Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge.

Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.

A tissue specific-infection mouse model of SARS-CoV-2.

Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.

To what extent do young chinese elites comply with COVID-19 prevention and control measures?

BACKGROUND: During the COVID-19 pandemic, it is vital for individuals to comply with the government's prevention and control measures. This study aims to explore determinants of college students' compliance behaviour during the COVID-19 pandemic. METHODS: This study conducted an online survey among 3,122 individuals aged 18 and above from March to November 2022 in China. Individuals' compliance behaviour was divided into protective behaviour (that includes wearing a mask, maintaining a physical distance, and getting vaccinated) and restrictive behaviour (that includes offering health codes and a nucleic acid test certificate). Individuals' compliance motivation was divided into calculated motivation (including the fear of being infected, the fear of being published, and previous experience of pandemic prevention) and normative motivation (including the sense of social responsibility and trust in government). We defined young people aged between 18 and 24 with a college degree as young elites, and constructed ordinary least squares linear regression to compare their compliance behaviour with young people without a college degree (young non-elites), and non-young people with a college degree (non-young elites). RESULTS: Almost three years after the outbreak of the pandemic, Chinese individuals retained a high degree of compliance with COVID-19 prevention and control policies, particularly with respect to the provision of health codes. Young elites were more compliant with getting vaccinated, wearing a mask, providing health codes and testing results than their counterparts. The sense of social responsibility and trust in government were the major drivers of young elites' compliance behaviour during the pandemic. Young elites who were male, had a rural "hukou", and were not a member of the China Communist Party were more compliant with COVID-19 prevention and control measures. CONCLUSION: This study found that young elites in China had high policy compliance during the COVID-19 pandemic. These young elites' compliance behaviour was driven by their sense of social responsibility and trust in government rather than the fear of being infected and the fear of being punished as a result of violating the regulations. We suggest that in the context of managing health crises, in stead of introducing punitive measures to enforce citizens to comply with the management measures, promoting citizens' sense of social responsibility and building a trusting relationship with citizens contrite to the enhancement of citizens' policy compliance.

Association of the awareness of the epidemic, mental health status with mobile phone screen use time in Chinese college students during COVID-19 isolation and control

Objective This study aimed to investigate the awareness of the epidemic among college students and their mental health as well as to explore the association between their awareness of the epidemic mental health and the daily mobile phone screen use time, in order to provide guidance for the publicity of school epidemic prevention and control knowledge and the psychological counseling of students. Methods A cross-sectional design was employed among 780 college students, The Pandemic Fatigue Questionnaire, epidemic prevention and control knowledge and the mental health Scale were used to collect data through an online survey. Results 1. Awareness rate of the transmission routes and protective measures of COVID-19 among college students is higher when the daily mobile screen use time is 3–7 hours. 2. 21.79% of the 780 college students felt stressed;24.87% felt anxious;19.23% showed depression. 3. The scores of each subscale in the daily mobile phone screen use time of 3–7 hours and more than 7 hours were higher, and the scores of each subscale in the group of more than 7 hours were the highest. Further correlation analysis found that the time spent on mobile phone screens was positively correlated with stress, anxiety, and depression scores (r = 0.155, 0.180, 0.182, P<0.01). Conclusion During the COVID-19 isolation and control period, college students with different mobile screen usage time have different understandings of the epidemic. Long-term mobile screen use is related to the occurrence of psychological problems such as stress, anxiety, and depression. Therefore, education departments and schools should pay attention to college students' mobile phone use time to reduce the occurrence of bad psychological state of students.

Clinical efficacy of Jingyin granules, a Chinese patent medicine, in treating patients infected with coronavirus disease 2019.

BACKGROUND: Jingyin granules (JY), one patented Chinese herbal formula, have been advised for treating coronavirus disease 2019 (COVID-19) in China. As of now, the safety and effectiveness of JY in treating COVID-19 patients were still to be evaluated. PURPOSE: To investigate the safety and clinical effectiveness of JY in treating mild COVID-19 patients. STUDY DESIGN: We carried out a prospective cohort study, as the highly infectious COVID-19 omicron variant ranged in Shanghai (ClinicalTrial.gov registration number: ChiCTR2200058692). METHODS: Participants infected with COVID-19, who were diagnosed as mild cases, were assigned to receive either JY (JY group) or traditional Chinese medicine placebo (placebo group) orally for 7 days. The primary clinical indicators were the RNA negative conversion rate (NCR) and the incidence of severe cases. The secondary clinical indicators were the negative conversion time (NCT), inpatient length of stay (ILOS), and the disappearance rates of clinical symptoms. RESULTS: Nine hundred participants were recruited in this clinical trial study, and 830 patients met the eligibility criteria. Seven hundred and ninety-one patients, accomplished the following-up assessment, including 423 cases of JY group and 368 cases of placebo group. NCR in JY group at 7-day posttreatment was considerably greater compared with placebo group (89.8% [380/423] vs 82.6% [304/368], P = 0.003). None of the patients with mild COVID-19 developed into severe cases. The median NCT of SARS-CoV-2 and ILOS in JY group were lesser than that in placebo group (4.0 [3.0,6.0]vs 5.0 [4.0,7.0] days, P < 0.001; 6.0 [4.0, 8.0] vs 7.0 [5.0, 9.0] days, P < 0.001). In both groups, the obvious improvement in clinical symptoms was observed, but the difference was not significant. In the subgroup of age ≤ 60 years, JY promoted SARS-CoV-2 RNA negative conversion (HR=1.242; 95% CI: 1.069-1.444, P < 0.001). No patients in both groups were reported as the case of serious adverse event. CONCLUSION: JY maybe the potential medicine for treating mild COVID-19 patients, which had beneficial effects on increasing NCR, and shortening NCT and ILOS.

SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2ZYG11B activity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNECs) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2ZYG11B to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.

Kangyi Qiangshen Gong exercise prescription for pulmonary function and quality of life in patients recovered from COVID-19: a study protocol for a randomized controlled trial.

BACKGROUND: Since early 2022, patients with 2019 novel coronavirus (COVID-19) infection have increased rapidly in Shanghai, China. Nevertheless, there is no widely used unified rehabilitation treatment available for discharged patients with post-infection sequelae such as dyspnea, depression, and fatigue. To promote the rehabilitation of discharged patients, our team formulated Kangyi Qiangshen Gong exercise prescription on the basis of traditional Chinese medicine rehabilitation exercises (TCMRE). We designed a randomized controlled trial to evaluate the efficacy of rehabilitation and advantages of KQG for discharged patients with post-COVID-19 syndrome. METHODS/DESIGN: This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. In total, 60 discharged patients with COVID-19 sequelae, aged from 20 to 80 years will be recruited and randomly assigned to the World Health Organization instructed breathing techniques (BT) group and the Kangyi Qiangshen Gong exercise prescription (KQG) group at a ratio of 1:1. The patients in the BT group will perform breathing techniques exercise, and the patients in the KQG group will perform KQG exercise. Both groups will perform exercises twice a day for 3 months. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Modified Borg Scale, Fatigue Scale-14, Patient Health Questionnaire-9 Scale, Pittsburgh Sleep Quality Index, and the Respiratory Symptoms Scale. Clinical scales will be assessed at three points (pre-exercise, 3 months post-exercise, and 3 months follow-up). Adverse events will be recorded for safety assessment. DISCUSSION: This trial will serve high-quality evidence of the value of KQG for treating discharged patients with COVID-19 in rehabilitation period. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200059504. Registered on 03 May 2022. DISSEMINATION: The results will be published in peer-reviewed journals and disseminated through the study's website, and conferences.

Traditional Chinese medicine for COVID-19 pandemic and emerging challenges: An online cross-sectional survey in China.

BACKGROUND: We aimed to investigate use of infection control behaviours, preventative and therapeutic interventions, and outcomes among respondents to an online survey during the COVID-19 pandemic in China. METHODS: The survey was designed by an international team, translated and adapted to simplified Chinese, including 132 kinds of traditional Chinese medicine (TCM) preparation recommended by guidelines. It was distributed and collected from February to May 2021, with data analysed by WPS spreadsheet and wjx.cn. Descriptive statistics were used to describe demographics and clinical characteristics, diagnosis, treatments, preventative behaviours and interventions, and their associated outcomes. RESULTS: The survey was accessed 503 times with 341 (67.8%) completions covering 23 provinces and four municipalities in China. Most (282/341, 82.7%) respondents reported no symptoms during the pandemic and the majority (290/341, 85.0%) reported having a SARS-CoV-2 PCR test at some point. Forty-five (13.2%) reported having a respiratory infection, among which 19 (42.2%) took one or more categories of modern medicine, e.g. painkillers, antibiotics; 16 (35.6%) used TCM interventions(s); while seven respondents combined TCM with modern medicine. All respondents reported using at least one behavioural or medical approach to prevention, with 22.3% taking TCM and 5.3% taking modern medicines. No respondents reported having a critical condition related to COVID-19. CONCLUSION: We found evidence of widespread use of infection control behaviours, modern medicines and TCM for treatment and prevention of COVID-19 and other respiratory symptoms. Larger scale studies are warranted, including a more representative sample exploring TCM preparations recommended in clinical guidelines.

A new conceptual model of experiences of aging in place in the United States: Results of a systematic review and meta-ethnography of qualitative studies.

OBJECTIVES: The purpose of this systematic review was to synthesize the evidence on experiences of aging in place in the United States. DESIGN: Systematic review and meta-ethnography of qualitative studies. DATA SOURCES: We searched six bibliographic databases (PubMed, Embase, PsycINFO, CINAHL, Web of Science, Sociological Abstracts), with no limits on publication date. Eligible studies reported peer-reviewed qualitative research on experiences of aging in place in the United States with full-text available in English. REVIEW METHODS: Three reviewers independently used Covidence software to screen titles and abstracts followed by full texts. We assessed quality and risk of bias using a modified version of the Joanna Briggs Institute Checklist for Qualitative Research. Qualitative data analysis was conducted using meta-ethnography, following Noblit and Hare's seven-step method of translation and synthesis to generate a novel conceptual model. RESULTS: Of 2659 papers screened, 37 unique studies were eligible for inclusion, reported in 38 publications. The studies were conducted in 16 states and published between 1994 and 2018. The included samples represented 1199 participants in total, with mean ages ranging from 48 to 91 years. The gender of the samples ranged from 20% to 100% female, with a median of 77%. One-third of the included studies did not report participants' race/ethnicity, and half of the remaining study samples were at least 90% white; however, 20% of the studies focused exclusively on experiences of racial/ethnic minority older adults. Using meta-ethnography, we developed a new conceptual model of aging in place in the United States as a dynamic process of balancing threats and agency in relation to experiences of identity, connectedness, and place. We found that people aging in place were engaged in significant work to cope with unpredictable needs and challenges by changing their mindset, adapting their home environment to accommodate new needs, and finding different ways to connect with important people in their lives. Agency was shaped by resources and restrictions on choice, and where threats to aging in place outweighed an individual's sense of agency, the consequences included feelings of uncertainty, isolation, and dislocation. CONCLUSIONS: To the best of our knowledge, this is the first systematic review of qualitative studies to evaluate experiences of aging in place in the United States. The findings of our meta-ethnographic synthesis led to the development of a new conceptual model of aging in place highlighting the dynamic tensions involved in balancing threats and agency.

Therapeutic effects and safety of oral Chinese patent medicine for COVID-19: A rapid systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Chinese patent medicine (CPM) is an indispensable part of traditional Chinese medicine. Coronavirus Disease 2019 (COVID-19) manifests is an acute respiratory infectious disease. This systematic review aimed to evaluate the therapeutic effects and safety of oral CPM for COVID-19. METHODS: We included randomized controlled trials (RCTs) that tested oral CPM for the treatment of COVID-19 identified from publications in CNKI, Wanfang, VIP, Web of Science, SinoMed, PubMed, Embase, BioRxiv, MedRxiv and arXiv before November 2nd, 2020. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool. RESULTS: Seven RCTs including 1079 participants were identified. The overall bias was assessed as "-high risk of bias" for all included trials. Oral CPM investigated were: Lianhua Qingwen capsule/granules (LHQW), Jinhua Qinggan granules (JHQG), Huoxiang Zhengqi dripping pills (HXZQ), Toujie Quwen granules (TJQW) and Lianhua Qingke granules (LHQK). Compared with conventional western therapy alone for people with COVID-19: regarding the main outcomes, the results showed that oral CPM combined with conventional western therapy improved cure rate (RR = 1.20, 95 % CI 1.04-1.38, involving LHQW and TJQW), reduced aggravation rate (RR = 0.50, 95 % CI 0.29 - 0.85, involving LHQW, JHQG, LHQK and TJQW); with regard to additional outcomes, the results showed that add-on oral CPM shortened the duration of fever, cough and fatigue, improved the recovery rate of cough and fatigue, and increased the improvement and recovery rate of chest CT manifestations. There were some differences in therapeutic effects among various CPMs for the same COVID-19 outcome. The use of TJQW and LHQG appeared not to increase the risk of adverse events, but JHQG may cause mild diarrhea. CONCLUSION: Low-certainty or very low-certainty evidence demonstrated that oral CPM may have add-on potential therapeutic effects for patients with non-serious COVID-19. These findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.

Thymosin as a possible therapeutic drug for COVID-19: A case report.

BACKGROUND: There are no effective antiviral therapies for coronavirus disease 2019 (COVID-19) at present. Although most patients with COVID-19 have a mild or moderate course of disease, up to 5%-10% of patients may have a serious and potentially life-threatening condition, indicating an urgent need for effective therapeutic drugs. The therapeutic effect of thymosin on COVID-19 has not been previously studied. In this paper, for the first time we report a case of thymosin treatment of COVID-19. CASE SUMMARY: A 51-year-old man with imported COVID-19 was admitted with definite symptoms of chest tightness, chest pain, and fatigue. The polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 were negative. The antibody test was positive, confirming the diagnosis of COVID-19. As many orally administered drugs were not well tolerated due to gastrointestinal symptoms, an emergency use of thymosin, a polypeptide consisting of 28 amino acids, was administered by injection. Finally, after the implementation of the treatment program, symptoms and lung imaging improved significantly. CONCLUSION: In this case report, it is confirmed that thymosin may help alleviate the severity of COVID-19 symptoms.

Research progress on influence of environmental factors on transmission of coronavirus disease 2019

The global pandemic of coronavirus disease 2019 (COVID-19) remains challenging as it shows no signs of abating in key countries, but resurgence in European and East Asian regions. On July 23, the cumulative number of confirmed cases worldwide exceeded 15 million. The coronavirus pandemic has rebounded in some parts of China. In particular, there many outbreaks of cluster infections at home and abroad recently and SARS-CoV-2 have been detected positive in multiple environment samples. The role of environmental factors in the transmission of COVID-19 has attracted widespread attention. This article summarized the research progress of various environmental factors[such as meteorological factors (temperature, humidity, and wind speed), contaminated water and drinking water, air, surfaces, food, food packages, and food processors, and insects] affecting the transmission of COVID-19, emphasizing that environmental sanitation is one of the keys to controlling rebound and large-scale transmission of the pandemic, and proposed corresponding prevention and control recommendations.

Acupressure therapy and Liu Zi Jue Qigong for pulmonary function and quality of life in patients with severe novel coronavirus pneumonia (COVID-19): a study protocol for a randomized controlled trial.

BACKGROUND: In December 2019, pneumonia associated with the 2019 novel coronavirus (COVID-19) emerged in Wuhan, China. The number of cases has increased rapidly. Patients with severe disease have a poor prognosis, and there are no effective therapies for COVID-19. Only rapid advice guidelines for symptomatic supportive care have been used. A traditional Chinese medicine rehabilitation (TCMR) program consisting of acupressure therapy and Liu Zi Jue Qigong can be used as a complementary therapy for COVID-19. Hence, we designed a randomized trial to evaluate the efficacy and advantages of TCMR for treating patients with severe COVID-19. METHODS/DESIGN: This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. A total of 128 patients with COVID-19 aged from 20 to 80 years will be recruited and assigned randomly into a guideline therapy group and a guideline therapy plus TCMR group at a 1:1 ratio. Patients in both groups will receive guideline therapy. The patients in the intervention group will perform acupressure therapy and Liu Zi Jue Qigong exercises in addition to conventional treatments twice a day and will be persistent from admission to discharge. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Activities of Daily Living Barthel Index Scale, Patient Health Questionnaire-9 Scale, and the Respiratory Symptoms Scale. The assessments of the clinical scales will be performed at three points (before treatment, the 7th day during hospitalization, and the discharge day). Adverse events will be noted and recorded for the safety evaluation. DISCUSSION: This trial will provide high-quality evidence of the value of TCMR, which consists of acupressure therapy and Liu Zi Jue Qigong exercises, for treating patients with severe COVID-19. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000029994 . Registered on 18 February 2020.

SARS, MERS and COVID-19 among healthcare workers: A narrative review.

In the recent two decades, three global viral infectious diseases, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and coronavirus disease (COVID-19), have occurred worldwide. SARS occurred in November 2002, causing 8096 infected cases, as well as 774 deaths. MERS occurred in June, 2012, causing 2519 confirmed cases, along with 866 associated deaths. COVID-19 occurred in December 2019, as of 30 April 2020, a total of 3,024,059 clinical cases have been reported, including 208,112 deaths. Healthcare workers (HCWs) need to be in close contact with these virus-infected patients and their contaminated environments at work, thus leading to be infected in some of them, even a few of them are died in line of duty. In this review, we summarized the infection status of HCWs during the outbreak of SARS, MERS and COVID-19, with in-depth discussion, hoping to provoke sufficient attention to the HCWs infection status by more people.

Efficacy of Liu-zi-jue in Patients with 2019 Novel Coronavirus Pneumonia (COVID-19): structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: Efficacy of conventional treatment plus the complementary therapy Liu-zi-jue (a mind-body exercise) to treat patients with mild COVID-19. TRIAL DESIGN: The study is a single-center 2 arm, randomized controlled trial with parallel-group design.