Future COVID-19 Booster Vaccine Refusal in Healthcare Workers after a Massive Breakthrough Infection Wave, a Nationwide Survey-Based Study.

Background: An unprecedented coronavirus disease 2019 (COVID-19) wave occurred in China between December 2022 and January 2023, challenging the efficacy of the primary series of COVID-19 vaccines. The attitudes toward future COVID-19 booster vaccines (CBV) after the massive breakthrough infection among healthcare workers remain unknown. This study aimed to explore the prevalence and determinants of future CBV refusal after the unprecedented COVID-19 wave among healthcare workers. Methods: Between 9 and 19 February 2023, a cross-sectional nationwide online survey was conducted using a self-administered questionnaire vaccine among healthcare workers in China. Sociodemographics, profession, presence of chronic medical conditions, previous COVID-19 infection, attitudes towards future CBV, and reasons for future CBV refusal were collected. We estimated odds ratio [OR] with 95% confidence interval [CI] using a multivariable logistic regression model to explore the factors associated with future CBV refusal. Results: Among the 1618 participants who completed the survey, 1511 respondents with two or more doses of COVID-19 vaccines were analyzed. A total of 648 (41.8%) of respondents were unwilling to receive a future CBV. Multivariable logistic regression analysis revealed the association of CBV refusal with profession (vs. other staff, physician-adjusted OR 1.17, 95%CI 0.79-1.72, nurse-adjusted OR 1.88, 95%CI 1.24-2.85, p = 0.008), history of allergy (adjusted OR 1.72, 95%CI 1.05-2.83, p = 0.032), a lower self-perceived risk of future COVID-19 infection (p < 0.001), and a lower belief in CBV effectiveness (p = 0.014), safety (p < 0.001), and necessities for healthcare workers and the public (p < 0.001, respectively). Conclusions: Our findings highlight that a considerable proportion of healthcare workers were against a future booster dose after an unprecedented COVID-19 wave. Self-perception of future COVID-19 risk, and potential harm or doubtful efficacy of vaccines are the main determinants. Our findings may help public health authorities to establish future COVID-19 vaccination programs.

SARS-CoV-2 RdRp uses NDPs as a substrate and is able to incorporate NHC into RNA from diphosphate form molnupiravir.

The coronavirus disease 2019 has been ravaging throughout the world for three years and has severely impaired both human health and the economy. The causative agent, severe acute respiratory syndrome coronavirus 2 employs the viral RNA dependent RNA polymerase (RdRp) complex for genome replication and transcription, making RdRp an appealing target for antiviral drug development. Systematic characterization of RdRp will undoubtedly aid in the development of antiviral drugs targeting RdRp. Here, our research reveals that RdRp can recognize and utilize nucleoside diphosphates as a substrate to synthesize RNA with an efficiency of about two thirds of using nucleoside triphosphates as a substrate. Nucleoside diphosphates incorporation is also template-specific and has high fidelity. Moreover, RdRp can incorporate ß-d-N4-hydroxycytidine into RNA while using diphosphate form molnupiravir as a substrate. This incorporation results in genome mutation and virus death. It is also observed that diphosphate form molnupiravir is a better substrate for RdRp than the triphosphate form molnupiravir, presenting a new strategy for drug design.

Did lockdown influence bystanders' willingness to perform cardiopulmonary resuscitation? A worldwide registry-based perspective.

AIM: Bystander cardiopulmonary resuscitation (CPR) significantly increases the survival rate after out-of-hospital cardiac arrest. Using population-based registries, we investigated the impact of lockdown due to Covid-19 on the provision of bystander CPR, taking background changes over time into consideration. METHODS: Using a registry network, we invited all registries capable of delivering data from 1. January 2017 to 31. December 2020 to participate in this study. We used negative binominal regression for the analysis of the overall results. We also calculated the rates for bystander CPR. For every participating registry, we analysed the incidence per 100000 inhabitants of bystander CPR and EMS-treated patients using Poisson regression, including time trends. RESULTS: Twenty-six established OHCA registries reported 742 923 cardiac arrest patients over a four-year period covering 1.3 billion person-years. We found large variations in the reported incidence between and within continents. There was an increase in the incidence of bystander CPR of almost 5% per year. The lockdown in March/April 2020 did not impact this trend. The increase in the rate of bystander CPR was also seen when analysing data on a continental level. We found large variations in incidence of bystander CPR before and after lockdown when analysing data on a registry level. CONCLUSION: There was a steady increase in bystander CPR from 2017 to 2020, not associated with an increase in the number of ambulance-treated cardiac arrest patients. We did not find an association between lockdown and bystanders' willingness to start CPR before ambulance arrival, but we found inconsistent patterns of changes between registries.

The efficacy and safety of SARS-CoV-2 vaccines mRNA1273 and BNT162b2 might be complicated by rampant C-to-U RNA editing.

The SARS-CoV-2 RNA vaccines are smartly designed to increase the synonymous codon usage by introducing multiple U-to-C mutations. This design would elevate the translation efficiency of vaccine RNAs. However, we found evidence to reason that the designed cytidines might be converted to uridines again by C-to-U RNA deamination in host cells. This C-to-U mechanism might be a main factor that affects the efficacy and safety of RNA vaccines.

Benchmarking emergency department prediction models with machine learning and public electronic health records.

The demand for emergency department (ED) services is increasing across the globe, particularly during the current COVID-19 pandemic. Clinical triage and risk assessment have become increasingly challenging due to the shortage of medical resources and the strain on hospital infrastructure caused by the pandemic. As a result of the widespread use of electronic health records (EHRs), we now have access to a vast amount of clinical data, which allows us to develop prediction models and decision support systems to address these challenges. To date, there is no widely accepted clinical prediction benchmark related to the ED based on large-scale public EHRs. An open-source benchmark data platform would streamline research workflows by eliminating cumbersome data preprocessing, and facilitate comparisons among different studies and methodologies. Based on the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database, we created a benchmark dataset and proposed three clinical prediction benchmarks. This study provides future researchers with insights, suggestions, and protocols for managing data and developing predictive tools for emergency care.

The Role of Drones in Out-of-Hospital Cardiac Arrest: A Scoping Review.

Drones may be able to deliver automated external defibrillators (AEDs) directly to bystanders of out-of-hospital cardiac arrest (OHCA) events, improving survival outcomes by facilitating early defibrillation. We aimed to provide an overview of the available literature on the role and impact of drones in AED delivery in OHCA. We conducted this scoping review using the PRISMA-ScR and Arksey and O'Malley framework, and systematically searched five bibliographical databases (Medline, EMBASE, Cochrane CENTRAL, PsychInfo and Scopus) from inception until 28 February 2022. After excluding duplicate articles, title/abstract screening followed by full text review was conducted by three independent authors. Data from the included articles were abstracted and analysed, with a focus on potential time savings of drone networks in delivering AEDs in OHCA, and factors that influence its implementation. Out of the 26 included studies, 23 conducted simulations or physical trials to optimise drone network configuration and evaluate time savings from drone delivery of AEDs, compared to the current emergency medical services (EMS), along with 1 prospective trial conducted in Sweden and 2 qualitative studies. Improvements in response times varied across the studies, with greater time savings in rural areas. However, emergency call to AED attachment time was not reduced in the sole prospective study and a South Korean study that accounted for weather and topography. With growing interest in drones and their potential use in AED delivery spurring new research in the field, our included studies demonstrate the potential advantages of unmanned aerial vehicle (UAV) network implementation in controlled environments to deliver AEDs faster than current EMS. However, for these time savings to translate to reduced times to defibrillation and improvement in OHCA outcomes, careful evaluation and addressing of real-world delays, challenges, and barriers to drone use in AED delivery is required.

Management of Out-of-Hospital Cardiac Arrest during COVID-19: A Tale of Two Cities.

Variations in the impact of the COVID-19 pandemic on out-of-hospital cardiac arrest (OHCA) have been reported. We aimed to, using population-based registries, compare community response, Emergency Medical Services (EMS) interventions and outcomes of adult, EMS-treated, non-traumatic OHCA in Singapore and metropolitan Atlanta, before and during the pandemic. Associations of OHCA characteristics, pre-hospital interventions and pandemic with survival to hospital discharge were analyzed using logistic regression. There were 2084 cases during the pandemic (17 weeks from the first confirmed COVID-19 case) and 1900 in the pre-pandemic period (corresponding weeks in 2019). Compared to Atlanta, OHCAs in Singapore were older, received more bystander interventions (cardiopulmonary resuscitation (CPR): 65.0% vs. 41.4%; automated external defibrillator application: 28.6% vs. 10.1%), yet had lower survival (5.6% vs. 8.1%). Compared to the pre-pandemic period, OHCAs in Singapore and Atlanta occurred more at home (adjusted odds ratio (aOR) 2.05 and 2.03, respectively) and were transported less to hospitals (aOR 0.59 and 0.36, respectively) during the pandemic. Singapore reported more witnessed OHCAs (aOR 1.96) yet less bystander CPR (aOR 0.81) during pandemic, but not Atlanta (p < 0.05). The impact of COVID-19 on OHCA outcomes did not differ between cities. Changes in OHCA characteristics and management during the pandemic, and differences between Singapore and Atlanta were likely the result of systemic and sociocultural factors.

Flexible workspace providers as tenants: an analysis of the rental prices in the London market

Purpose>The covenant strength of flexible workspace (FW) providers as tenants is debatable. There is the argument that providers are risky mainly due to the very nature of their business which consists of volatile revenue streams obtained from subletting the space in membership format, paying little attention to covenants. On the other hand, there is also the argument that the presence of a provider can add vibrancy and diversity to a building whilst also offering an additional amenity to existing tenants through overflow space, making FW providers desirable. This paper aims to explore this ambiguity by comparing rents paid by FW providers and other tenants within the same building in London over the period 2011 to 2021.Design/methodology/approach>Using a dataset of 1,042 leases in London over the period of 2011–2021 which was extracted from CoStar, the rent conditions of FW providers and their peers within the same building were analysed employing a hedonic pricing model.Findings>The results of the analysis suggest that FW providers have a negative and statistically significant effect on the effective rent in comparison to other tenants within the same building over the analysed period.Practical implications>This analysis has the potential to identify how FW providers are perceived in the market and offers both academics and practitioners valuable insights.Originality/value>The relationship between landlords and FW providers as tenants does not have a major coverage in the literature.

Association Between Previous Stroke and Severe COVID-19: A Retrospective Cohort Study and an Overall Review of Meta-Analysis.

Objective: The objective of this study was to investigate the association between previous stroke and the risk of severe coronavirus disease 2019 (COVID-19). Methods: We included 164 (61.8 ± 13.6 years) patients with COVID-19 in a retrospective study. We evaluated the unadjusted and adjusted associations between previous stroke and severe COVID-19, using a Cox regression model. We conducted an overall review of systematic review and meta-analysis to investigate the relationship of previous stroke with the unfavorable COVID-19 outcomes. Results: The rate of severe COVID-19 in patients with previous stroke was 28.37 per 1,000 patient days (95% confidence interval [CI]: 10.65-75.59), compared to 3.94 per 1,000 patient days (95% CI: 2.66-5.82) in those without previous stroke (p < 0.001). Previous stroke was significantly associated with severe COVID-19 using a Cox regression model (unadjusted [hazard ratio, HR]: 6.98, 95% CI: 2.42-20.16, p < 0.001; adjusted HR [per additional 10 years]: 4.62, 95% CI: 1.52-14.04, p = 0.007). An overall review of systematic review and meta-analysis showed that previous stroke was significantly associated with severe COVID-19, mortality, need for intensive care unit admission, use of mechanical ventilation, and an unfavorable composite outcome. Conclusion: Previous stroke seems to influence the course of COVID-19 infection; such patients are at high risk of severe COVID-19 and might benefit from early hospital treatment measures and preventive strategies.

Industry herding in crypto assets

The aim of this paper is to investigate if herd behaviour is present in crypto assets at industry level. Using price information extracted from coinmarketcap.com between 29 April 2013 and 9 May 2022, we find evidence of herding and reverse herding in the crypto assets market. Concentrated periods of herding and reverse herding are particularly evident in the January 2020–April 2022 Covid period. At industry level, herding is more profound in large sectors with higher volatility. In smaller sectors where ventures are backed by ‘real assets’, very short periods of herding with marginal significance are detected. Reverse herding is present in all industries except Real Estate between June 2021 and May 2022, implying that strategies such as excessive ‘flight to quality’ or/and token picking are at play during the recent crypto crash. We also detect varying asymmetric herding at industry level. This paper further examines the factors that drive such industry herding and reverse herding in the crypto assets market, and our results show that industry concentration and investor sentiments contribute to the probability of herding/reverse herding. Our study provides further insights to the forces that drive the dispersion in crypto assets prices and contribute to the behavioural studies of the crypto market.

Should patients with epilepsy be vaccinated against coronavirus disease 2019? A systematic review and meta-analysis.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccination coverage, willingness, and safety profiles in patients with epilepsy remain poorly understood. We aimed to summarize the available evidence of COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. METHODS: We performed a literature search in the Pubmed, EMBASE, and Cochrane Central Register database between 1 January 2020 and 30 April 2022. We included eligible studies that provided information on the COVID-19 vaccination coverage, willingness, and safety profiles among patients with epilepsy. We investigated the association between baseline characteristics of patients with epilepsy and unvaccination status using a fixed-effect model. We calculated the pooled overall willingness to be vaccinated against COVID-19. We systematically reviewed the safety profiles after COVID-19 vaccination in patients with epilepsy. RESULTS: Ten eligible observational studies and two case reports yielded 2589 participants with epilepsy or their caregivers. Among 2145 participants that provided the information of vaccination status, 1508 (70.3%) patients with epilepsy were not administered COVID-19 vaccine, and 58% (95%CI 40-75%) of respondents were willing to be vaccinated against COVID-19. Seizure status (active versus inactive, OR 1.84 95%CI 1.41-2.39, I2 = 0%) rather than seizure type (focal versus non-focal, OR 1.22 95%CI 0.94-1.58, I2 = 0%) was associated with COVID-19 unvaccination status. Vaccines were well-tolerated; epilepsy-related problems such as increase in seizure frequency and status epilepticus after COVID-19 vaccination were uncommon. CONCLUSIONS: Our findings suggest a low COVID-19 vaccination coverage and willingness in patients with epilepsy. Vaccination against COVID-19 appears to be well-tolerated and safe in patients with epilepsy, supporting a positive outlook toward vaccination in this population.

Comparison of reverse-transcription qPCR and droplet digital PCR for the detection of SARS-CoV-2 in clinical specimens of hospitalized patients.

Accurate detection of severe acute respiratory syndrome coronavirus 2 is not only necessary for viral load monitoring to optimize treatment in hospitalized coronavirus disease 2019 patients, but also critical for deciding whether the patient could be discharged without any risk of viral shedding. Digital droplet PCR (ddPCR) is more sensitive than reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and is usually considered the superior choice. In the current study, we compared the clinical performance of RT-qPCR and ddPCR using oropharyngeal swab samples from patients hospitalized in the temporary Huoshenshan Hospital, Wuhan, Hubei, China. Results demonstrated that ddPCR was indeed more sensitive than RT-qPCR. Negative results might be caused by poor sampling technique or recovered patients, as the range of viral load in these patients varied significantly. In addition, both methods were highly correlated in terms of their ability to detect all three target genes as well as the ratio of copies of viral genes to that of the IC gene. Furthermore, our results evidenced that both methods detected the N gene more easily than the ORF gene. Taken together, these findings imply that the use of ddPCR, as an alternative to RT-qPCR, is necessary for the accurate diagnosis of hospitalized coronavirus disease 2019 patients.

New laboratory evidence for the association between endothelial dysfunction and COVID-19 disease progression.

There is growing evidence that angiotensin-converting enzyme 2 is highly expressed on endothelial cells, endothelial dysfunction plays a critical role in coronavirus disease 2019 (COVID-19) progression, but laboratory evidence is still lacking. This study established a multicenter retrospective cohort of 966 COVID-19 patients from three hospitals in Wuhan, China. We found that male (62.8% vs. 46.5%), old age [72 (17) vs. 60.5 (21)], and coexisting chronic diseases (88.5% vs. 60.0%) were associated with poor clinical prognosis in COVID-19. Furthermore, the deteriorated patients exhibited more severe multiorgan damage, coagulation dysfunction, and extensive inflammation. Additionally, a cross-sectional study including 41 non-COVID-19 controls and 39 COVID-19 patients assayed endothelial function parameters in plasma and showed that COVID-19 patients exhibited elevated vascular cell adhesion molecule-1 (VCAM-1) (median [IQR]: 0.32 [0.27] vs. 0.17 [0.11] µg/ml, p < 0.001), E-selectin (21.06 [12.60] vs. 11.01 [4.63] ng/ml, p < 0.001), tissue-type plasminogen activator (tPA) (0.22 [0.12] vs. 0.09 [0.04] ng/ml, p < 0.001), and decreased plasminogen activator inhibitor-1 (0.75 [1.31] vs 6.20 [5.34] ng/ml, p < 0.001), as compared to normal controls. Moreover, VCAM-1 was positively correlated with d-dimer (R = 0.544, p < 0.001); tPA was positively correlated with d-dimer (R = 0.800, p < 0.001) and blood urea nitrogen (R = 0.638, p < 0.001). Our findings further confirm the strong association between endothelial dysfunction and poor prognosis of COVID-19, which offers a rationale for targeting endothelial dysfunction as a therapeutic strategy for COVID-19.

Six-month follow-up of functional status in discharged patients with coronavirus disease 2019.

BACKGROUND: The long-term functional outcome of discharged patients with coronavirus disease 2019 (COVID-19) remains unresolved. We aimed to describe a 6-month follow-up of functional status of COVID-19 survivors. METHODS: We reviewed the data of COVID-19 patients who had been consecutively admitted to the Tumor Center of Union Hospital (Wuhan, China) between 15 February and 14 March 2020. We quantified a 6-month functional outcome reflecting symptoms and disability in COVID-19 survivors using a post-COVID-19 functional status scale ranging from 0 to 4 (PCFS). We examined the risk factors for the incomplete functional status defined as a PCFS > 0 at a 6-month follow-up after discharge. RESULTS: We included a total of 95 COVID-19 survivors with a median age of 62 (IQR 53-69) who had a complete functional status (PCFS grade 0) at baseline in this retrospective observational study. At 6-month follow-up, 67 (70.5%) patients had a complete functional outcome (grade 0), 9 (9.5%) had a negligible limited function (grade 1), 12 (12.6%) had a mild limited function (grade 2), 7 (7.4%) had moderate limited function (grade 3). Univariable logistic regression analysis showed a significant association between the onset symptoms of muscle or joint pain and an increased risk of incomplete function (unadjusted OR 4.06, 95% CI 1.33-12.37). This association remained after adjustment for age and admission delay (adjusted OR 3.39, 95% CI 1.06-10.81, p = 0.039). CONCLUSIONS: A small proportion of discharged COVID-19 patients may have an incomplete functional outcome at a 6-month follow-up; intervention strategies are required.

Correlation of Sexual Behavior Change, Family Function, and Male-Female Intimacy Among Adults Aged 18-44 Years During COVID-19 Epidemic.

INTRODUCTION: Coronavirus disease (COVID-19) has been declared a global pandemic. In this unprecedented situation, the intimate relationship, sexual behavior, and family functions of partners have also undergone unique changes. There are few reports on whether sexual behavior and family function affect intimate relationships between partners, especially among people aged 18 to 44 years. AIM: To analyze the influence of sociodemographic characteristics, family function, and changes in sexual behavior on male-female intimacy, the independent contributions of the aforementioned factors in this population group are required to be further investigated. METHODS: In the present study, 284 Chinese citizens aged 18-44 years completed the online questionnaire. The univariate analysis and cluster multiple linear regression were used to analyze the associations between sociodemographic factors, sexual-behavior changes, family function, and male-female intimacy. MAIN OUTCOME MEASURE: Family adaptation, partnership, growth, affection, resolve (APGAR) Scale and Relationship Assessment Scale were used to evaluate participants' family function and their intimacy. Details of the participants (sociodemographic and sexual factors) were obtained. RESULTS: The summary scores, with Relationship Assessment Scale and APGAR scales, were 27.19 ± 4.49 and 6.76 ± 2.28, respectively. About 43.3% of participants reported a decrease in sexual frequency. There were considerable differences among age, education level, sexual desire, sexual satisfaction, quality of sexual life, family function with male-female intimacy (P < .05). The sexual satisfaction and intimacy demonstrated a significant positive correlation (P < .05) by cluster multiple linear regression analysis. Compared with those who had a sexual life of mediocre quality, respondents who experienced a good quality sexual life had relatively higher scores in intimacy. The independent contributions of sociodemographic factors, sexual behavior factors, and family function in male-female intimacy were 13.0%, 38.2%, and 48.8%, respectively. CONCLUSIONS: Sexual behavior factors and family function were important independent determinants of partner intimacy among people aged 18-44 years. It can provide supportive information for health care to develop intervention plans and services to promote the harmonious development of intimate relationship. Feng Y-J, Fan Y-J, Su Z-Z, et al. Correlation of Sexual Behavior Change, Family Function, and Male-Female Intimacy Among Adults Aged 18-44 Years During COVID-19 Epidemic. Sex Med 2021;9:100301.

Impact of the COVID-19 pandemic on the epidemiology of out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has significantly influenced epidemiology, yet its impact on out-of-hospital cardiac arrest (OHCA) remains unclear. We aimed to evaluate the impact of the pandemic on the incidence and case fatality rate (CFR) of OHCA. We also evaluated the impact on intermediate outcomes and clinical characteristics. METHODS: PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases were searched from inception to May 3, 2021. Studies were included if they compared OHCA processes and outcomes between the pandemic and historical control time periods. Meta-analyses were performed for primary outcomes [annual incidence, mortality, and case fatality rate (CFR)], secondary outcomes [field termination of resuscitation (TOR), return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge], and clinical characteristics (shockable rhythm and etiologies). This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021253879). RESULTS: The COVID-19 pandemic was associated with a 39.5% increase in pooled annual OHCA incidence (p < 0.001). Pooled CFR was increased by 2.65% (p < 0.001), with a pooled odds ratio (OR) of 1.95 for mortality [95% confidence interval (95%CI) 1.51-2.51]. There was increased field TOR (OR = 2.46, 95%CI 1.62-3.74). There were decreased ROSC (OR = 0.65, 95%CI 0.55-0.77), survival to hospital admission (OR = 0.65, 95%CI 0.48-0.89), and survival to discharge (OR = 0.52, 95%CI 0.40-0.69). There was decreased shockable rhythm (OR = 0.73, 95%CI 0.60-0.88) and increased asphyxial etiology of OHCA (OR = 1.17, 95%CI 1.02-1.33). CONCLUSION: Compared to the pre-pandemic period, the COVID-19 pandemic period was significantly associated with increased OHCA incidence and worse outcomes.

Optimal Internet of Things Technology Adoption Decisions and Pricing Strategies for High-Traceability Logistics Services

The Internet of Things (IoT) technology-based tracking system can reduce freight loss/damage during delivery, thereby avoiding wasting social resources. In this study, we address the issue of whether an E-retailer with a logistics arm should provide high-traceability logistics value-added service (based on IoT technology) in two customer segments and analyze their pricing decision. We found that companies always adopt IoT when equipment operation cost is low and not when the cost is high. Otherwise, the optimal IoT adoption strategy for a company depends on multiple factors, for example, the internal operation efficiency of a company. Providing high-traceability service as one kind of public service does not necessarily optimize social welfare even if the overall delivery failure is reduced. The customers’ preference for traceability significantly affects the company’s decision. Hence, we suggest that the company should implement a comprehensive investigation before launching a specific strategy.

Does pre-existent physical inactivity have a role in the severity of COVID-19?

BACKGROUND AND AIMS: Physical inactivity is considered an important lifestyle factor for overweight and cardiovascular disease. We aimed to investigate the association between pre-existent physical inactivity and the risk of severe coronavirus disease 2019 (COVID-19). METHODS: We included 164 (61.8 ± 13.6 years) patients with COVID-19 who were admitted between 15 February and 14 March 2020 in this retrospective study. We evaluated the association between pre-existent physical inactivity and severe COVID-19 using a logistic regression model. RESULTS: Of 164 eligible patients with COVID-19, 103 (62.8%) were reported to be physically inactive. Univariable logistic regression analysis showed that physical inactivity was associated with an increased risk of severe COVID-19 [unadjusted odds ratio (OR) 6.53, 95% confidence interval (CI) 1.88-22.62]. In the multivariable regression analysis, physical inactivity remained significantly associated with an increased risk of severe COVID-19 (adjusted OR 4.12, 95% CI 1.12-15.14) after adjustment for age, sex, stroke, and overweight. CONCLUSION: Our data showed that pre-existent physical inactivity was associated with an increased risk of experiencing severe COVID-19. Our findings indicate that people should be encouraged to keep physically active to be at a lower risk of experiencing a severe illness when COVID-19 infection seems unpredicted.The reviews of this paper are available via the supplemental material section.

Artificial Intelligence Applications for COVID-19 in Intensive Care and Emergency Settings: A Systematic Review.

Background: Little is known about the role of artificial intelligence (AI) as a decisive technology in the clinical management of COVID-19 patients. We aimed to systematically review and critically appraise the current evidence on AI applications for COVID-19 in intensive care and emergency settings. Methods: We systematically searched PubMed, Embase, Scopus, CINAHL, IEEE Xplore, and ACM Digital Library databases from inception to 1 October 2020, without language restrictions. We included peer-reviewed original studies that applied AI for COVID-19 patients, healthcare workers, or health systems in intensive care, emergency, or prehospital settings. We assessed predictive modelling studies and critically appraised the methodology and key findings of all other studies. Results: Of fourteen eligible studies, eleven developed prognostic or diagnostic AI predictive models, all of which were assessed to be at high risk of bias. Common pitfalls included inadequate sample sizes, poor handling of missing data, failure to account for censored participants, and weak validation of models. Conclusions: Current AI applications for COVID-19 are not ready for deployment in acute care settings, given their limited scope and poor quality. Our findings underscore the need for improvements to facilitate safe and effective clinical adoption of AI applications, for and beyond the COVID-19 pandemic.

Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies.

Neutralizing monoclonal antibodies (nAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represent promising candidates for clinical intervention against coronavirus disease 2019 (COVID-19). We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain (RBD) of the viral spike (S) protein and the receptor angiotensin converting enzyme 2 (ACE2). However, the structural basis for their potent neutralizing activity remains unclear. Here, we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2. The bivalent binding of the full-length IgG is found to associate with more RBDs in the "up" conformation than the monovalent binding of Fab, perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein. Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities. This work provides a structural basis for further understanding the mechanism of nAbs, especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit.