Low-Cost Systematic Methodology for Rapidly Constructing a Physiological Monitoring Interface in ICU

During the COVID-19 pandemic, which emerged in 2020, many patients were treated in isolation wards because of the high infectivity and long incubation period of COVID-19. Therefore, monitoring systems have become critical to patient care and to safeguard medical professional safety. The user interface is very important to the surveillance system;therefore, we used web technology to develop a system that can create an interface based on user needs. When the surveillance scene needs to be changed, the surveillance location can be changed at any time, effectively reducing the costs and time required, so that patients can achieve timely and appropriate goals of treatment. ZigBee was employed to develop a monitoring system for intensive care units (ICUs). Unlike conventional GUIs, the proposed GUI enables the monitoring of various aspects of a patient, and the monitoring interface can be modified according to the user needs. A simulated ICU environment monitoring system was designed to test the effectiveness of the system. The simulated environment and monitoring nodes were set up at positions consistent with the actual clinical environments to measure the time required to switch between the monitoring scenes or targets on the GUI. A novel system that can construct ZigBee-simulated graphical monitoring interfaces on demand was proposed in this study. The locations of the ZigBee monitoring nodes in the user interface can be changed at any time. The time required to deploy the monitoring system developed in this study was 4 min on average, which is much shorter than the time required for conventional methods (131 min). The system can effectively overcome the limitations of the conventional design methods for monitoring interfaces. This system can be used to simultaneously monitor the basic physiological data of numerous patients, enabling nursing professionals to instantly determine patient status and provide appropriate treatments. The proposed monitoring system can be applied to remote medical care after official adoption.

HLA-Bw4 in association with KIR3DL1 favors natural killer cell-mediated protection against severe COVID-19.

Replicating SARS-CoV-2 has been shown to degrade HLA class I on target cells to evade the cytotoxic T-cell (CTL) response. HLA-I downregulation can be sensed by NK cells to unleash killer cell immunoglobulin-like receptor (KIR)-mediated self-inhibition by the cognate HLA-I ligands. Here, we investigated the impact of HLA and KIR genotypes and HLA-KIR combinations on COVID-19 outcome. We found that the peptide affinities of HLA alleles were not correlated with COVID-19 severity. The predicted poor binders for SARS-CoV-2 peptides belong to HLA-B subtypes that encode KIR ligands, including Bw4 and C1 (introduced by B*46:01), which have a small F pocket and cannot accommodate SARS-CoV-2 CTL epitopes. However, HLA-Bw4 weak binders were beneficial for COVID-19 outcome, and individuals lacking the HLA-Bw4 motif were at higher risk for serious illness from COVID-19. The presence of the HLA-Bw4 and KIR3DL1 combination had a 58.8% lower risk of developing severe COVID-19 (OR = 0.412, 95% CI = 0.187-0.904, p = 0.02). This suggests that HLA-Bw4 alleles that impair their ability to load SARS-CoV-2 peptides will become targets for NK-mediated destruction. Thus, we proposed that the synergistic responsiveness of CTLs and NK cells can efficiently control SARS-CoV-2 infection and replication, and NK-cell-mediated anti-SARS-CoV-2 immune responses being mostly involved in severe infection when the level of ORF8 is high enough to degrade HLA-I. The HLA-Bw4/KIR3DL1 genotype may be particularly important for East Asians undergoing COVID-19 who are enriched in HLA-Bw4-inhibitory KIR interactions and carry a high frequency of HLA-Bw4 alleles that bind poorly to coronavirus peptides.

Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target.

In addition to the anti-infection response, neutrophils are linked to tumor progression through the secretion of inflammation components and neutrophil extracellular traps (NETs) formation. NET is a web-like structure constituted by a chromatin scaffold coated with specific nuclear and cytoplasmic proteins, such as histone and granule peptides. Increasing evidence has demonstrated that NETs are favorable factors to promote tumor growth, invasion, migration, and immunosuppression. However, the cell-cell interaction between NETs and other cells (tumor cells and immune cells) is complicated and poorly studied. This work is the first review to focus on the intercellular communication mediated by NETs in cancer. We summarized the complex cell-cell interaction between NETs and other cells in the tumor microenvironment. We also address the significance of NETs as both prognostic/predictive biomarkers and molecular targets for cancer therapy. Moreover, we presented a comprehensive landscape of cancer immunity, improving the therapeutic efficacy for advanced cancer in the future.

Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era (preprint)

Background: Oral nirmatrelvir/ritonavir is a treatment for COVID-19, but whether treatment during the acute phase reduces the risk of developing Long COVID is unknown. Methods: Using the Covid Citizen Science (CCS) online cohort, we surveyed individuals who reported their first SARS-CoV-2 positive test between March and August 2022 regarding Long COVID symptoms. We excluded those who were pregnant, unvaccinated, hospitalized for COVID-19, or received other antiviral therapy. The primary exposure was oral nirmatrelvir/ritonavir. The primary outcome was the presence of any Long COVID symptoms reported on cross-sectional surveys in November and December 2022. We used propensity-score models and inverse probability of treatment weighting to adjust for differences in treatment propensity. Our secondary question was whether symptom or test positivity rebound were associated with Long COVID. Results: 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the survey. Median age was 55 years and 66% were female. We did not identify an association between nirmatrelvir/ritonavir treatment and Long COVID symptoms (OR 1.15; 95%CI 0.80-1.64). Among n=666 treated with nirmatrelvir/ritonavir who responded who responded to questions about rebound, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR 1.34; 95%CI 0.74-2.41; p=0.33). Conclusions: Within this cohort, treatment with nirmatrelvir/ritonavir among vaccinated, non-hospitalized individuals was not associated with lower prevalence of Long COVID symptoms or severity of Long COVID. Experiencing rebound symptoms or test positivity is not strongly associated with developing Long COVID.

Factors Associated with Long Covid Symptoms in an Online Cohort Study (preprint)

Importance: Prolonged symptoms following SARS-CoV-2 infection, or Long COVID, is common, but few prospective studies of Long COVID risk factors have been conducted. Objective: To determine whether sociodemographic factors, lifestyle, or medical history preceding COVID-19 or characteristics of acute SARS-CoV-2 infection are associated with Long COVID. Design: Cohort study with longitudinal assessment of symptoms before, during, and after SARS-CoV-2 infection, and cross-sectional assessment of Long COVID symptoms using data from the COVID-19 Citizen Science (CCS) study. Setting: CCS is an online cohort study that began enrolling March 26, 2020. We included data collected between March 26, 2020, and May 18, 2022. Participants: Adult CCS participants who reported a positive SARS-CoV-2 test result (PCR, Antigen, or Antibody) more than 30 days prior to May 4, 2022, were surveyed. Exposures: Age, sex, race/ethnicity, education, employment, socioeconomic status/financial insecurity, self-reported medical history, vaccination status, time of infection (variant wave), number of acute symptoms, pre-COVID depression, anxiety, alcohol and drug use, sleep, exercise. Main Outcome: Presence of at least 1 Long COVID symptom greater than 1 month after acute infection. Sensitivity analyses were performed considering only symptoms beyond 3 months and only severe symptoms. Results: 13,305 participants reported a SARS-CoV-2 positive test more than 30 days prior, 1480 (11.1% of eligible) responded to a survey about Long COVID symptoms, and 476 (32.2% of respondents) reported Long COVID symptoms (median 360 days after infection). Respondents' mean age was 53 and 1017 (69%) were female. Common Long COVID symptoms included fatigue, reported by 230/476 (48.3%), shortness of breath (109, 22.9%), confusion/brain fog (108, 22.7%), headache (103, 21.6%), and altered taste or smell (98, 20.6%). In multivariable models, number of acute COVID-19 symptoms (OR 1.30 per symptom, 95%CI 1.20-1.40), lower socioeconomic status/financial insecurity (OR 1.62, 95%CI 1.02-2.63), pre-infection depression (OR 1.08, 95%CI 1.01-1.16), and earlier variants (OR 0.37 for Omicron compared to ancestral strain, 95%CI 0.15-0.90) were associated with Long COVID symptoms. Conclusions and Relevance: Variant wave, severity of acute infection, lower socioeconomic status and pre-existing depression are associated with Long COVID symptoms.

Benefit from a high store visiting cost in an omnichannel with BOPS.

Omnichannel sales surge in the coronavirus pandemic. This paper establishes an analytical model to study when a firm can benefit from implementing the omnichannel strategy of buy-online and pick-up in-store (BOPS), where the market characteristics are captured by the two-dimensional heterogeneity of product valuation and online waiting cost. The increase in the store visiting cost will reduce BOPS consumers' willingness to pay, but it will also strengthen the encroachment of BOPS on traditional dual-channel. The results show that the firm can benefit from the BOPS strategy when the store visiting cost is relatively high. This well explains the rapid development of the omnichannel with BOPS because of a high store visiting cost during COVID-19. Furthermore, sharply contrasting to the traditional dual-channel sales in which a higher store visiting cost always hurts the firm, the profit under BOPS can be nonmonotonic in the store visiting cost and the firm can benefit from a higher store visiting cost. Specifically, the combination of cross-selling effect, BOPS encroachment effect and BOPS expansion reduction effect associated with the store visiting cost can result in a U-shaped or inverse U-shaped BOPS profit. In addition, introducing BOPS motivates the firm to either increase or decrease the optimal price, conditional on the store visiting cost. For consumers, online and offline consumers can also indirectly benefit from the BOPS strategy, though they may not enjoy the BOPS service.

Emergence and Persistent Dominance of Omicron BA.2.3.7 Variant in Community Outbreaks in Taiwan (preprint)

Using high-throughput sequencing of the SARS-CoV-2 genome, we have analyzed 2405 PCR-positive swab samples from 2339 individuals and identified the Omicron BA.2.3.7 variant as a major lineage of the recent community outbreak in Taiwan. Since April 2022, a series of new waves of Omicron cases have surfaced in Taiwan and spread throughout the island. We conducted genomic surveillance with a high success rate and have submitted 1966 full-length Omicron sequences to GISAID. This has permitted identification of signature amino acid changes (ORF1a:L631F, S:K97E, N:M322I) in 1584 (80.6%) of the translated SARS-CoV-2 sequences. The newly established BA.2.3.7 lineage, which is relatively common in Asian countries, is now persistently present in Taiwan. By June 2022 this dominant strain had established a substantial existence in the sequence pool, resulting in additional mutations. The rapid spread and expansion of the Omicron BA.2.3.7 lineage in Asia has had an important socioeconomic impact on health policy.

Data driven time-varying SEIR-LSTM/GRU algorithms to track the spread of COVID-19.

COVID-19 is an infectious disease caused by a newly discovered coronavirus, which has become a worldwide pandemic greatly impacting our daily life and work. A large number of mathematical models, including the susceptible-exposed-infected-removed (SEIR) model and deep learning methods, such as long-short-term-memory (LSTM) and gated recurrent units (GRU)-based methods, have been employed for the analysis and prediction of the COVID-19 outbreak. This paper describes a SEIR-LSTM/GRU algorithm with time-varying parameters that can predict the number of active cases and removed cases in the US. Time-varying reproductive numbers that can illustrate the progress of the epidemic are also produced via this process. The investigation is based on the active cases and total cases data for the USA, as collected from the website "Worldometer". The root mean square error, mean absolute percentage error and r2 score were utilized to assess the model's accuracy.

A Low-Cost Physiological Monitoring Interface for Intensive Care Unit (preprint)

Background: During the COVID-19 pandemic, which emerged in 2020, many patients were treated in isolation wards because of the high infectivity and long incubation period of COVID-19. Therefore, monitoring systems have become critical to patient care and to safeguard medical professional safety.Objective: The user interface is very important to the surveillance system; therefore, we use web technology to develop a system that can create an interface based on user needs. When the surveillance scene needs to be changed, the surveillance location can be changed at any time, effectively reducing costs and time required, so that patients can achieve timely and appropriate goals of treatment.Methods: ZigBee was employed to develop a monitoring system for intensive care units (ICUs). Unlike conventional GUIs, the proposed GUI enables monitoring of various aspects of a patient, and the monitoring interface can be modified according to user needs. A simulated ICU environment monitoring system is designed to test the effectiveness of the system. The simulated environment and monitoring nodes were set up at positions consistent with the actual clinical environments to measure the time required to switch between monitoring scenes or targets on the GUI.Results: A low-cost system that can construct ZigBee-simulated graphical monitoring interfaces on demand was proposed in this study. The system can effectively overcome the limitations of conventional design methods for monitoring interfaces.Conclusion: This system can be used to simultaneously monitor the basic physiological data of numerous patients, enabling nursing professionals to instantly determine patient status and provide appropriate treatments. The proposed monitoring system can be applied to remote medical care after official adoption.

Transparent Polyurethane Coating with Synergistically Enhanced Antibacterial Mechanism Composed of Low Surface Free Energy and Biocide

Recently, antibacterial coatings have gained great attention after the outbreak of COVID-19, thus durable transparent polyurethane (PU) coatings with anti-bacterial and anti-fingerprint performances are highly desired. In this work, the low surface free energy enables the hydroxyl-terminated polysiloxanes modified with quaternary ammonium salts (PQMS) enriched on the surface. The optimal PU-PQMS-40% coating with the thickness of 15 μm displayed 96% light transmittance and can be adopted to diverse substrates. This resultant coating exhibits excellent antibacterial activity against Gram-negative E. coli (99.2%) and Gram-positive S. aureus (98.6%) because of the synergistically enhanced antibacterial mechanism of both low surface free energy (27.54 ± 0.75 mJ·m−2) and quaternary ammonium salts (QAs). It is noteworthy that this antibacterial PU coating is capable of retaining its properties even after being subjected to 210 cycles of abrasion tests, manifesting a superior self-renewability. This coating system with combined features of transparency, antibacterial performance, chemical resistance, and durability make it a promising candidate for applications in the fields of electronic devices, automobile interiors, intelligent glass, and marine antifouling.

Toward green transition in the post Paris Agreement era: The case of Taiwan

The Paris Agreement opens a new era to combat the global climate change. Apart from this, the COVID-19 provides an opportunity of restructuring industries of an economy. The current literature and policy practices have addressed the need for including green transition measures in the adaptation and recovery plans to avoid a significant rebound effect on the environment. Given the fact that emission mitigation and the pandemic might have asymmetric impacts on the industrial structure, this study makes a quantitative contribution in analyzing the economy-wide impacts of main green transition policies to elucidate the significance of renewable energy development and market-based instruments for Taiwan. Our results show that offshore wind alone would not be sufficient to re-direct the energy-intensive pathway for Taiwan. In this regard, a sound green policy transition package ought to complement with a market-based instruments (such as carbon tax) and suitable tax revenue recycling scheme in order to reach a ‘win-win situation’ of a reduction of GHG emissions and a better economic performance.

SEIR model with unreported infected population and dynamic parameters for the spread of COVID-19.

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be transmitted through human interaction. In this paper, we present a Piecewise Susceptible-Exposed-Infectious-Unreported-Removed model for infectious diseases and discuss qualitatively and quantitatively. The parameters are explored by mathematical and statistical methods. Numerical simulations of these models are performed on COVID-19 US data and Python is used in the visualization of results. Outbreak factor is generated by piecewise model to explore the future trend of the US pandemic. Several error metrics are given to discuss the accuracy of the models. The main achievement of this paper is to propose the piecewise model and find the relationship between spread of pandemic and mitigation measures to control it by observing the results of numerical simulations. Performance analysis of piecewise model is presented based on COVID-19 data obtained by 'worldmeter'.

An Immunobridging study to evaluate the neutralizing antibody titer in adults immunized with two doses of either ChAdOx1-nCov-19 (AstraZeneca) or MVC-COV1901. (preprint)

Background Rapid development and deployment of vaccine is crucial to control the continuously evolving COVID-19 pandemic. Placebo-controlled phase 3 efficacy trial is still standard for authorizing vaccines in majority of the world. However, due to lack of cases or participants in parts of the world, this has not always been feasible. An alternative to efficacy trial is immunobridging, in which the immune response or correlates of protection of a vaccine candidate is compared against an approved vaccine. Here we describe a case study where our candidate vaccine, MVC-COV1901, has been granted for emergency use authorization (EUA) locally based on the non-inferiority immunobridging process. Methods The per protocol immunogenicity (PPI) subset from the MVC-COV1901 phase 2 trial was used for this study and consisted of 903 subjects who have received two doses of MVC-COV1901 as scheduled in the clinical trial. The comparator set of population consisted of 200 subjects of [≥] 20 years of age who were generally healthy, and have received two doses of AstraZeneca ChAdOx nCOV-19 (AZD1222) recruited from Taoyuan General Hospital, Ministry of Health and Welfare. Results MVC-COV1901 was shown to have a geometric mean titer (GMT) ratio lower bound 95% confidence internal (CI) of 3.4 against the comparator vaccine and a seroconversion rate of 95.5% at the 95% CI lower bound, which both exceeded the criteria set by the Taiwan regulatory authority for EUA approval. These results supported the EUA approval of MVC-COV1901 by the Taiwanese regulatory authority in July 2021. Following the consensus of the International Coalition of Medicines Regulatory Authorities (ICMRA), countries from the Access Consortium has recently adopted the use of immunobridging studies as acceptable for authorizing COVID-19 vaccines in lieu of efficacy data. Conclusion The data presented in the study showed that it is reasonably likely that the vaccine efficacy of MVC-COV1901 is similar or superior to that of AZ. Data could be used in support of further vaccine development and regulatory approval.

Prevalence of Dry Eye Disease Among Chinese High School Students During the COVID-19 Outbreak (preprint)

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.

A Low-Producing Haplotype of Interleukin-6 Disrupting CTCF Binding Is Protective against Severe COVID-19.

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.

Potent Anti-Delta Effect By a Booster Third-Dose of UB-612, a Precision-Designed SARS-CoV-2 Multitope Protein-Peptide Vaccine (preprint)

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

COVID-19-related post-traumatic growth in the general public: a cross-sectional study from Yunnan, China.

To investigate post-traumatic growth induced by COVID-19 pandemic in certain Yunnan residents and to analyze its influencing factors. A total of 581 permanent residents of Yunnan province completed the electronic questionnaire from 18 April 2020 to 26 April 2020. Logistic regression analysis showed that the educational levels, self-perceived health status, family history of infectious diseases, family history of infectious diseases, personality and frequency of going through COVID-19 related news were influencing factors of PTG (P < 0.05). As a traumatic event, the threat of COVID-19 may enable some people to gain positive psychological development in adversity. This will provide reference for public psychological crisis intervention following the COVID-19 pandemic.

Characteristics of COVID-19-related Clinical Studies and Factors Affecting the Recruitment and Completeness: a Large Cross-sectional Study (preprint)

Background: Coronavirus disease 2019 (COVID-19) has generated an unprecedented clinical research response, but the data about the characteristics of COVID-19-related clinical studies were scarce. The study aimed to describe the characteristics of COVID-19-related clinical studies registered at ClinicalTrials.gov and further identify factors affecting the recruitment and completeness of these studies. Methods: : The study extracted 5,672 studies and included 5,430 studies relating to COVID-19 registered at ClinicalTrials.gov. We presented the characteristics of all included clinical studies. Identification of risk factors for recruitment status was achieved using the multiple logistic regression models, and identification of risk factors for completion time was obtained using the multiple Cox proportional hazards regression models. Subgroup analyses were also performed in the interventional studies. Results: : Of the included studies, only 19.59% (1064/5430) had completed recruitment, and 55.93% (3037/5430) were interventional studies. The peak of the number of clinical studies relating to COVID-19 was seven months earlier than the first peak of the number of COVID-19 cases globally. In all included studies, participants only including male (P=0.02), Participants including child (P=0.01), smaller enrollment (P<0.01), and studies not being funded by industry (P=0.01) and the National Institutes of Health (NIH) (P<0.01), and observational studies (P<0.01) tended to be associated to higher completed recruitment rates. Regarding the interventional studies, Participants including child (P=0.04), smaller enrollment (P<0.01), a crossover intervention model (P<0.01), and primary purpose involving in device feasibility (P<0.01) and treatment (P=0.03) were associated with shorter completion time, while being funded by industry (P=0.01) and NIH (P<0.01), primary purpose involving in basic science (P<0.01), and biological interventions (P<0.01) were associated with longer completion time. Conclusion: A multitude of clinical studies relating to COVID-19 are registered in responding to the pandemic and the response is rapid and timely, but these clinical studies are frequently not completed. Increased focus on establishing global initiatives and networks to coordinate recruitment efforts may be needed. Several independent risk factors are identified to guide the design of COVID-19-related clinical studies. This may be significant to avoid waste and ensure that the participation of all participants in clinical researches contributes to the treatment or prevention of COVID-19.

Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor (preprint)

Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.

Psychometric Validation of the Persian Version of the COVID-19-Related Psychological Distress Scale and Association with COVID-19 Fear, COVID-19 Anxiety, Optimism, and Lack of Resilience.

The outbreak of the coronavirus disease-2019 (COVID-19) has resulted in a global health crisis. The COVID-19 pandemic has caused psychological distress, both in infected and uninfected individuals. The present study evaluated the validity and factor structure of the COVID-19-Related Psychological Distress Scale (CORPDS) among the general public of the Persian-speaking population. The original version of the CORPDS was translated and back-translated into Persian, followed by a pilot study. A total sample (n = 623) completed an online survey including the CORPDS, Fear of COVID-19 Scale (FCV-19S), Coronavirus Anxiety Scale (CAS), Kessler Psychological Distress Scale (K10), Life Orientation Test-Revised (LOT-R), and Brief Resilience Scale (BRS). The Persian CORPDS had very good internal consistency and moderate test-retest reliability after 4 weeks. Maximum likelihood confirmatory factor analysis (CFA) was conducted to test construct validity (χ2/df = 2.39, CFI = 0.95, SRMR = 0.046, PCLOSE = 0.67 > 0.05, RMSEA = 0.047, 90% CI [0.038, 0.056]). Measurement invariance was performed across gender, including configural invariance, metric invariance, scalar invariance, and error variance invariance, and yielded further support for the two-factor structure of the CORPDS. The CORPDS correlated with the score on the K10 (r = 0.46, p < 0.01, 95% CI [0.43, 0.48]), CAS (r = 0.43, p < 0.01, 95% CI [0.37, 0.45]), FCV-19S (r = 0.29, p < 0.01, 95% CI [0.27, 0.32]), LOT-R (r = - 0.19, p < 0.01, 95% CI [- 0.15, - 0.24]) and BRS (r = - 0.56, p < 0.01, 95% CI [- 0.50, - 0.61]). Resilience was associated with lower psychological distress (ß = - 0.54, SE = 0.05, p < 0.001). The findings provide evidence that CORPDS is a reliable and valid instrument for assessing psychological distress generated by COVID-19 among a healthy Persian-speaking population.