Palliative care for cancer patients during the COVID-19 pandemic: A narrative synthesis from 36 studies of 16 countries.

BACKGROUND: During the COVID-19 epidemic, palliative care has become even more indispensable for cancer patients. AIM: To identify the changes in palliative care for cancer patients and improvements in palliative care quality during the COVID-19 pandemic. DESIGN: A systematic review and narrative synthesis was conducted in PubMed, Embase and Web of Science. An evaluation tool using mixed methods was used to assess the quality of the study. The main relevant themes identified were used to group qualitative and quantitative findings. RESULTS: A total of 36 studies were identified, primarily from different countries, with a total of 14,427 patients, 238 caregivers and 354 health care providers. Cancer palliative care has been experiencing several difficulties following the COVID-19 pandemic, including increased mortality and infection rates as well as delays in patient treatment that have resulted in poorer prognoses. Treatment providers are seeking solutions such as electronic management of patients and integration of resources to care for the mental health of patients and staff. Telemedicine plays an important role in many ways but cannot completely replace traditional treatment. Clinicians strive to meet patients' palliative care needs during special times and improve their quality of life. CONCLUSIONS: Palliative care faces unique challenges during the COVID-19 epidemic. With adequate support to alleviate care-related challenges, patients in the home versus hospital setting will be able to receive better palliative care. In addition, this review highlights the importance of multiparty collaboration to achieve personal and societal benefits of palliative care. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Clinical outcomes of the severe acute respiratory syndrome coronavirus 2 Omicron and Delta variant: systematic review and meta-analysis of 33 studies covering 6 037 144 coronavirus disease 2019-positive patients.

BACKGROUND: Although the SARS-CoV-2 Omicron variant is considered to induce less severe disease, there have been no consistent results on the extent of the decrease in severity. OBJECTIVES: To compare the clinical outcomes of COVID-19-positive patients with Omicron and Delta variant infection. DATA SOURCES: Searches were implemented up to 8 November 2022 in PubMed, Web of Science, BioRvix, and MedRvix. STUDY ELIGIBILITY CRITERIA: Eligible studies were cohort studies reporting the clinical outcomes of COVID-19-positive patients with Omicron and Delta variant infection, including hospitalization, intensive care unit (ICU) admission, receiving invasive mechanical ventilation (IMV), and death. PARTICIPANTS: COVID-19-positive patients with Omicron and Delta variant infection. ASSESSMENT OF RISK OF BIAS: Risk of bias was assessed employing the Newcastle-Ottawa Scale. METHODS OF DATA SYNTHESIS: Random-effect models were employed to pool the ORs and 95% CIs to compare the risk of clinical outcome. I2 was employed to evaluate the heterogeneity between studies. RESULTS: A total of 33 studies with 6 037 144 COVID-19-positive patients were included in this meta-analysis. In the general population of COVID-19-positive patients, compared with Delta, Omicron variant infection resulted in a decreased risk of hospitalization (10.24% vs. 4.14%, OR = 2.91, 95% CI = 2.35-3.60), ICU admission (3.67% vs. 0.48%, OR = 3.64, 95% CI = 2.63-5.04), receiving IMV (3.93% vs. 0.34%, OR = 3.11, 95% CI = 1.76-5.50), and death (2.40% vs. 0.46%, OR = 2.97, 95% CI = 2.17-4.08). In the hospitalized patients with COVID-19, compared with Delta, Omicron variant infection resulted in a decreased risk of ICU admission (20.70% vs. 12.90%, OR = 1.63, 95% CI = 1.32-2.02), receiving IMV (10.90% vs. 5.80%, OR = 1.65, 95% CI = 1.28-2.14), and death (10.72% vs. 7.10%, OR = 1.44, 95% CI = 1.22-1.71). CONCLUSIONS: Compared with Delta, the severity of Omicron variant infection decreased.

COVID-19 pandemic increases the occurrence of nursing burnout syndrome: an interrupted time-series analysis of preliminary data from 38 countries.

AIM: To evaluate the trends in nursing burnout rates before and during the coronavirus 2019 restrictions. METHOD: Meta-analysis was used to extract the data on global nursing burnout from 1 Jan. 2010-15 Dec. 2022. An interrupted time-series analysis using segmented ordinary least squares (OLS) regression models was used to explore if the nursing burnout were affected by the epidemic. Newey-West standard error was used to adjust for autocorrelation and heteroskedasticity. RESULTS: Before the epidemic (April 2020), the nursing burnout rate rose with 0.0007497 (95% CI: 0.0000316, 0.0014677, t = 2.07, P = 0.041) per month. The trend of nursing burnout rate has increased by 0.0231042 (95 CI%:0.0086818, 0.0375266, t = 3.18, P = 0.002). The increasing trend of nursing burnout rate after the COVID-19 restrictions is 0.0007497 + 0.0231042 = 0.0238539 per month. CONCLUSION: The study indicated that the Covid-19 restrictions had an impact on nursing burnout, increasing the occurrence of nursing burnout syndrome.

Community-Level Social Support to Mitigate the Impact of Combined Frailty and Multimorbidity on Psychological Distress Among Rural Chinese Older Adults During the COVID-19 Pandemic: Multilevel Modeling Study.

BACKGROUND: Accumulating research provides evidence that the psychological health of older people deteriorated from before to during the COVID-19 pandemic. Unlike robust individuals, coexisting frailty and multimorbidity expose older adults to more complicated and wide-ranging stressors. Community-level social support (CSS) is also an important impetus for age-friendly interventions, and it is 1 of the components of social capital that is seen as an ecological-level property. To date, we have not found research that examines whether CSS buffered the adverse impacts of combined frailty and multimorbidity on psychological distress in a rural setting during COVID-19 in China. OBJECTIVE: This study explores the combined effect of frailty and multimorbidity on psychological distress in rural Chinese older adults during the COVID-19 pandemic and examines whether CSS would buffer the aforementioned association. METHODS: Data used in this study were extracted from 2 waves of the Shandong Rural Elderly Health Cohort (SREHC), and the final analytic sample included 2785 respondents who participated in both baseline and follow-up surveys. Multilevel linear mixed effects models were used to quantify the strength of the longitudinal association between frailty and multimorbidity combinations and psychological distress using 2 waves of data for each participant, and then, cross-level interactions between CSS and combined frailty and multimorbidity were included to test whether CSS would buffer the adverse impact of coexisting frailty and multimorbidity on psychological distress. RESULTS: Frail older adults with multimorbidity reported the most psychological distress compared to individuals with only 1 or none of the conditions (ß=.68, 95% CI 0.60-0.77, P<.001), and baseline coexisting frailty and multimorbidity predicted the most psychological distress during the COVID-19 pandemic (ß=.32, 95% CI 0.22-0.43, P<.001). Further, CSS moderated the aforementioned association (ß=-.16, 95% CI -0.23 to -0.09, P<.001), and increased CSS buffered the adverse effect of coexisting frailty and multimorbidity on psychological distress during the COVID-19 pandemic (ß=-.11, 95% CI -0.22 to -0.01, P=.035). CONCLUSIONS: Our findings suggest that more public health and clinical attention should be paid to psychological distress among multimorbid older adults with frailty when facing public health emergencies. This research also suggests that community-level interventions prioritizing social support mechanisms, specifically improving the average levels of social support within communities, may be an effective approach to alleviate psychological distress for rural older adults who concurrently manifest frailty and multimorbidity.

A bispecific nanobody dimer broadly neutralizes SARS-CoV-1 & 2 variants of concern and offers substantial protection against Omicron via low-dose intranasal administration.

Current SARS-CoV-2 Omicron subvariants impose a heavy burden on global health systems by evading immunity from most developed neutralizing antibodies and vaccines. Here, we identified a nanobody (aSA3) that strongly cross-reacts with the receptor binding domain (RBD) of both SARS-CoV-1 and wild-type (WT) SARS-CoV-2. The dimeric construct of aSA3 (aSA3-Fc) tightly binds and potently neutralizes both SARS-CoV-1 and WT SARS-CoV-2. Based on X-ray crystallography, we engineered a bispecific nanobody dimer (2-3-Fc) by fusing aSA3-Fc to aRBD-2, a previously identified broad-spectrum nanobody targeting an RBD epitope distinct from aSA3. 2-3-Fc exhibits single-digit ng/mL neutralizing potency against all major variants of concerns including BA.5. In hamsters, a single systemic dose of 2-3-Fc at 10 mg/kg conferred substantial efficacy against Omicron infection. More importantly, even at three low doses of 0.5 mg/kg, 2-3-Fc prophylactically administered through the intranasal route drastically reduced viral RNA loads and completely eliminated infectious Omicron particles in the trachea and lungs. Finally, we discovered that 2(Y29G)-3-Fc containing a Y29G substitution in aRBD-2 showed better activity than 2-3-Fc in neutralizing BA.2.75, a recent Omicron subvariant that emerged in India. This study expands the arsenal against SARS-CoV-1, provides potential therapeutic and prophylactic candidates that fully cover major SARS-CoV-2 variants, and may offer a simple preventive approach against Omicron and its subvariants.

Mental distress, quality of life and physical symptoms in Chinese women with ovarian cancer receiving olaparib treatment during the COVID-19 pandemic.

Objectives: Women with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib. Methods: The survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL. Results: A total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress. Conclusions: This study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic.

Mental distress, quality of life and physical symptoms in Chinese women with ovarian cancer receiving olaparib treatment during the COVID-19 pandemic

Objectives Women with ovarian cancer (OC) have experienced unprecedented challenges since the novel coronavirus disease-2019 (COVID-19) outbreak in China. We aim to evaluate the experience of psychological status, physical symptoms and quality of life (QoL) and investigate the impact of COVID-19 pandemic on OC patients receiving olaparib. Methods The survey was conducted online from April 22 to May 12 in 2020. Demographic and clinical questions were listed to collect general information. The degree of insomnia, depression, anxiety, stress symptoms and QoL were assessed by the Chinese versions of the Insomnia Severity Index, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the General Functional Assessment of Cancer Therapy, respectively. Multivariate logistic regression analysis was conducted to analyze the risk factors for mental distress and QoL. Results A total of 56 respondents coming from 15 various provinces in China participated in the survey. The prevalence of insomnia, depressive, anxiety, stress symptoms and reduced QoL were 37.5, 51.8, 37.5, 30.4, and 51.8%, respectively. Unfavorable disease status, shorter period of olaparib administration, adverse events of olaparib and delay in cancer care were correlated with mental health problems. Reduced QoL was also significantly associated with psychological distress. Conclusions This study emphasized that mental health problems and reduced QoL should gain more attention in women with OC who are receiving oral olaparib at home. Appropriate psychological healthcare strategies are necessary for OC patients during the COVID-19 pandemic.

A DNA-based non-infectious replicon system to study SARS-CoV-2 RNA synthesis.

The coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously affected public health around the world. In-depth studies on the pathogenic mechanisms of SARS-CoV-2 is urgently necessary for pandemic prevention. However, most laboratory studies on SARS-CoV-2 have to be carried out in bio-safety level 3 (BSL-3) laboratories, greatly restricting the progress of relevant experiments. In this study, we used a bacterial artificial chromosome (BAC) method to assemble a SARS-CoV-2 replication and transcription system in Vero E6 cells without virion envelope formation, thus avoiding the risk of coronavirus exposure. Furthermore, an improved real-time quantitative reverse transcription PCR (RT-qPCR) approach was used to distinguish the replication of full-length replicon RNAs and transcription of subgenomic RNAs (sgRNAs). Using the SARS-CoV-2 replicon, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 facilitates the transcription of sgRNAs in the discontinuous synthesis process. Moreover, two high-frequency mutants of N protein, R203K and S194L, can obviously enhance the transcription level of the replicon, hinting that these mutations likely allow SARS-CoV-2 to spread and reproduce more quickly. In addition, remdesivir and chloroquine, two well-known drugs demonstrated to be effective against coronavirus in previous studies, also inhibited the transcription of our replicon, indicating the potential applications of this system in antiviral drug discovery. Overall, we developed a bio-safe and valuable replicon system of SARS-CoV-2 that is useful to study the mechanisms of viral RNA synthesis and has potential in novel antiviral drug screening.

Family Doctor Contract Services and Awareness of Blood Pressure Measurement Among Hypertension Patients: A Cross-Sectional Study in Rural Shandong, China.

Background: Some studies found that family doctor contract services (FDCSs) had positive impact on the self-measurement behaviors of hypertension patients. However, evidence concerning the association between FDCSs and blood pressure measurement awareness among hypertension patients is not clear. Objective: This study aims to explore the relationship between FDCSs and blood pressure measurement awareness among the hypertension patients, and examine whether there is a difference in this relationship among middle-aged and aged adults in rural Shandong, China. Methods: A multi-stage stratified random sampling was adopted in 2018 in Shandong Province to conduct a questionnaire survey among the sample residents, in which 982 hypertension patients were included in the study. Pearson chi-square test and logistic regression model were employed using SPSS 24.0 to explore the association between FDCSs and blood pressure measurement awareness. Results: 76.8% of hypertension patients would measure blood pressure regularly. The blood pressure measurement awareness of the signing group was significantly higher than that of the non-signing group when controlling other variables (P < 0.001, OR = 2.075, 95% CI 1.391-3.095). The interaction of age and contracting status were significantly correlated with blood pressure measurement awareness (P = 0.042, OR = 1.747, 95% CI 1.020-2.992; P = 0.019, OR = 2.060, 95% CI 1.129-3.759). Factors including gender (P = 0.011, OR = 0.499, 95% CI 0.291-0.855), household income (P = 0.031, OR = 1.764, 95% CI 1.052-2.956), smoking status (P = 0.002, OR = 0.439, 95% CI 0.260-0.739), sports habits (P < 0.001, OR = 2.338, 95% CI 1.679-3.257), self-reported health (P = 0.031, OR = 1.608, 95% CI 1.043-2.477), distance to the village clinic (P = 0.006, OR = 1.952, 95% CI 1.208-3.153) and medications (P < 0.001, OR = 3.345, 95% CI 2.282-4.904) were also found to be associated with the blood pressure measurement awareness of hypertension patients. Conclusion: The government should take efforts to strengthen publicity and education of family doctors and pay more attention to uncontracted, middle-aged, female patients and patients with unhealthy life behaviors to improve the blood pressure measurement awareness.

Establishing and evaluating physician-pharmacist collaborative clinics to manage patients with type 2 diabetes in primary hospitals in Hunan province: study protocol of a multi-site randomized controlled trial in the era of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has exerted an unprecedented and universal impact on global health system, resulting in noticeable challenges in traditional chronic disease care, of which diabetes was reported to be most influenced by the reduction in healthcare resources in the pandemic. China has the world's largest diabetes population, and current diabetes management in China is unsatisfactory, particularly in rural areas. Studies in developed countries have demonstrated that physician-pharmacist collaborative clinics are efficient and cost-effective for diabetes management, but little is known if this mode could be adapted in primary hospitals in China. The aim of this proposed study is to develop and evaluate physician-pharmacist collaborative clinics to manage type 2 diabetes mellitus (T2DM) in primary hospitals in Hunan province. METHODS: A multi-site randomized controlled trial will be conducted to evaluate the effectiveness and cost-effectiveness of the physician-pharmacist collaborative clinics compared with usual care for Chinese patients with T2DM. Six primary hospitals will participate in the study, which will recruit 600 eligible patients. Patients in the intervention group will receive services from both physicians and pharmacists in the collaborative clinics, while the control group will receive usual care from physicians. Patients will be followed up at the 3rd, 6th, 9th and 12th month. Comparison between the two groups will be conducted by assessing the clinical parameters, process indicators and costs on diabetes. A satisfaction survey will also be carried out at the end of the study. DISCUSSION: If effective, the physician-pharmacist collaborative clinics can be adapted and used in primary hospitals of China to improve glycemic control, enhance medication adherence, decrease incidence of complications and reduce patients' dependence on physicians. Findings from the present study are meaningful for developing evidence-based diabetes care policy in rural China, especially in the COVID-19 pandemic era. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031839 , Registered 12 April 2020.

Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial.

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.

Risk Factors of Psychological Responses of Chinese University Students During the COVID-19 Outbreak: Cross-sectional Web-Based Survey Study.

BACKGROUND: COVID-19 is a highly contagious and highly pathogenic disease caused by a novel coronavirus, SARS-CoV-2, and it has become a pandemic. As a vulnerable population, university students are at high risk during the epidemic, as they have high mobility and often overlook the severity of the disease because they receive incomplete information about the epidemic. In addition to the risk of death from infection, the epidemic has placed substantial psychological pressure on the public. In this respect, university students are more prone to psychological problems induced by the epidemic compared to the general population because for most students, university life is their first time outside the structure of the family, and their mental development is still immature. Internal and external expectations and academic stress lead to excessive pressure on students, and unhealthy lifestyles also deteriorate their mental health. The outbreak of COVID-19 was a significant social event, and it could potentially have a great impact on the life and the mental health of university students. Therefore, it is of importance to investigate university students' mental health status during the outbreak of COVID-19. OBJECTIVE: The principal objective of this study was to investigate the influencing factors of the psychological responses of Chinese university students during the COVID-19 outbreak. METHODS: This study used data from a survey conducted in China between February 21 and 24, 2020, and the data set contains demographic information and psychological measures including the Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the compulsive behaviors portion of the Yale-Brown Obsessive-Compulsive Scale. A total of 2284 questionnaires were returned, and 2270 of them were valid and were used for analysis. The Mann-Whitney U test for two independent samples and binary logistic regression models were used for statistical analysis. RESULTS: Our study surveyed 563 medical students and 1707 nonmedical students. Among them, 251/2270 students (11.06%) had mental health issues. The results showed that contact history of similar infectious disease (odds ratio [OR] 3.363, P=.02), past medical history (OR 3.282, P<.001), and compulsive behaviors (OR 3.525, P<.001) contributed to the risk of mental health issues. Older students (OR 0.928, P=.02), regular daily life during the epidemic outbreak (OR 0.410, P<.001), exercise during the epidemic outbreak (OR 0.456, P<.001), and concern related to COVID-19 (OR 0.638, P=.002) were protective factors for mental health issues. CONCLUSIONS: According to the study results, mental health issues have seriously affected university students, and our results are beneficial for identifying groups of university students who are at risk for possible mental health issues so that universities and families can prevent or intervene in the development of potential mental health issues at the early stage of their development.

Pulling-Force Spinning Top for Serum Separation Combined with Paper-Based Microfluidic Devices in COVID-19 ELISA Diagnosis.

The spread of Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), resulting in a global pandemic with around four million deaths. Although there are a variety of nucleic acid-based tests for detecting SARS-CoV-2, these methods have a relatively high cost and require expensive supporting equipment. To overcome these limitations and improve the efficiency of SARS-CoV-2 diagnosis, we developed a microfluidic platform that collected serum by a pulling-force spinning top and paper-based microfluidic enzyme-linked immunosorbent assay (ELISA) for quantitative IgA/IgM/IgG measurements in an instrument-free way. We further validated the paper-based microfluidic ELISA analysis of SARS-CoV-2 receptor-binding domain (RBD)-specific IgA/IgM/IgG antibodies from human blood samples as a good measurement with higher sensitivity compared with traditional IgM/IgG detection (99.7% vs 95.6%) for early illness onset patients. In conclusion, we provide an alternative solution for the diagnosis of SARS-CoV-2 in a portable manner by this smart integration of pulling-force spinning top and paper-based microfluidic immunoassay.

How do government subsidies promote new energy vehicle diffusion in the complex network context? A three-stage evolutionary game model.

In order to cope with the impact of current coronavirus disease 2019 (COVID-19), the continued extension of financial subsidy period for new energy vehicles at the national level is a strong measure to support the sustainable development of new energy vehicle (NEV) industry. This paper further explores the promotion impact of government subsidies on NEV diffusion, and establishes a three-stage evolutionary game model. Based on the actual application, the NEV diffusion process is simulated in four kinds of authoritative networks. Results show that: (1) in the scale-free network, the subsidy rate must be high enough to promote full NEV diffusion, and the larger the network scale, the higher the threshold of subsidy rate; (2) in the small-world network, the larger the network scale, the more beneficial it is for full NEV diffusion; (3) for the small-scale network, topological characteristics have little effect on NEV diffusion depth, and only affect the speed when NEV diffusion reaches the stable state; (4) for the large-scale network, NEV diffusion in the scale-free network is more sensitive to the subsidy rate than that in the small-world network; (5) network topologies influencing NEV diffusion can be divided into two priorities. Finally, relevant policy recommendations are presented.

Management and implementation strategies of pre-screening triage in children during coronavirus disease 2019 pandemic in Guangzhou, China.

BACKGROUND: Emerging infectious diseases are a constant threat to the public's health and health care systems around the world. Coronavirus disease 2019 (COVID-2019), which was defined by the World Health Organization as pandemic, has rapidly emerged as a global health threat. Outbreak evolution and prevention of international implications require substantial flexibility of frontline health care facilities in their response. AIM: To explore the effect of the implementation and management strategy of pre-screening triage in children during COVID-19. METHODS: The standardized triage screening procedures included a standardized triage screening questionnaire, setup of pre-screening triage station, multi-point temperature monitoring, extensive screenings, and two-way protection. In order to ensure the implementation of the pre-screening triage, the prevention and control management strategies included training, emergency exercise, and staff protection. Statistical analysis was performed on the data from all the children hospitalized from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. Data were obtained from questionnaires and electronic medical record systems. RESULTS: A total of 17561 children, including 2652 who met the criteria for screening, 192 suspected cases, and two confirmed cases without omission, were screened from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. There was zero transmission of the infection to any medical staff. CONCLUSION: The effective strategies for pre-screening triage have an essential role in the prevention and control of hospital infection.

An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19.

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.

Changes in psychological distress before and during the COVID-19 pandemic among older adults: the contribution of frailty transitions and multimorbidity.

AIM: To investigate changes in psychological distress in community-dwelling older adults before and during the coronavirus disease 2019 (COVID-19) pandemic and the contribution of frailty transitions and multimorbidity in predicting the psychological distress. METHODS: Prospective repeated-measures cohort study on a sample of participants aged 60 and over. A total of 2, 785 respondents at the baseline (May 2019) were followed during the COVID-19 (August 2020). The changes in psychological distress before and during the COVID-19 were assessed using generalised estimation equations with adjusting for sex, age, education, economic status, marital status, tea drinking status, smoking status, alcohol drinking status, sedentary time, sleep quality and activities of daily living. RESULTS: The psychological distress of older people has significantly increased in August 2020 compared with May 2019. Both older adults who remained frail and transitioned into frail state reported more psychological distress during the COVID-19. Similarly, both pre-existing multimorbidity and emerging multimorbidity groups were associated with more psychological distress. The group of frailty progression who reported new emerging multimorbidity showed more increase in psychological distress in comparison with those who remained in the non-frail state who reported no multimorbidity. CONCLUSION: Psychological distress has increased among the community-dwelling older adults during the COVID-19 pandemic, and sustained and progressive frail states as well as multimorbidity were all associated with a greater increase of psychological distress. These findings suggest that future public health measures should take into account the increased psychological distress among older people during the COVID-19 pandemic, and the assessment of frailty and multimorbidity might help in warning of psychological distress.

Potent Neutralization of SARS-CoV-2 by Hetero-bivalent Alpaca Nanobodies Targeting the Spike Receptor-Binding Domain.

Cell entry by SARS-CoV-2 requires the binding between the receptor-binding domain (RBD) of the viral Spike protein and the cellular angiotensin-converting enzyme 2 (ACE2). As such, RBD has become the major target for vaccine development, while RBD-specific antibodies are pursued as therapeutics. Here, we report the development and characterization of SARS-CoV-2 RBD-specific VHH/nanobody (Nb) from immunized alpacas. Seven RBD-specific Nbs with high stability were identified using phage display. They bind to SARS-CoV-2 RBD with affinity KD ranging from 2.6 to 113 nM, and six of them can block RBD-ACE2 interaction. The fusion of the Nbs with IgG1 Fc resulted in homodimers with greatly improved RBD-binding affinities (KD ranging from 72.7 pM to 4.5 nM) and nanomolar RBD-ACE2 blocking abilities. Furthermore, the fusion of two Nbs with non-overlapping epitopes resulted in hetero-bivalent Nbs, namely aRBD-2-5 and aRBD-2-7, with significantly higher RBD binding affinities (KD of 59.2 pM and 0.25 nM) and greatly enhanced SARS-CoV-2 neutralizing potency. The 50% neutralization dose (ND50) of aRBD-2-5 and aRBD-2-7 was 1.22 ng/mL (∼0.043 nM) and 3.18 ng/mL (∼0.111 nM), respectively. These high-affinity SARS-CoV-2 blocking Nbs could be further developed into therapeutics as well as diagnostic reagents for COVID-19.ImportanceTo date, SARS-CoV-2 has caused tremendous loss of human life and economic output worldwide. Although a few COVID-19 vaccines have been approved in several countries, the development of effective therapeutics, including SARS-CoV-2 targeting antibodies, remains critical. Due to their small size (13-15 kDa), high solubility, and stability, Nbs are particularly well suited for pulmonary delivery and more amenable to engineer into multivalent formats than the conventional antibody. Here, we report a series of new anti-SARS-CoV-2 Nbs isolated from immunized alpaca and two engineered hetero-bivalent Nbs. These potent neutralizing Nbs showed promise as potential therapeutics against COVID-19.