Microneedles: An Emerging Vaccine Delivery Tool and a Prospective Solution to the Challenges of SARS-CoV-2 Mass Vaccination.

Vaccination is an effective measure to prevent infectious diseases. Protective immunity is induced when the immune system is exposed to a vaccine formulation with appropriate immunogenicity. However, traditional injection vaccination is always accompanied by fear and severe pain. As an emerging vaccine delivery tool, microneedles overcome the problems associated with routine needle vaccination, which can effectively deliver vaccines rich in antigen-presenting cells (APCs) to the epidermis and dermis painlessly, inducing a strong immune response. In addition, microneedles have the advantages of avoiding cold chain storage and have the flexibility of self-operation, which can solve the logistics and delivery obstacles of vaccines, covering the vaccination of the special population more easily and conveniently. Examples include people in rural areas with restricted vaccine storage facilities and medical professionals, elderly and disabled people with limited mobility, infants and young children afraid of pain. Currently, in the late stage of fighting against COVID-19, the main task is to increase the coverage of vaccines, especially for special populations. To address this challenge, microneedle-based vaccines have great potential to increase global vaccination rates and save many lives. This review describes the current progress of microneedles as a vaccine delivery system and its prospects in achieving mass vaccination against SARS-CoV-2.

Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.

The coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2 infection has become a global pandemic due to the high viral transmissibility and pathogenesis, bringing enormous burden to our society. Most patients infected by SARS-CoV-2 are asymptomatic or have mild symptoms. Although only a small proportion of patients progressed to severe COVID-19 with symptoms including acute respiratory distress syndrome (ARDS), disseminated coagulopathy, and cardiovascular disorders, severe COVID-19 is accompanied by high mortality rates with near 7 million deaths. Nowadays, effective therapeutic patterns for severe COVID-19 are still lacking. It has been extensively reported that host metabolism plays essential roles in various physiological processes during virus infection. Many viruses manipulate host metabolism to avoid immunity, facilitate their own replication, or to initiate pathological response. Targeting the interaction between SARS-CoV-2 and host metabolism holds promise for developing therapeutic strategies. In this review, we summarize and discuss recent studies dedicated to uncovering the role of host metabolism during the life cycle of SARS-CoV-2 in aspects of entry, replication, assembly, and pathogenesis with an emphasis on glucose metabolism and lipid metabolism. Microbiota and long COVID-19 are also discussed. Ultimately, we recapitulate metabolism-modulating drugs repurposed for COVID-19 including statins, ASM inhibitors, NSAIDs, Montelukast, omega-3 fatty acids, 2-DG, and metformin.

Dynamic variation and inhalation exposure of organophosphates esters and phthalic acid esters in face masks.

The coronavirus pandemic (COVID-19) has posed a huge global health threat since December 2019. Wearing face masks is known as an effective measure for controlling the wide spread of COVID-19 and its variants. But on the other hand, face masks could be a potential source of organophosphate esters (OPEs) and phthalic acid esters (PAEs) as they are extensively added in masks. However, knowledge associated with the occurrence as well as inhalation risks of OPEs and PAEs in masks is limited. In this study, OPEs and PAEs were determined in different types of mask samples collected from the local market. OPEs and PAEs were detected in mask samples ranging from 36.7 to 855 ng/g, and from 251 to 3830 ng/g, respectively. Relatively lower OPEs and PAEs concentrations were observed in disposable mask for toddlers. Simulated inhalation experiment indicated that the mass loss of OPEs and PAEs was 136 and 3910 ng/mask in disposable masks, 71.9 and 763 ng/mask in disposable mask for toddlers, 924 and 1020 ng/mask in N95 mask after 12 h, respectively. Significantly negative correlations were exhibited between the decrement of OPEs in masks and the increment of OPEs in corresponding polyurethane foams (PUFs) during the course, elucidating OPEs released from masks could be well captured by PUFs. With regard to the variation over time, predominant OPE and PAE analogues showed semblable release and absorption tendency in mask and corresponding PUF. Inhalation exposure risk of OPEs and PAEs was estimated based on the increment of pollutants in PUF. The estimated daily intakes (EDIs), hazard index (HI) and carcinogenic risk (CR) were also calculated and they were within the threshold levels. This study provides the evidence of OPEs and PAEs releasing from the face masks during wearing and unveiled a potential source of OPEs and PAEs exposure to humans.

Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2.

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

Outbreak control management: Lessons from SARS-CoV-2 infections in 2020-2022 in Hong Kong, an international municipality with high-frequency travelers.

The control management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is one of the most challenges in the 21st century. By May 8th, 2022, SARS-CoV-2 has infected over 510 million people with 6.2 million death worldwide and over 1.2 million people with 9133 deaths in the fifth wave of infection in Hong Kong. The government responded rapidly in the early days of the 2020 outbreak, and the results were encouraging to control COVID-19 outbreak unavailable of vaccine. The quick responses to the epidemic alerts, for example, public education and control policies, kept residents safe from infection in the city with such a high population density and large-scale travelers. Nevertheless, the extremely high infectivity, Omicron variant infections, and the shortcomings of transmission control measures led to uncontrollable outbreak in 2022. The weak immunity groups, elderly and children, experienced a high hospitalization rate and mortality rate because of low vaccination rate. Currently, the infection is under well controlled. This study timely summarizes the challenges, policy, and lessons of SARS-CoV-2 outbreak control from 2020 to 2022. More importantly, the lesson and policy revealed from this study may be beneficial and applied to other cities with the outbreak of highly infectious SARS-CoV-2.

The effects of SARS-CoV-2 infection on modulating innate immunity and strategies of combating inflammatory response for COVID-19 therapy.

The global pandemic of COVID-19 has caused huge causality and unquantifiable loss of social wealth. The innate immune response is the first line of defense against SARS-CoV-2 infection. However, strong inflammatory response associated with dysregulation of innate immunity causes severe acute respiratory syndrome (SARS) and death. In this review, we update the current knowledge on how SARS-CoV-2 modulates the host innate immune response for its evasion from host defense and its corresponding pathogenesis caused by cytokine storm. We emphasize Type I interferon response and the strategies of evading innate immune defense used by SARS-CoV-2. We also extensively discuss the cells and their function involved in the innate immune response and inflammatory response, as well as the promises and challenges of drugs targeting excessive inflammation for antiviral treatment. This review would help us to figure out the current challenge questions of SARS-CoV-2 infection on innate immunity and directions for future studies.

Accuracy and Timeliness of Knowledge Dissemination on COVID-19 Among People in Rural and Remote Regions of China at the Early Stage of Outbreak

Coronavirus disease 2019 (COVID-19) spread throughout China in January 2020. To contain the virus outbreak, the Chinese government took extraordinary measures in terms of public policy, wherein accurate and timely dissemination of information plays a crucial role. Despite all of the efforts toward studying this health emergency, little is known about the effectiveness of public policies that support health communication during such a crisis to disseminate knowledge for self-protection. Particularly, we focus on the accuracy and timeliness of knowledge dissemination on COVID-19 among people in remote regions—a topic largely omitted in existing research. In February 2020, at the early-stages of the COVID-19 outbreak, a questionnaire survey was carried out. In total, 8,520 participants from seven less economically developed provinces situated in the borderlands of China with large ethnic minority groups responded. We analyzed the data through poisson regression and logistic regression analyses. We found that (1) people in remote regions of China obtained accurate information on COVID-19. Further, they were able to take appropriate measures to protect themselves. (2) Result from both descriptive analysis and multivariable regression analysis revealed that there is no large difference in the accuracy of information among groups. (3) Older, less educated, and rural respondents received information with a significant delay, whereas highly educated, younger, urban residents and those who obtained information through online media were more likely to have received the news of the outbreak sooner and to be up to date on the information. This research provides evidence that disadvantage people in remote regions obtained accurate and essential information required to act in an appropriate manner in responses to the COVID-19 outbreak. However, they obtained knowledge on COVID-19 at a slower pace than other people;thus, further improvement in the timely dissemination of information among disadvantage people in remote regions is warranted.

Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus.

AIMS: Type 2 diabetes mellitus (T2DM) is a strong risk factor for complications of coronavirus disease 2019 (COVID-19). The effect of T2DM medications on COVID-19 outcomes remains unclear. In a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 in Wuhan, we have previously found that metformin use prior to hospitalization is associated with reduced mortality. The current study aims to investigate the effects of inpatient use of T2DM medications, including metformin, acarbose, insulin and sulfonylureas, on the mortality of COVID-19 patients with T2DM during hospitalization. METHODS: We continue to carry out a retrospective analysis of a cohort of 131 patients with T2DM hospitalized for COVID-19 and treated with different combinations of diabetes medications. RESULTS: We found that patients using metformin (p = .02) and acarbose (p = .04), alone or both together (p = .03), after admission were significantly more likely to survive than those who did not use either metformin or acarbose. 37 patients continued to take metformin after admission and 35 (94.6%) survived. Among the 57 patients who used acarbose after admission, 52 survived (91.2%). A total of 20 patients used both metformin and acarbose, while 57 used neither. Of the 20 dual-use patients, 19 (95.0%) survived. CONCLUSION: Our analyses suggest that inpatient use of metformin and acarbose together or alone during hospitalization should be studied in randomized trials.

Evaluating the mitigation strategies of COVID-19 by the application of the CO2 emission data through high-resolution agent-based computational experiments.

The negative consequences, such as healthy and environmental issues, brought by rapid urbanization and interactive human activities result in increasing social uncertainties, unreliable predictions, and poor management decisions. For instance, the Coronavirus Disease (COVID-19) occurred in 2019 has been plaguing many countries. Aiming at controlling the spread of COVID-19, countries around the world have adopted various mitigation and suppression strategies. However, how to comprehensively eva luate different mitigation strategies remains unexplored. To this end, based on the Artificial societies, Computational experiments, Parallel execution (ACP) approach, we proposed a system model, which clarifies the process to collect the necessary data and conduct large-scale computational experiments to evaluate the effectiveness of different mitigation strategies. Specifically, we established an artificial society of Wuhan city through geo-environment modeling, population modeling, contact behavior modeling, disease spread modeling and mitigation strategy modeling. Moreover, we established an evaluation model in terms of the control effects and economic costs of the mitigation strategy. With respect to the control effects, it is directly reflected by indicators such as the cumulative number of diseases and deaths, while the relationship between mitigation strategies and economic costs is built based on the CO2 emission. Finally, large-scale simulation experiments are conducted to evaluate the mitigation strategies of six countries. The results reveal that the more strict mitigation strategies achieve better control effects and less economic costs.

Discrimination and social exclusion in the outbreak of COVID-19

This paper is aimed to document the observed social exclusion and discrimination in the outbreak of COVID-19 across the world and inside of China. Discrimination and social exclusion has occurred in various forms, while 25.11% of respondents overseas experienced discrimination in the breakout of COVID-19, and 90% of respondents inside of China exhibited discriminatory attitudes. The discrimination and social exclusion also lead to a range of damaging social outcomes. Thus, this is an urgent call for the inclusiveness in policy and media in the face of this public health emergency.

Inflammasome Activation in Children With Kawasaki Disease and Multisystem Inflammatory Syndrome.

[Figure: see text].

Openness and COVID-19 induced xenophobia: The roles of trade and migration in sustainable development.

Along with the plight of the COVID-19 outbreak in 2020 come the xenophobic behaviors and hate crimes against people with Asian descent around the globe. The threat of a public health emergency catalyzed underlying xenophobic sentiments, manifesting them into racial discrimination of various degrees. With most discriminatory acts reported in liberal societies, this article investigates whether an economy more open to trade and migration can be more susceptible to xenophobia. Using our first-hand survey data of 1767 Chinese respondents residing overseas from 65 different countries during February of 2020, we adopt an instrumental variable strategy to identify the causal effect of openness to trade and migration of their residence country on the likelihood of them receiving discriminatory behaviors during the early stage of the COVID-19 outbreak. Our results show that greater openness to trade increases the likelihood of reported xenophobic behaviors, while openness to migration decreases it. On the other hand, stronger trade or immigration relationships with China are associated with less reported discrimination. And these effects primarily influence discriminatory behavior in interpersonal spaces, rather than through media outlets. Our findings highlight nuances of the effect of trade relations on the culture of a society.

Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19.

OBJECTIVE: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population. METHODS: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis. RESULTS: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort (P = .02). CONCLUSION: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM.

Epidemiological and clinical characteristics of 35 children with COVID-19 in Beijing, China.

IMPORTANCE: Within the coronavirus disease 2019 (COVID-19) global pandemic, more attention is warranted for whether this new infectious disease has unique manifestations in children. OBJECTIVE: To retrospectively determine the epidemiological and clinical characteristics of 35 children with COVID-19 in Beijing, China. METHODS: We collected data for 35 children diagnosed with COVID-19 who were admitted to Beijing Ditan Hospital from January 2020 to June 2020, and analyzed their epidemiological characteristics, clinical manifestations, laboratory examinations, chest imaging findings, treatments, and outcomes. RESULTS: The children comprised 18 boys (51.4%) and 17 girls (48.6%) aged 6 months to 15 years. All patients had clear epidemiological history, with family clusters accounting for 28 cases (80.0%) and clear tracing of exposure to high epidemic areas in the remaining 7 cases (20.0%). Four (11.4%) patients were classified as asymptomatic, 17 (48.6%) as acute upper respiratory infection, and 14 (40.0%) as mild pneumonia, with no severe or critical cases. Clinical manifestations were mild, including fever in 18 (51.4%), cough in 14 (40.0%), and nausea and diarrhea in 7 (20.0%) patients. White blood cell count was mostly normal (26 cases, 74.3%) or decreased (7 cases, 20.0%); lymphocyte percentage was increased in 24 (68.7%); neutrophil percentage was decreased in 25 (71.4%); alanine aminotransferase was increased in 3 (8.6%); and serum potassium was decreased in 4 (11.4%). Time to negative viral nucleic acid testing was 2-42 days (mean: 14.0 ± 9.4 days). Chest imaging examination revealed that 20 patients (57.1%) had different forms of lung inflammation. Treatment was mainly isolation and nutritional support. Eleven patients were treated with interferon atomization inhalation. No patients required oxygen therapy. All 35 children were cured and discharged. Length of hospital stay was 9-54 days (mean: 25.4 ± 13.8 days). During regular follow-up after discharge, 5 children showed positivity again in the viral nucleic acid test and were re-hospitalized for observation and treatment. The mean length of re-hospitalization stay was 10.8 days. INTERPRETATION: Children with COVID-19 mainly become infected within their family, and children of all ages are generally susceptible. The disease in children is mostly mild and the prognosis is good. Nucleic acid tests in some patients become positive again after discharge, suggesting that it is of great significance to carry out centralized isolation medical observations and active nucleic acid tests in close contacts for early detection of patients and routine epidemic prevention and control.

Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development.

Stress proteins (SPs) including heat-shock proteins (HSPs), RNA chaperones, and ER associated stress proteins are molecular chaperones essential for cellular homeostasis. The major functions of HSPs include chaperoning misfolded or unfolded polypeptides, protecting cells from toxic stress, and presenting immune and inflammatory cytokines. Regarded as a double-edged sword, HSPs also cooperate with numerous viruses and cancer cells to promote their survival. RNA chaperones are a group of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are essential factors for manipulating both the functions and metabolisms of pre-mRNAs/hnRNAs transcribed by RNA polymerase II. hnRNPs involve in a large number of cellular processes, including chromatin remodelling, transcription regulation, RNP assembly and stabilization, RNA export, virus replication, histone-like nucleoid structuring, and even intracellular immunity. Dysregulation of stress proteins is associated with many human diseases including human cancer, cardiovascular diseases, neurodegenerative diseases (e.g., Parkinson's diseases, Alzheimer disease), stroke and infectious diseases. In this review, we summarized the biologic function of stress proteins, and current progress on their mechanisms related to virus reproduction and diseases caused by virus infections. As SPs also attract a great interest as potential antiviral targets (e.g., COVID-19), we also discuss the present progress and challenges in this area of HSP-based drug development, as well as with compounds already under clinical evaluation.

Changes in Body Weight, Physical Activity, and Lifestyle During the Semi-lockdown Period After the Outbreak of COVID-19 in China: An Online Survey.

OBJECTIVES: The outbreak of novel coronavirus (COVID-19) provided an opportunity to undertake an online survey to study the relationships between body weight changes with changes in physical activity and lifestyle during an unusual event of forced isolation, or quarantine. METHODS: We distributed an electronic questionnaire using the popular social application WeChat to adults from any province of China except Hubei Province, the epicenter of the outbreak. The questionnaire asked for demographic information, body weight, physical activity, and lifestyle factors before and during the quarantine. RESULTS: Of 376 questionnaires returned, 339 were valid (90.2%). During the period of semi-lockdown, both females and males with BMI <24 gained weight, males with BMI ≥24 lost weight, and females with BMI ≥24 gained weight. The average steps per day and the average moderate or vigorous-intensity exercise declined significantly for both males and females during the semi-lockdown. Changes in body weight inversely correlated with changes in steps per day and moderate or vigorous-intensity exercise during the quarantine. CONCLUSIONS: Normal weight individuals, who are not normally troubled by overweight or obesity, had less awareness of weight gain than people with a BMI ≥ 24. Under the conditions of the semi-lockdown, they tended to gain weight.

Pandemic COVID-19: Current status and challenges of antiviral therapies.

The pandemic COVID-19, caused by a new coronavirus SARS-CoV-2 infection, has infected over 12 million individuals and caused more than 55,200 death worldwide. Currently, there is no specific drug to treating this disease. Here we summarized the mechanisms of antiviral therapies and the clinic findings from different countries. Antiviral chemotherapies have been conducted by in multiple cohorts in different counties. Although FDA has fast approved remdesivir for treating COVID-19, it only speeds up recovery from COVID-19 with mildly reduced mortality. The chloroquine was suggested a potential drug against SARS-CoV-2 infection due to its in vitro antiviral effects, it is imperative high-quality data from worldwide clinical trials are necessitated for an approved therapy. In terms of hydroxychloroquine (HCQ) therapy, although WHO has stopped all the clinic trials due to its strong side-effects in COVID patients, large scale clinical trials with a long-term outcome follow-up may warrant HCQ and azithromycin combination in combating the virus. Convalescent plasma (CP) therapy suggested its safety use in SARS-CoV-2 infection; but both CP immunotherapy and NK cellular therapy must be manufactured and utilized according to scrupulous ethical and controlled conditions to guarantee a possible role of these products of human origin. Further research should be conducted to define the exact mechanism of SARS-CoV-2 pathogenesis, suitable animal models or ex vivo human lung tissues aid in studying replication, transmission and spread of the novel viruses, thereby facilitating highly effective therapies.