Erratum: Inhaled ACE2-engineered microfluidic microsphere for intratracheal neutralization of COVID-19 and calming of the cytokine storm.

[This corrects the article DOI: 10.1016/j.matt.2021.09.022.].

Fe-Fe Double-Atom Catalysts for Murine Coronavirus Disinfection: Nonradical Activation of Peroxides and Mechanisms of Virus Inactivation.

Peroxides find broad applications for disinfecting environmental pathogens particularly in the COVID-19 pandemic; however, the extensive use of chemical disinfectants can threaten human health and ecosystems. To achieve robust and sustainable disinfection with minimal adverse impacts, we developed Fe single-atom and Fe-Fe double-atom catalysts for activating peroxymonosulfate (PMS). The Fe-Fe double-atom catalyst supported on sulfur-doped graphitic carbon nitride outperformed other catalysts for oxidation, and it activated PMS likely through a nonradical route of catalyst-mediated electron transfer. This Fe-Fe double-atom catalyst enhanced PMS disinfection kinetics for inactivating murine coronaviruses (i.e., murine hepatitis virus strain A59 (MHV-A59)) by 2.17-4.60 times when compared to PMS treatment alone in diverse environmental media including simulated saliva and freshwater. The molecular-level mechanism of MHV-A59 inactivation was also elucidated. Fe-Fe double-atom catalysis promoted the damage of not only viral proteins and genomes but also internalization, a key step of virus lifecycle in host cells, for enhancing the potency of PMS disinfection. For the first time, our study advances double-atom catalysis for environmental pathogen control and provides fundamental insights of murine coronavirus disinfection. Our work paves a new avenue of leveraging advanced materials for improving disinfection, sanitation, and hygiene practices and protecting public health.

Factors Associated With Long COVID Symptoms in an Online Cohort Study.

Background: Few prospective studies of Long COVID risk factors have been conducted. The purpose of this study was to determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are associated with Long COVID. Methods: In March 26, 2020, the COVID-19 Citizen Science study, an online cohort study, began enrolling participants with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection. Adult participants who reported a positive SARS-CoV-2 test result before April 4, 2022 were surveyed for Long COVID symptoms. The primary outcome was at least 1 prevalent Long COVID symptom greater than 1 month after acute infection. Exposures of interest included age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, variant wave, number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, and exercise. Results: Of 13 305 participants who reported a SARS-CoV-2 positive test, 1480 (11.1%) responded. Respondents' mean age was 53 and 1017 (69%) were female. Four hundred seventy-six (32.2%) participants reported Long COVID symptoms at a median 360 days after infection. In multivariable models, number of acute symptoms (odds ratio [OR], 1.30 per symptom; 95% confidence interval [CI], 1.20-1.40), lower socioeconomic status/financial insecurity (OR, 1.62; 95% CI, 1.02-2.63), preinfection depression (OR, 1.08; 95% CI, 1.01-1.16), and earlier variants (OR = 0.37 for Omicron compared with ancestral strain; 95% CI, 0.15-0.90) were associated with Long COVID symptoms. Conclusions: Variant wave, severity of acute infection, lower socioeconomic status, and pre-existing depression are associated with Long COVID symptoms.

A Single-Administration Microneedle Skin Patch for Multi-Burst Release of Vaccine against SARS-CoV-2.

The necessity for multiple injections and cold-chain storage has contributed to suboptimal vaccine utilization, especially in pandemic situations. Thermally-stable and single-administration vaccines hold a great potential to revolutionize the global immunization process. Here, a new approach to thermally stabilize protein-based antigens is presented and a new high-throughput antigen-loading process is devised to create a single-administration, pulsatile-release microneedle (MN) patch which can deliver a recombinant SARS-CoV-2 S1-RBD protein-a model for the COVID-19 vaccine. Nearly 100% of the protein antigen could be stabilized at temperatures up to 100 °C for at least 1 h and at an average human body temperature (37 °C) for up to 4 months. Arrays of the stabilized S1-RBD formulations can be loaded into the MN shells via a single-alignment assembly step. The fabricated MNs are administered at a single time into the skin of rats and induce antibody response which could neutralize authentic SARS-CoV-2 viruses, providing similar immunogenic effect to that induced by multiple bolus injections of the same antigen stored in conventional cold-chain conditions. The MN system presented herein could offer the key solution to global immunization campaigns by avoiding low patient compliance, the requirement for cold-chain storage, and the need for multiple booster injections.

Application of the PDCA Cycle for Managing Hyperglycemia in Critically Ill Patients.

INTRODUCTION: Stress hyperglycemia is a common symptom in critically ill patients, and is not only a marker indicating the severity of illness but is also related to worsening outcomes. Managing stress hyperglycemia without increasing the likelihood of hypoglycemia is one of the most pressing challenges to be urgently addressed in clinics. The Plan-Do-Check-Act (PDCA) cycle management has been put forward in various surgical management scenarios, and has proven to be effective in the diagnosis and treatment of different diseases. It possesses dynamic characteristics and can be updated according to the results of glycemic control and feedback. This study focused on the use of PDCA to manage glucose levels in critically ill patients. METHODS: Based on the glucose level of 1003 critically ill patients admitted to the emergency intensive care unit (EICU) from 1 October 2019 to 31 December 2020, we collected and matched the prevalence of hyperglycemia, hypoglycemia, and glucose variability on a quarterly basis. According to the PDCA management method, we analyzed the possible causes, supervised the implementation of measures, summarized the feedback on improvements, and then proposed new improvement measures for implementation in the next quarter. RESULTS: Three measures were proposed and applied to enhance the management of hyperglycemia: (I) Updating and formulating three editions of the insulin infusion protocol and increasing the initial and maintenance doses of insulin on a case-by-case basis; (II) reducing the use of parenteral nutrition and ensuring that enteral nutrition is consumed at a uniform and slow rate; and (III) forming a training method during the COVID-19 pandemic and improving implementation of the insulin infusion protocol. Following PDCA management, the prevalence of hyperglycemia fell from 43.18% to 32.61%, the incidence of hypoglycemia was below 1.00%, and there was no significant fluctuation in blood glucose variability. CONCLUSION: The PDCA method is helpful in developing a superior insulin infusion protocol for critically ill patients and lowering the prevalence of hyperglycemia in critically ill patients.

The Effects of Race/Ethnicity, Age, and Area Deprivation Index (ADI) on COVID-19 Disease Early Dynamics: Washington, D.C. Case Study.

The COVID-19 pandemic and its associated mitigation strategies have significant psychosocial, behavioral, socioeconomic, and health impacts, particularly in vulnerable US populations. Different factors have been identified as influencers of the transmission rate; however, the effects of area deprivation index (as a measure of social determinants of health, SDoH) as a factor on COVID-19 disease early dynamics have not been established. We determined the effects of area deprivation index (ADI) and demographic factors on COVID-19 outcomes in Washington, D.C. This retrospective study used publicly available data on COVID-19 cases and mortality of Washington, D.C., during March 31st-July 4th, 2020. The main predictors included area deprivation index (ADI), age, and race/ethnicity. The ADI of each census block groups in D.C. (n=433) were obtained from Neighborhood Atlas map. Using a machine learning-based algorithm, the outcome variables were partitioned into time intervals: time duration (Pi, days), rate of change coefficient (Ei), and time segment load (Pi×Ei) for transmission rate and mortality. Correlation analysis and multiple linear regression models were used to determine associations between predictors and outcome variables. COVID-19 early transmission rate (E1) was highly correlated with ADI (SDoH; r= 0.88, p=0.0044) of the Washington, D.C. community. We also found positive association between ADI, age (0-17 years, r=0.91, p=0.0019), and race (African American/Black, r=0.86; p=0.0068) and COVID-19 outcomes. There was high variability in early transmission across the geographic regions (i.e., wards) of Washington, D.C., and this variability was driven by race/ethnic composition and ADI. Understanding the association of COVID-19 disease early transmission and mortality dynamics and key socio-demographic risk factors such as age, race, and ADI, as a measure of social determinants, will contribute to health equity/equality and distribution of economic resources/assistance and is essential for future predictive modeling of the COVID-19 pandemic to limit morbidity and mortality.

What Matters Most: A Needs Assessment of Older Adults

Introduction With aging, comes a myriad of new experiences and adversities. One theme that continuously presents itself, especially in mental health clinics, is loneliness and isolation. The lack of social connections and the hinderance it plays only became more apparent during the COVID-19 pandemic and prompted the idea of creating a psychotherapeutic intervention to help combat these experiences in older adults. Group interventions foster social connections while reducing cost and the limited access to clinicians;the overall aim of this project was to conduct a program evaluation of an innovative, rotating psychological wellness group for older adults. In keeping with this, a needs assessment of what matters most in older adults was performed. Methods This pilot program includes a psychological wellness group offering for older adults with 6 modules covering a collection of topics that support optimal psychological wellness and promote health and resilience (i.e. digital tools and mobile apps, value-based behavioral activation to improve your mood, eating for a healthy brain, introduction to mindfulness, improving your sleep and strategies for managing anxiety) that are be held weekly, ranging in duration from 2-6 weeks, over the next 6 months. Participants were referred from outpatient psychiatry clinics, geriatric medicine providers in medical center, and local community organizations servicing older adults. To be included, patients had to be 65+ years old, English speaking, open to group treatment, and without a diagnosis of dementia. Once participants were triaged and selected, a questionnaire was sent that addressed multiple aspects of their past medical history as well as their goals of care, prompting patients to identify what matters most to them in the domains of functionality, enjoyment, and connectivity as well as an open text question allowing them to expand on which three matter the most above all. Results Older adults (N=21) were enrolled in the psychological wellness group, including 6 males and 15 females. Seven of the participants lived alone and 3 were caregivers. Survey results indicated that older adults greatly prioritize maintaining cognitive status as their greatest health priority. The perceived importance of maintaining social connectivity via relationships with family and friends was rated equally if not higher than physical functionality. The following representative direct patient quotes encapsulate this sentiment well with "[I] just can't seem to connect. I spend most of my days alone trying to make meaningful connection.” "Spend time with family and friends (personal connections, they are important to me).” Relatedly, patients who indicated that mental cognition was not one of their most important health goals tended to respond positively to priorities centered around personal independence, such as travel, preserved sensory function, and ability to complete iADLs. However, ability to care for self and others was globally the least important priority. Conclusions Insights in the health priorities of older adults may allow for a better understanding of their treatment goals, allowing for greater alignment in the therapeutic alliance. Of the neurocognitive domains, social cognition is not routinely tested;this preliminary data underscores the importance of this domain to older adults. Future work includes collecting additional surveys to create datasets large enough for cluster analysis and predictive modeling, which may be informative for directing targeted modules in expected areas of need and in initial intake triage. This research was funded by Psychiatry Innovator Grants Program- Grant #1266204-705-KAVGS Department of Psychiatry and Behavioral Sciences, Stanford University (PI: Cassidy-Eagle).

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Functional studies of HLA and its role in SARS-CoV-2: Stimulating T cell response and vaccine development.

In the biological immune process, the major histocompatibility complex (MHC) plays an indispensable role in the expression of HLA molecules in the human body when viral infection activates the T-cell response to remove the virus. Since the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2019, how to address and prevent SARS-CoV-2 has become a common problem facing all mankind. The T-cell immune response activated by MHC peptides is a way to construct a defense line and reduce the transmission and harm of the virus. Presentation of SARS-CoV-2 antigen is associated with different types of HLA phenotypes, and different HLA phenotypes induce different immune responses. The prediction of SARS-CoV-2 mutation information and the design of vaccines based on HLAs can effectively activate autoimmunity and cope with virus mutations, which can provide some references for the prevention and treatment of SARS-CoV-2.

Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea virus strains circulating in China from 2020 to 2021.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, has become the major causative agent of acute gastroenteritis in piglets since 2010 in China. RESULTS: In the current study, 91 complete spike (S) gene sequences were obtained from PEDV positive samples collected from 17 provinces in China from March 2020 to March 2021. A phylogenetic analysis showed that 92.3% (84 out of 91) of the identified strains belonged to GII subtype, while 7.7% (7 out of 91) were categorized as S-INDEL like strains and grouped within GI-c clade. Based on a recombination analysis, six of S-INDEL like strains were recombinant strains originated from S-INDEL strain FR/001/2014 and virulent strain AJ1102. In addition, PEDV variant strains (CH/GDMM/202012, CH/GXDX/202010 et al) carrying novel insertions (360QGRKS364 and 1278VDVF1281) in the S protein were observed. Furthermore, the deduced amino acid sequences for the S protein showed that multiple amino acid substitutions in the antigenic epitopes in comparison with the vaccine strains. CONCLUSIONS: In conclusion, these data provide novel molecular evidence on the epidemiology and molecular diversity of PEDV in 2020-2021. This information may help design a strategy for controlling and preventing the prevalence of PEDV variant strains in China.

Creating a Patient-Based Diagnostic Checklist for Functional Tics During the COVID-19 Pandemic.

Background and Objectives: Since the onset of the COVID-19 pandemic, there has been a dramatic change in the presentation of patients with tics. The explosive presentation of atypical tics (TT) has been noted worldwide and thought to be the manifestation of a pandemic-associated functional neurologic disorder following social media exposure to tics. Nevertheless, despite the frequent diagnosis of functional tics (FT), there are no existing formal diagnostic criteria. The primary aim of this study was to create a patient-based diagnostic checklist for making the diagnosis of a functional tic disorder (FTD) during the COVID-19 pandemic. Methods: A retrospective chart review at a single institution during the pandemic was performed. Based on the available literature, diagnostic criteria were created for TT, FT, and patients with dramatically evolving symptoms (i.e., mixed with prior history of mild tics with later fulminant functional worsening). Patient demographics, comorbidities, and tic characteristics of these groups were then compared. Following initial assessments, new diagnostic criteria were established and statistically reanalyzed. Results: One hundred ninety-eight patients underwent investigation. Significant differences in age, sex, psychological comorbidities, tic characteristics, and tic severity were found between patients with TT when compared with either of the 2 the functional groups. Only the presence of rostrocaudal progression and increased obsessive-compulsive behaviors were significantly different between patients with new-onset FT and those with functional worsening of a previous tic disorder. Results also showed that age at tic onset was not a contributing factor for group differentiation. Many patients with FT were not exposed to videos depicting tics on social media. Discussion: This study confirms the presence of a distinct presentation of aTT during the pandemic period. It further establishes the validity of specific criteria useful in dividing patients with tics into 3 formal diagnostic criteria: (1) primary tic disorders (PTDs), (2) a strictly FTD, and (3) a mixed tic disorder consisting of patients with an initial history of a PTD and the later development of FT. Explicit diagnostic criteria should enable clinicians and researchers to make a definitive identification and assist patients and families become more knowledgeable and accepting of the diagnosis of FT.

A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2.

The development of safe and effective vaccines to respond to COVID-19 pandemic/endemic remains a priority. We developed a novel subunit protein-peptide COVID-19 vaccine candidate (UB-612) composed of: (i) receptor binding domain of SARS-CoV-2 spike protein fused to a modified single-chain human IgG1 Fc; (ii) five synthetic peptides incorporating conserved helper and cytotoxic T lymphocyte (Th/CTL) epitopes derived from SARS-CoV-2 structural proteins (three from S2 subunit, one from membrane and one from nucleocapsid), and one universal Th peptide; (iii) aluminum phosphate as adjuvant. The immunogenicity and protective immunity induced by UB-612 vaccine were evaluated in four animal models: Sprague-Dawley rats, AAV-hACE2 transduced BALB/c mice, rhesus and cynomolgus macaques. UB-612 vaccine induced high levels of neutralizing antibody and T-cell responses, in all animals. The immune sera from vaccinated animals neutralized the SARS-CoV-2 original wild-type strains and multiple variants of concern, including Delta and Omicron. The vaccination significantly reduced viral loads, lung pathology scores, and disease progression after intranasal and intratracheal challenge with SARS-CoV-2 in mice, rhesus and cynomolgus macaques. UB-612 has been tested in primary regimens in Phase 1 and Phase 2 clinical studies and is currently being evaluated in a global pivotal Phase 3 clinical study as a single dose heterologous booster.

The U.S. COVID-19 County Policy Database: a novel resource to support pandemic-related research.

BACKGROUND: It is increasingly recognized that policies have played a role in both alleviating and exacerbating the health and economic consequences of the COVID-19 pandemic. There has been limited systematic evaluation of variation in U.S. local COVID-19-related policies. This study introduces the U.S. COVID-19 County Policy (UCCP) Database, whose objective is to systematically gather, characterize, and assess variation in U.S. county-level COVID-19-related policies. METHODS: In January-March 2021, we collected an initial wave of cross-sectional data from government and media websites for 171 counties in 7 states on 22 county-level COVID-19-related policies within 3 policy domains that are likely to affect health: (1) containment/closure, (2) economic support, and (3) public health. We characterized the presence and comprehensiveness of policies using univariate analyses. We also examined the correlation of policies with one another using bivariate Spearman's correlations. Finally, we examined geographical variation in policies across and within states. RESULTS: There was substantial variation in the presence and comprehensiveness of county policies during January-March 2021. For containment and closure policies, the percent of counties with no restrictions ranged from 0% (for public events) to more than half for public transportation (67.8%), hair salons (52.6%), and religious gatherings (52.0%). For economic policies, 76.6% of counties had housing support, while 64.9% had utility relief. For public health policies, most were comprehensive, with 70.8% of counties having coordinated public information campaigns, and 66.7% requiring masks outside the home at all times. Correlations between containment and closure policies tended to be positive and moderate (i.e., coefficients 0.4-0.59). There was variation within and across states in the number and comprehensiveness of policies. CONCLUSIONS: This study introduces the UCCP Database, presenting granular data on local governments' responses to the COVID-19 pandemic. We documented substantial variation within and across states on a wide range of policies at a single point in time. By making these data publicly available, this study supports future research that can leverage this database to examine how policies contributed to and continue to influence pandemic-related health and socioeconomic outcomes and disparities. The UCCP database is available online and will include additional time points for 2020-2021 and additional counties nationwide.

PEDV: Insights and Advances into Types, Function, Structure, and Receptor Recognition.

Porcine epidemic diarrhea virus (PEDV) has been endemic in most parts of the world since its emergence in the 1970s. It infects the small intestine and intestinal villous cells, spreads rapidly, and causes infectious intestinal disease characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and causing massive economic losses to the pig industry. The entry of PEDV into cells is mediated by the binding of its spike protein (S protein) to a host cell receptor. Here, we review the structure of PEDV, its strains, and the structure and function of the S protein shared by coronaviruses, and summarize the progress of research on possible host cell receptors since the discovery of PEDV.

The Dynamic Effects of Urban–Rural Income Inequality on Sustainable Economic Growth under Urbanization and Monetary Policy in China

Income inequality in China has become increasingly serious since the beginning of the economic reform period in the 1970s, with urban–rural income inequality playing a large role. Urbanization policy and monetary policy are currently important economic policy tools for the Chinese government. In order to investigate the influence of inequality on the economy and to provide recommendations for ensuring the sustainability of growth, we study the effect of urban–rural income inequality on economic growth in the context of urbanization and monetary policy in China between 2002 and 2021. Using a flexible time-varying parametric structural vector auto-regression (TVP-VAR) model and a robust Markov chain Monte Carlo (MCMC) algorithm, our empirical results show that the effect is time-varying, with inequality promoting growth in the early years but affecting it adversely at later stages. Currently, urbanization mitigates inequality and promotes growth simultaneously, while easy monetary policy worsens inequality and affects growth adversely in the long term. We suggest that the authorities need to consider the implementation of policy rebalancing to ensure that the sustainability of economic development is not jeopardized because of worsening income disparity. Proactive urbanization policy and prudent monetary policy are viable rebalancing options.

A Bibliometric Analysis of Risk Management in Foreign Direct Investment: Insights and Implications

Aiming to identify the intellectual structure of risk management in foreign direct investment and its evolving trends, this paper introduces bibliometric analysis to systematically review the 1231 articles published between 1995 and 2022. Through the analysis of publication trends, influential indicators, cooperative networks, and citations, we draw the following important conclusions. From 1995 to 2021, the average annual growth rate of scientific production in the field reached 21.4%, with scholars from the United States and China contributing the most. Regarding the cooperation network, its structure is relatively dispersed, and the deep cooperation among a wide range of researchers has not yet been formed. As for research topics, the popularity of interest in environmental protection, carbon dioxide emissions, energy consumption, and climate change has increased significantly in recent years. Moreover, this paper points out that future research directions include new risks and challenges posed by the COVID-19 pandemic and the effects of climate risks on foreign direct investment. These results are helpful for scholars to systematically understand the current research status, research frontiers, and future trends of risk management in foreign direct investment.

A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants.

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.

Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants (preprint)

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

Prevalence of dry eye disease among Chinese high school students during the COVID-19 outbreak.

PURPOSE: The study aimed to investigate the prevalence of dry eye disease (DED) and relevant risk factors among Chinese high school students during the COVID-19 outbreak. METHODS: A cross-sectional study was conducted from November to December 2020, and 4825 high school students from nine high schools in Shanghai were recruited. All students completed ocular surface disease index (OSDI) and perceived stress scale (PSS) questionnaires and answered other questions designed to ascertain information on the risk factors related to DED. DED was diagnosed when OSDI scores were greater than or equal to 13. The prevalence of symptomatic DED was determined. A T-test, Kruskal-Wallis test, Chi-square test, and logistic regression analysis were used to examine the possible risk factors. RESULTS: The prevalence of symptomatic DED among Chinese high school students was 70.5%. In univariate analysis, higher PSS scores (P<0.001), prolonged video display terminal (VDT) use (P<0.001), wearing contact lenses (P=0.001), poor sleep quality (P<0.001), and being female (P<0.001) were significantly correlated with dry eyes. In multivariate logistic regression analysis, higher PSS scores (P<0.001, OR=1.20), prolonged VDT use (P<0.001, OR=1.07), poor sleep quality (P<0.001, OR=1.84), and being female (P=0.001, OR=1.25) were significant risk factors associated with DED. CONCLUSIONS: Due to the epidemic, most Chinese high school students are in a high-risk environment in which they are more likely to suffer from DED, such as long online courses and heavy stress from school. Relevant preventive measures that may have a positive impact on public health and quality of life for high school students should be brought to the forefront.

Serum 8-Hydroxydeoxyguanosine Is a Potential Indicator for the Severity and Prognosis in Patients with Community-Acquired Pneumonia: A Prospective Cohort Study.

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.