Precise modification of the surface charge of antigen enhances vaccine immunogenicity.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

Safety and immunogenicity of inactivated COVID-19 vaccine CoronaVac and the RBD-dimer-based COVID-19 vaccine ZF2001 in chronic hepatitis B patients.

Background and aims: Although COVID-19 vaccination is recommended for the patients with chronic liver disease, the clinical outcomes of COVID-19 vaccinated in patients with chronic hepatitis B (CHB) has not been well characterized. The study aimed to explore the safety and specific antibody responses following COVID-19 vaccination among CHB patients. Methods: Patients with CHB were included. All patients were vaccinated with two doses of inactivated vaccine (CoronaVac) or three doses of adjuvanted protein subunit vaccine (ZF2001). The adverse events were recorded and neutralizing antibody (NAb) were determined 14 days following the whole-course vaccination. Results: A total of 200 patients with CHB were included. Specific NAb against SARS-CoV-2 were positive in 170 (84.6%) patients. The median (IQR) concentrations of NAb were 16.32 (8.44-34.10) AU/ml. Comparison of immune responses between CoronaVac and ZF2001 vaccines showed no significant differences in neither the concentrations of NAb nor the seropositive rates (84.4 vs. 85.7%). Moreover, we observed lower immunogenicity in older patients and in patients with cirrhosis or underlying comorbidities. The incidences of adverse events were 37 (18.5%) with the most common adverse event as injection side pain [25 (12.5%)], followed by fatigue [15 (7.5%)]. There were no differences in the frequencies of adverse between CoronaVac and ZF2001 (19.3% vs. 17.6%). Almost all of the adverse reactions were mild and self-resolved within a few days after vaccination. Severe adverse events were not observed. Conclusions: COVID-19 vaccines, CoronaVac and ZF2001 had a favorable safety profile and induced efficient immune response in patients with CHB.

A novel mRNA vaccine, SYS6006, against SARS-CoV-2.

The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. In vitro ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4+Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2.

The normalization of COVID-19 epidemic prevention and control calls for patriotic health campaign inherit and innovation

In order to summarize the experience of COVID-19 prevention and control, review the glorious course of the 70th anniversary of China's patriotic health campaign, and realize the Healthy China. This paper summarizes the great achievements of China's patriotic health campaign in the past 70 years, and reviews the trend of sustainable vector management, especially the progress of China and Zhejiang Province in the construction of patriotic health campaign organization, vector monitoring, early warning, informatization, prevention and control and research work in the last 10 years. The results found that the patriotic health campaign has significantly improved the health level of the Chinese people. Zhejiang Province has demonstrated and led the comprehensive monitoring of vector and vector infectious diseases, and exploration of sustainable vectors management in rural area, first to carry out the "construction of eliminate four vector villages focusing on mosquito-free and fly-free", and promoted the patriotic health campaign at a high level. The paper considers that the patriotic health campaign is a successful practice of our Party's mass line to health prevention. The experience of COVID-19 prevention and control shows that, Prevention and control the communicable disease needs the concept of patriotic health campaign and the support of public health, all for the people's health, The Times call for a patriotic health campaign with Inheritance of history, rich connotation and innovative methods. We must re-understand the extreme importance of communicable disease prevention and control, pay more attention to the potential harm of vectors in the cross-species transmission of communicable diseases, give full play to the unique role of patriotic health campaign in disease prevention and control and safeguarding people's health, and accelerate the Healthy China action.

Who and which regions are at high risk of returning to poverty during the COVID-19 pandemic?

Pandemics such as COVID-19 and their induced lockdowns/travel restrictions have a significant impact on people’s lives, especially for lower-income groups who lack savings and rely heavily on mobility to fulfill their daily needs. Taking the COVID-19 pandemic as an example, this study analysed the risk of returning to poverty for low-income households in Hubei Province in China as a result of the COVID-19 lockdown. Employing a dataset including information on 78,931 government-identified poor households, three scenarios were analysed in an attempt to identify who is at high risk of returning to poverty, where they are located, and how the various risk factors influence their potential return to poverty. The results showed that the percentage of households at high risk of returning to poverty (falling below the poverty line) increased from 5.6% to 22% due to a 3-month lockdown. This vulnerable group tended to have a single source of income, shorter working hours, and more family members. Towns at high risk (more than 2% of households returning to poverty) doubled (from 27.3% to 46.9%) and were mainly located near railway stations;an average decrease of 10–50 km in the distance to the nearest railway station increased the risk from 1.8% to 9%. These findings, which were supported by the representativeness of the sample and a variety of robustness tests, provide new information for policymakers tasked with protecting vulnerable groups at high risk of returning to poverty and alleviating the significant socio-economic consequences of future pandemics.

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients.

Background. Interferon is a marker of host antiviral immunity, which is disordered in COVID-19 patients. ERV can affect the secretion of interferon through the cGAS-STING pathway. In this study, we explored whether IFN-I and HERV-K (HML-2) were activated in COVID-19 patients and whether there was an interaction between them. Methods. We collected blood samples from COVID-19 patients and healthy controls. We first detected the expression of HERV-K (HML-2) gag, env, and pol genes and IFN-I-related genes between patients and healthy people by qPCR, synchronously detected VERO cells infected with SARS-CoV-2. Then, the chromosome distributions of highly expressed HERV-K (HML-2) gag, env, and pol genes were mapped by the next-generation sequencing results, and GO analysis was performed on the related genes. Results. We found that the HERV-K (HML-2) gag, env, and pol genes were highly expressed in COVID-19 patients and VERO cells infected with SARS-CoV-2. The interferon-related genes IFNB1, ISG15, and IFIT1 were also activated in COVID-19 patients, and GO analysis showed that HERV-K (HML-2) can regulate the secretion of interferon. Conclusions. The high expression of HERV-K (HML-2) might activate the increase of interferon in COVID-19 patients, proving that HERV-K does not only play a negative role in the human body.

Accelerated biological aging in COVID-19 patients.

Chronological age is a risk factor for SARS-CoV-2 infection and severe COVID-19. Previous findings indicate that epigenetic age could be altered in viral infection. However, the epigenetic aging in COVID-19 has not been well studied. In this study, DNA methylation of the blood samples from 232 healthy individuals and 413 COVID-19 patients is profiled using EPIC methylation array. Epigenetic ages of each individual are determined by applying epigenetic clocks and telomere length estimator to the methylation profile of the individual. Epigenetic age acceleration is calculated and compared between groups. We observe strong correlations between the epigenetic clocks and individual's chronological age (r > 0.8, p < 0.0001). We also find the increasing acceleration of epigenetic aging and telomere attrition in the sequential blood samples from healthy individuals and infected patients developing non-severe and severe COVID-19. In addition, the longitudinal DNA methylation profiling analysis find that the accumulation of epigenetic aging from COVID-19 syndrome could be partly reversed at late clinic phases in some patients. In conclusion, accelerated epigenetic aging is associated with the risk of SARS-CoV-2 infection and developing severe COVID-19. In addition, the accumulation of epigenetic aging from COVID-19 may contribute to the post-COVID-19 syndrome among survivors.

Practice and experience of regional medical center entrance linkage and closed-loop management under the wartime situation of the COVID-19 in China

On 28 July 2021, the first indigenous case of novel coronavirus pneumonia (COVID-19) emerged in Yangzhou, marking the beginning of a public health crisis caused by the new coronavirus pneumonia. It is a significant challenge for hospitals to carry out prevention and control measures to ensure the safety of medical professionals and patients when facing the changes in an epidemic situation. Subei People’s Hospital, as one of the first group of “Grade III-class A” hospitals in Jiangsu Province and the Yangzhou Regional Medical Centre, responded quickly and scientifically to prevent and control the disease. A closed-loop management system was implemented at the hospital entrance (consisting of the outpatient clinic, emergency clinic, fever clinic, and buffer ward) and an epidemic prevention and control group was established with the assistance of multiple departments. This group optimized the pre-screening and triage system, standardized the fever clinic consultation process, and improved the construction of an information-based prevention and control network so that patients were detected, diagnosed, isolated, and treated early. The emergency management capability was improved to achieve zero missed consultations of patients attending for COVID-19 and to effectively maintain medical order during this critical period. This current report systematically summarizes the operational practices and the effectiveness achieved by implementation of the entrance closed-loop management in the hospital and analyzed the key operational issues for future reference by medical institutions and management departments.

Thermodynamic assessment of a cogeneration system with CSP Driven-Brayton and Rankine cycles for electric power and hydrogen production in the framework of the energy and water nexus

In increasingly energy-dependent world, there is a question mark over the viability of fossil fuel resources. To tackle this issue, an integrated poly-generation system based on concentrated solar power is proposed to feed in the city grid and produce hydrogen as a clean energy carrier. Concerning the COVID-19 outbreak, all countries are in dire need of oxygen. Therefore, the produced oxygen in this system can be considered as an added value. The introduced scheme applies solar energy to supply thermal energy to a Brayton cycle. Two bottoming Rankine cycles are employed to empower a PEM electrolyzer using the residual heat from the gas turbine. The system is modelled using the Engineering Equations Solver for a comprehensive thermo-economic analysis. The exergy destruction analysis proved a significant loss of exergy by the solar field, illustrating the necessity to address this in future research. Afterwards, six design variables were selected and then optimized for the proposed system using the NSGA-II. Based on the TOPSIS approach, exergy efficiency, and capital cost rate, the objective functions were 22.2% and 272.6 $/h, respectively. Finally, a case study was performed to investigate the impact of solar irradiation and ambient temperature on system outputs.

Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients.

Objectives: Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients. Methods: COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests. Results: A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody. Conclusions: Our findings show the severe COVID-19 patients' antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.

Impact of COVID-19 Pandemic on Pre-Treatment Delays, Detection, and Clinical Characteristics of Tuberculosis Patients in Ningxia Hui Autonomous Region, China.

Background: To contain the pandemic of COVID-19, China has implemented a series of public health interventions that impacted the tuberculosis control substantially, but these impacts may vary greatly depending on the severity of the local COVID-19 epidemic. The impact of COVID-19 on TB control in Ningxia Hui Autonomous Region is little known. Methods: Based on the national TB Information Management System (TBIMS), this study accessed the actual impact of COVID-19 on TB by comparing TB notifications, pre-treatment delays, and clinical characteristics of TB cases between 2020 COVID-19 period and 2017-2019 baseline. The data were divided into three periods based on the response started to fight against COVID-19 in Ningxia Hui Autonomous Region, including the control period (10 weeks before the pandemic), intensive period (10 weeks during the Ningxia Hui Autonomous Region lockdown), and regular (10 additional weeks after Ningxia Hui Autonomous Region reopen). Results: TB notification dropped sharply in the first week of the intensive period but took significantly longer to return to the previous level in 2020 compared with the 2017-2019 baseline. Totally, the TB notification rates decreased by more than 60% in the intensive period of COVID-19 compared with the average level of 2017-2019. The sputum smear-positive rate of TB patients diagnosed in intensive period of COVID-19 was significantly higher than that in the corresponding periods of 2017-2019 (P < 0.001). The rate of cavity on X-ray inspection of TB cases diagnosed in the intensive period of COVID-19 was significantly higher than that in period 2 of 2017-2019 (23.5 vs. 15.4%, P = 0.004). The patients' delay in the intensive period was significantly longer than that before the pandemic (P = 0.047). Conclusions: The TB notification in Ningxia was impacted dramatically by the pandemic of COVID-19. To compensate for the large numbers of missed diagnosis as well as delayed diagnosis during the intensive period of COVID-19, an urgent restoration of normal TB services, and further emphasis on enhanced active case finding and scale-up of household contact tracing and screening for TB-related symptoms or manifestation, will be essential.

Machine Learning-Based Decision Model to Distinguish Between COVID-19 and Influenza: A Retrospective, Two-Centered, Diagnostic Study.

BACKGROUND: Considering the current situation of the novel coronavirus disease (COVID-19) epidemic control, it is highly likely that COVID-19 and influenza may coincide during the approaching winter season. However, there is no available tool that can rapidly and precisely distinguish between these two diseases in the absence of laboratory evidence of specific pathogens. METHODS: Laboratory-confirmed COVID-19 and influenza patients between December 1, 2019 and February 29, 2020, from Zhongnan Hospital of Wuhan University (ZHWU) and Wuhan No.1 Hospital (WNH) located in Wuhan, China, were included for analysis. A machine learning-based decision model was developed using the XGBoost algorithms. RESULTS: Data of 357 COVID-19 and 1893 influenza patients from ZHWU were split into a training and a testing set in the ratio 7:3, while the dataset from WNH (308 COVID-19 and 312 influenza patients) was preserved for an external test. Model-based decision tree selected age, serum high-sensitivity C-reactive protein and circulating monocytes as meaningful indicators for classifying COVID-19 and influenza cases. In the training, testing and external sets, the model achieved good performance in identifying COVID-19 from influenza cases with a corresponding area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI 0.93, 0.96), 0.93 (95% CI 0.90, 0.96), and 0.84 (95% CI: 0.81, 0.87), respectively. CONCLUSION: Machine learning provides a tool that can rapidly and accurately distinguish between COVID-19 and influenza cases. This finding would be particularly useful in regions with massive co-occurrences of COVID-19 and influenza cases while limited resources for laboratory testing of specific pathogens.

Clinical evidence of an interferon-glucocorticoid therapeutic synergy in COVID-19.

Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.

Cell-mediated immunity to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses spread unscrupulously virtually every corner on the planet in a very quick speed leading to an unprecedented world pandemic of COVID-19 claiming a great many of people's life. Paramount importance has been given to the studies on the virus itself including genomic variation and viron structure, as well as cell entry pathway and tissue residence. Other than that, to learn the main characteristic of host immunity responding to SARS-CoV-2 infection is an eminent task for restraining virus and controlling disease progress. Beside antibody production in response to SARS-CoV-2 infection, host cellular immunity plays an indispensable role in impeding virus replication and expansion at various stages of COVID-19 disease. In this review, we summarized the recent knowledge regarding the aberrant regulation and dysfunction of multiple immune cells during SARS-CoV-2 infection. This includes the dysregulation of immune cell number, Th polarity, cytokine storm they implicated with, as well as cell function exhaustion after chronic virus stimulation. Notwithstanding that many obstacles remain to be overcome, studies on immunotherapy for COVID-19 treatment based on the known features of host immunity in response to SARS-CoV-2 infection offer us tangible benefits and hope for making this SARS-CoV-2 pandemic under control.

HDL-scavenger receptor B type 1 facilitates SARS-CoV-2 entry.

Responsible for the ongoing coronavirus disease 19 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through binding of the viral spike protein (SARS-2-S) to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). Here we show that the high-density lipoprotein (HDL) scavenger receptor B type 1 (SR-B1) facilitates ACE2-dependent entry of SARS-CoV-2. We find that the S1 subunit of SARS-2-S binds to cholesterol and possibly to HDL components to enhance viral uptake in vitro. SR-B1 expression facilitates SARS-CoV-2 entry into ACE2-expressing cells by augmenting virus attachment. Blockade of the cholesterol-binding site on SARS-2-S1 with a monoclonal antibody, or treatment of cultured cells with pharmacological SR-B1 antagonists, inhibits HDL-enhanced SARS-CoV-2 infection. We further show that SR-B1 is coexpressed with ACE2 in human pulmonary tissue and in several extrapulmonary tissues. Our findings reveal that SR-B1 acts as a host factor that promotes SARS-CoV-2 entry and may help explain viral tropism, identify a possible molecular connection between COVID-19 and lipoprotein metabolism, and highlight SR-B1 as a potential therapeutic target to interfere with SARS-CoV-2 infection.

Association of Daily Wear of Eyeglasses With Susceptibility to Coronavirus Disease 2019 Infection.

Importance: The proportion of daily wearers of eyeglasses among patients with coronavirus disease 2019 (COVID-19) is small, and the association between daily wear of eyeglasses and COVID-19 susceptibility has not been reported. Objective: To study the association between the daily wearing of eyeglasses and the susceptibility to COVID-19. Design, Setting, and Participants: This cohort study enrolled all inpatients with COVID-19 in Suizhou Zengdu Hospital, Suizhou, China, a designated hospital for COVID-19 treatment in the area, from January 27 to March 13, 2020. COVID-19 was diagnosed according to the fifth edition of Chinese COVID-19 diagnostic guidelines. The proportion of persons with myopia who wore eyeglasses in Hubei province was based on data from a previous study. Exposures: Daily wearing of eyeglasses for more than 8 hours. Main Outcomes and Measures: The main outcomes were the proportions of daily wearers of eyeglasses among patients admitted to the hospital with COVID-19 and among the local population. Data on exposure history, clinical symptoms, underlying diseases, duration of wearing glasses, and myopia status and the proportion of people with myopia who wore eyeglasses in Hubei province were collected. People who wore glasses for more than 8 hours a day were defined as long-term wearers. Results: A total of 276 patients with COVID-19 were enrolled. Of these, 155 (56.2%) were male, and the median age was 51 (interquartile range, 41-58) years. All those who wore glasses for more than 8 hours a day had myopia and included 16 of 276 patients (5.8%; 95% CI, 3.04%-8.55%). The proportion of people with myopia in Hubei province, based on a previous study, was 31.5%, which was much higher than the proportion of patients with COVID-19 who had myopia in this sample. Conclusions and Relevance: In this cohort study of patients hospitalized with COVID-19 in Suizhou, China, the proportion of inpatients with COVID-19 who wore glasses for extended daily periods (>8 h/d) was smaller than that in the general population, suggesting that daily wearers of eyeglasses may be less susceptible to COVID-19.

Retrospective Multicenter Cohort Study Shows Early Interferon Therapy Is Associated with Favorable Clinical Responses in COVID-19 Patients.

Interferons (IFNs) are widely used in treating coronavirus disease 2019 (COVID-19) patients. However, a recent report of ACE2, the host factor mediating SARS-Cov-2 infection, identifying it as interferon-stimulated raised considerable safety concern. To examine the association between the use and timing of IFN-α2b and clinical outcomes, we analyzed in a retrospective multicenter cohort study of 446 COVID-19 patients in Hubei, China. Regression models estimated that early administration (≤5 days after admission) of IFN-α2b was associated with reduced in-hospital mortality in comparison with no admission of IFN-α2b, whereas late administration of IFN-α2b was associated with increased mortality. Among survivors, early IFN-α2b was not associated with hospital discharge or computed tomography (CT) scan improvement, whereas late IFN-α2b was associated with delayed recovery. Additionally, early IFN-α2b and umifenovir alone or together were associated with reduced mortality and accelerated recovery in comparison with treatment with lopinavir/ritonavir (LPV/r) alone. We concluded that administration of IFN-α2b during the early stage of COVID-19 could induce favorable clinical responses.