prevalence of Sarcopenia in Patients With COVID-19: A Systematic Review and Meta-Analysis

Background It has been speculated that patients with sarcopenia are aggravated by the current novel coronavirus disease 2019 (COVID-19) epidemic. However, there is substantial uncertainty regarding the prevalence of sarcopenia in patients with COVID-19. Objectives The purpose of the study was to systematically evaluate the prevalence of sarcopenia in patients with COVID-19, including stratification by gender, study location, study population, study design, and diagnostic criteria. Design This is the systematic literature review and meta-analysis. Methods An electronic search was performed in MEDLINE/PubMed, Embase, Cochrane Library, and Web of Science and Scopus to identify observational studies reporting a prevalence estimate for sarcopenia in patients with COVID-19. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a meta-analysis was performed. Risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale (NOS) for cohort studies and Joanna Briggs Institute (JBI) manual for cross-sectional studies, and Stata 14.0 was used to perform meta-analyses. Results A total of 4,639 studies were initially identified. After removing the duplicates and applying the selection criteria, we reviewed 151 full-text studies. A total of 21 studies, including 5,407 patients, were eligible for inclusion in this review finally. The prevalence of sarcopenia in patients with COVID-19 in individual studies varied from 0.8 to 90.2%. The pooled prevalence of sarcopenia in COVID-19 was 48.0% (95% confidence interval, CI: 30.8 to 65.1%, I2 = 99.68%, p = 0.000). We did not find any significant differences in the prevalence estimates between gender specificity (OR = 1.34;95% CI = 0.80–2.26;p = 0.001). By sex, the prevalence was 42.5% (95% CI: 31.7 to 53.4%) in men and 35.7% (95% CI: 24.2 to 47.2%) in women. The prevalence estimates significantly varied based on population settings and different diagnostic criteria of sarcopenia. ICU patients (69.7, 95% CI: 51.7 to 85.2%) were more likely to suffer from sarcopenia compared to other population settings. Conclusion To our knowledge, this is the first meta-analysis reporting on the prevalence of sarcopenia in patients with COVID-19. Sarcopenia is frequently observed in patients with COVID-19, with varying prevalence across population settings. This study would be useful for clinicians to prompt the increasing awareness of identifying sarcopenia and developing interventions at patients with COVID-19 with high risk of sarcopenia. Further prospective longitudinal studies to define the association of sarcopenia and its prognostic outcomes in COVID-19 survivors are urgently needed to propose the most appropriate treatment strategies during their admission and discharge. Systematic Review Registration [www.crd.york.ac.uk/prospero/], identifier [CRD42022300431].

Re-emergence of Severe Acute Diarrhea Syndrome Coronavirus (SADS-CoV) in Guangxi, China, 2021 (preprint)

Severe acute diarrhea syndrome coronavirus (SADS-CoV) has had a major impact on the swine industry in China, but has not been detected since 2019. Using real-time qPCR and metagenomic surveillance we identified SADS-CoV in a pig farm experiencing diarrheal disease. Genomic analysis supported the undetected circulation of SADS-CoV since 2019.

Application of 2019 Novel Coronavirus (2019-nCoV) specific antibody detection for suspected cases screening

Comparing the accuracy of antibody detection reagents which based on different principles by the diagnosis of suspected cases of new crown, propose an efficient screening plan for suspected cases, and further provide a scientific basis for establishing a clinical screening path for high-risk populations. For 76 suspected cases of COVID-19 that were transferred to designated hospitals for isolation and observation due to the initial IgM antibody test, nasopharyngeal swab nucleic acid tests, serum trace virus neutralizing antibodies and three commercially available antibody test reagents with different principles were tested, combined with lung CT and the examination and clinical symptoms or other information, comprehensively judge the diagnosis or exclusion of the new crown, and compare the three kinds of serological antibody detection reagents with the clinical judgment results to compare the detection rates of the three detection methods. Through comprehensive judgment, 3 suspected cases are confirmed cases, and 73 suspected cases are excluded cases. Compared with the clinical diagnosis/exclusion results, among the three serological antibody detection methods, the chemiluminescence total antibody kit detect positive for all the 9 serums collected from the 3 confirmed cases in different time points, the detection specificity is 97.26% for 73 excluded cases, it's significantly higher than that of the chemiluminescence method IgM/IgG and the colloidal gold method IgM/IgG Separate testing (the specificity is 73.97% on the first day of admission). The chemiluminescence method for the detection of total antibodies to the 2019-nCoV has high sensitivity and high specificity, and can be used for preliminary screening of antibody detection in suspected cases. For the screening of target populations, the 2019-nCoV nucleic acid test should be performed first. If the nucleic acid test is negative, the screening path with the detection of serum total antibodies as the main indicator should be adopted.

Assessment of Reductions in Emission-driven Air Pollution during the Beijing Olympic Games, Shanghai World Expo, Guangzhou Asian Games and Wuhan COVID-19 Lockdown

Quantifying and comparing the effectiveness of different emission control strategies can provide insights for policy design and air quality management. In our previous work, we developed a wind-pollution decomposition (WPD) method that provides a robust tool to quantify meteorology-driven and emission-driven impacts on changes in air quality. In this study, we applied this method to quantify emission-driven impacts on the observed air quality changes during the three largest international socioeconomic mega-events in China, namely, Shanghai World Expo in 2010, Beijing Olympic Games in 2008, and Guangzhou Asian Games in 2010. We also applied the method to the air quality variation during the lockdown period in Wuhan due to COVID-19 and compared the emission-driven impacts on air quality among these events. The results quantitatively show that the emission-driven factor generally played a much stronger role (> 86%);the meteorology-driven factor promoted pollution mitigation during Wuhan, Beijing and Guangzhou events but worsened the air quality during Shanghai event. The emission-driven pollution reduction was largest in the Wuhan COVID-19 lockdown (64% NO2, 54% PM2.5 reductions), followed by Beijing Olympics (42% PM2.5, 31% NO2 reductions), The Wuhan COVID-19 impact on air quality improvement is not as effective as expected especially for O3, which implies the difficulty of air quality attainment under normal, non-lockdown daysComparison of these events show that shutdown or emission control measures applied to industries and power plants were generally benefit for PM2.5, SO2 and NO2 reduction, while those applied to on-road traffic control are less-effective for reducing NO2 and not works for the mean O3 reduction. The results imply that advanced control measures for vehicle exhaust and control strategies considering the interaction between O3 and NOx/VOC/PM are necessary. In addition, the ongoing supervision of control strategies implementation is one of the key issues for future air quality management in China.

Detrimental impact of contagious disease cues on consumer preference for anthropomorphic products

Despite the extensive use of anthropomorphism strategy in marketing practices, little research attention has been given to the environmental factors that influence consumer preference for anthropomorphic products. This research examines when and why contagious disease cues can influence consumer preference for anthropomorphic products. The results from four empirical experiments consistently show that when exposed to contagious disease cues, consumers exhibit a lower preference for anthropomorphic products (Study 1), which is mediated by social withdrawal (Study 2). Furthermore, our findings demonstrate that this detrimental effect would be attenuated for products in digital (vs. physical) format (Study 3), or in regions with low (vs. high) local severity of the contagious disease (Study 4). These findings contribute to the literature on contagious diseases and anthropomorphism and offer important managerial implications. Supplementary Information The online version contains supplementary material available at 10.1007/s11002-022-09614-x.

A Flexible Cap-and-Trade Policy and Limited Demand Information Effects on a Sustainable Supply Chain

Carbon emission reduction is increasingly becoming a public consensus, with governments formulating carbon emission policies, enterprises investing in emission abatement equipment, and consumers having a low-carbon preference. On the other hand, it is difficult for industry managers to obtain all the demand information. Based on this, this paper aims to investigate operations and coordination for a sustainable system with a flexible cap-and-trade policy and limited demand information. Newsvendor and distribution-free newsvendor models are formulated to show the validity of limited information. Stackelberg game is exploited to derive optimal abatement and order quantity solutions under centralized and decentralized systems. The revenue-sharing and two-part tariff contracts are then proposed to coordinate the decentralized system with limited demand information. Numerical analyses complement the theoretical results. We list some major findings. Firstly, we discover that using abatement equipment can effectively reduce emissions and increase profits. Secondly, the distribution-free approach is effective and acceptable for a system where only mean and variance information is informed. Thirdly, the mean parameter has a greater impact on profits and emissions comparing with the other seven parameters. Finally, we show that both contracts may achieve perfect coordination, and the two-part tariff contract is more robust.

A vimentin-targeting oral compound with host-directed antiviral and anti-inflammatory actions addresses multiple features of COVID-19 and related diseases (preprint)

Damage in COVID-19 results from both the SARS-CoV-2 virus and its triggered overreactive host immune responses. Therapeutic agents that focus solely on reducing viral load or hyperinflammation fail to provide satisfying outcomes in all cases. Although viral and cellular factors have been extensively profiled to identify potential anti-COVID targets, new drugs with significant efficacy remain to be developed. Here, we report the potent preclinical efficacy of ALD-R491, a vimentin-targeting small molecule compound, in treating COVID-19 through its host-directed antiviral and anti-inflammatory actions. We found that by altering the physical properties of vimentin filaments, ALD-491 affected general cellular processes as well as specific cellular functions relevant to SARS-CoV-2 infection. Specifically, ALD-R491 reduced endocytosis, endosomal trafficking, and exosomal release, thus impeding the entry and egress of the virus; increased the microcidal capacity of macrophages, thus facilitating the pathogen clearance; and enhanced the activity of regulatory T cells, therefore suppressing the overreactive immune responses. In cultured cells, ALD-R491 potently inhibited the SARS-CoV-2 spike protein and human ACE2-mediated pseudoviral infection. In aged mice with ongoing, productive SARS-CoV-2 infection, ALD-R491 reduced disease symptoms as well as lung damage. In rats, ALD-R491 also reduced bleomycin-induced lung injury and fibrosis. Our results indicate a unique mechanism and significant therapeutic potential for ALD-R491 against COVID-19. We anticipate that ALD-R491, an oral, fast-acting, and non-toxic agent targeting the cellular protein with multipart actions, will be convenient, safe, and broadly effective, regardless of viral mutations, for patients with early- or late-stage disease, post-COVID complications and other related diseases. IMPORTANCEWith the Delta variant currently fueling a resurgence of new infections in the fully-vaccinated population, developing an effective therapeutic drug is especially critical and urgent in fighting COVID-19. In contrast to the many efforts to repurpose existing drugs or address only one aspect of COVID-19, we are developing a novel agent with first-in-class mechanism-of-actions that address both the viral infection and the overactive immune system in the pathogenesis of the disease. Unlike virus-directed therapeutics that may lose efficacy due to viral mutations and immunosuppressants that require ideal timing to be effective, this agent, with its unique host-directed antiviral and anti-inflammatory actions, can work against all variants of the virus, be effective during all stages of the disease, and even resolve post-disease damage and complications. A further development of the compound will provide an important tool in the fight against COVID-19, its complications, as well as future outbreaks of new viruses.

Pre-existing antibodies targeting a linear epitope on SARS-CoV-2 S2 cross-reacted with commensal gut bacteria and shaped vaccine induced immunity (preprint)

The origins of pre-existing SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the pre-existing S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by pre-existing antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we proved that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 specific monoclonal antibodies were isolated from naïve SPF mice and proved to cross-react with commensal gut bacteria collected from both human and mouse. Mice with high levels of pre-existing S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of pre-existing S2 and P144 reactive antibodies correlated positively with RBD specific binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Finally, we provided data demonstrating that immunization of a SARS-CoV-2 S DNA vaccine could alter the gut microbiota compositions of mice.

Modeling team efficiency for international production assignments in Chinese manufacturing multinationals

In 2019 China accounted for 14 percent of world total outward foreign direct investment, with 188 countries recipients of this investment. However research suggests that 67 percent of this investment is considered unsuccessful. Furthermore, the current Covid-19 outbreak has severely hindered global economic and trade activities. This is partly due to an under-efficiency of Chinese expatriate executives resulting from the lack of cultural intelligence of these executives to maximize team efficiency in production. From a data set of 358 expatriate Chinese executives, this research utilizes structural equation modeling to examine the role of expatriate executives' cultural intelligence on team efficiency. The research shows that the relationship between an expatriate executive’s cultural intelligence and team efficiency is mediated by their ability to recognize international opportunity and moderated by openness to experience. Additional leadership development on cultural intelligence of expatriate executives will improve international efficiency and wider multinational efficiency.

The clinical observation of Winona anti-sensitive moisturizing tolerance-extreme cream in the prevention and control of COVID-19 for medical staff wearing medical masks to repair the skin barrier

Objective: Observe the effect of using WINONA Anti-Sensitive Moisturizing Tolerance-Extreme Cream on the repairation of skin barrier function and improvement of sensitive skin after medical staff wearing medical masks.

Impact of the COVID-19 Pandemic on Willingness to Adopt Healthy Dietary Habits in China (preprint)

Background: To investigate impact of the 2019 novel coronavirus disease (COVID-19) pandemic on willingness to adopt healthy dietary habits in China.  Methods: A survey was carried out, and subjective perception of impact due to COVID-19 and willingness to change dietary habits were obtained. Results: A total of 22,459 subjects were derived from China, with an average age of 27.9±7.8 years old. Of them, the mean score of willingness to adopt healthy dietary habits was 2.2 (ranges from -9 to 9). Multivariate regression analysis showed that the impact of the COVID-19 pandemic (epidemic concern, impact of psychology, impact of work or study) are associated with a higher score of willingness to adopt healthy dietary habits among female, the older, on-medical worker, and individuals married or with higher education level, normal BMI. Conclusions: There was a positive improvement to a proper diet, so the changing features of diets should be considered in nutritional interventions for maintaining health, and prevention and control COVID-19 during the pandemic period.

The study of relationship between acute myocardial injury and coagulation function in patients with COVID-19 / 医学研究生学报

ObjectiveTo study the relationship between acute myocardial injury（AMI） and coagulation function in patients with COVID-19.MethodsA retrospective study was carried out to record the general and laboratory data of 133 patients diagnosed with COVID-19 who were hospitalized in Wuhan TongJi Guanggu Hospital, Wuhan, Hubei Province from February 10 to February 29, 2020. The laboratory data includes blood routine, liver and renal function, myocardial infarction tests, coagulation function, inflammatory factors, hypersensitive C-reactive protein, procalcitonin etc. The patients were divided into two groups according to cardiac troponin I（TNI）34.2 ug/L. The differences of general conditions and laboratory data between the two groups were compared. Besides, the correlation between coagulation function and coagulation function, and the ROC curve of D-dimer in AMI were conducted .ResultsAmong the 133 patients, 9 (6.77%) had cTnI greater than 34.2 μg/L, and 124 (93.23%) had normal cTnI. There were significant differences between the two groups in age, COPD history, blood routine (neutrophil count, lymphocyte count, platelet count), myoglobin, liver function (direct bilirubin, indirect bilirubin), cytokines (IL-2 receptor, IL-6, IL-8, IL-10, TNF-α), coagulation function (PT, PTA, D-dimer). D-dimer level was positively correlated with TnI, CK-MB and myoglobin levels. The cut off value of D-dimer was 2.35 μg/ml in acute myocardial injury.ConclusionAcute myocardial injury in COVID-19 patients may be related to coagulation dysfunction. Therefore, monitoring of coagulation function dynamically, screening of thrombus and starting anticoagulant and antiplatelet therapy timely help to reduce acute myocardial injury.

Impact of the COVID-19 pandemic on willingness to adopt healthy dietary habits in China (preprint)

Background: To investigate impact of the 2019 novel coronavirus disease (COVID-19) pandemic on willingness to adopt healthy dietary habits in China.Methods: A survey was carried out, and subjective perception of impact due to COVID-19 and willingness to change dietary habits were obtained.Results: A total of 22,459 subjects were derived from China, with an average age of 27.9±7.8 years old. Of them, the mean score of willingness to adopt healthy dietary habits was 2.2 (ranges from -9 to 9). Multivariate regression analysis showed that the impact of the COVID-19 pandemic (epidemic concern, impact of psychology, impact of work or study) are associated with a higher score of willingness to adopt healthy dietary habits among female, the older, on-medical worker, and individuals married or with higher education level, normal BMI.Conclusions: There was a positive improvement to a proper diet, so the changing features of diets should be considered in nutritional interventions for maintaining health, and prevention and control COVID-19 during the pandemic period.

Estimating the Number of Infected Cases in COVID-19 Pandemic (preprint)

The COVID-19 pandemic has caused major disturbance to human life. An important reason behind the widespread social anxiety is the huge uncertainty about the pandemic. One major uncertainty is how many or what percentage of people have been infected? There are published and frequently updated data on various statistics of the pandemic, at local, country or global level. However, due to various reasons, many cases were not included in those reported numbers. We propose a structured approach for the estimation of the number of unreported cases, where we distinguish cases that arrive late in the reported numbers and those who had mild or no symptoms and thus were not captured by any medical system at all. We use post-report data for the estimation of the former and population matching to the latter. We estimate that the reported number of infected cases in the US should be corrected by multiplying a factor of 220.54% as of Apr 20, 2020. The infection ratio out of the US population is estimated to be 0.53%, implying a case mortality rate at 2.85% which is close to the 3.4% suggested by the WHO.

Clinical characteristics of survivors and non-survivors, medical and non-medical staff members with 2019-nCoV pneumonia in Wuhan, China: a descriptive study (preprint)

Objectives: In December 2019，the 2019 novel coronavirus ( 2019-nCoV ) emerged in Wuhan, China, leading to a cluster of severe pneumonia cases. Medical staff members on the front line were also infected. We compared the epidemiology, clinical characteristics, and treatment measures of survivors and non-survivors and the different clinical outcomes of medical staff members and non-medical members of the community infected with 2019-nCoV. Methods: We included 81 patients with adult 2019-nCoV in Hankou Hospital from mid-January to mid-February 2020 in this single-center retrospective study. Data were compared between survivors and non-survivors and between medical staff members and non-medical individuals. Results: All 38 medical staff members were infected by patients while working. Only 2 (2.5%) non-medical individuals had a clear history of exposure to 2019-nCoV patients. The median age was 49 years (interquartile range [IQR], 35-59; range, 23-89 years), and 42 (51.9%) were women. We found that the median age,comorbidity, and some laboratory outcomes(lymphocyte count, urea nitrogen, aspartate aminotransferase, lactate dehydrogenase, etc.)differed significantly between survivors and non-survivors. There were also significant differences in the time from onset to admission, disease classification, comorbidity, and prognosis between medical staff members and non-medical individuals. All medical staff members were cured, while 13 (30.2%) non-medical individuals died. Conclusions: Older males with comorbidities are more likely to be affected by 2019-nCoV. Significant changes in some laboratory markers may indicate a poor prognosis. Medical staff members may have had better prognoses due to fewer comorbidities and better medical compliance. Key words: 2019-nCoV; Clinical characteristics; Mortality; comorbidity; Survivors; Non-survivors; Medical Staff

Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China (preprint)

Background Although the outbreak of Coronavirus disease 2019 (COVID-19) has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. Methods For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020. This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation. Results We included 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Lymphopenia occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83-225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had acute respiratory distress syndrome (ARDS). The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. Interpretation Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment.