[Component identification and analysis in vivo of Sanhan Huashi formula].

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging.

Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits-healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health-in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near HTT and MAML3 using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.

A comparative study on the three calculation methods for reproduction numbers of COVID-19

Objective This study uses four COVID-19 outbreaks as examples to calculate and compare merits and demerits, as well as applicational scenarios, of three methods for calculating reproduction numbers. Method The epidemiological characteristics of the COVID-19 outbreaks are described. Through the definition method, the next-generation matrix-based method, and the epidemic curve and serial interval (SI)-based method, corresponding reproduction numbers were obtained and compared. Results Reproduction numbers (Reff), obtained by the definition method of the four regions, are 1.20, 1.14, 1.66, and 1.12. Through the next generation matrix method, in region H Reff = 4.30, 0.44;region P Reff = 6.5, 1.39, 0;region X Reff = 6.82, 1.39, 0;and region Z Reff = 2.99, 0.65. Time-varying reproduction numbers (Rt), which are attained by SI of onset dates, are decreasing with time. Region H reached its highest Rt = 2.8 on July 29 and decreased to Rt < 1 after August 4;region P reached its highest Rt = 5.8 on September 9 and dropped to Rt < 1 by September 14;region X had a fluctuation in the Rt and Rt < 1 after September 22;Rt in region Z reached a maximum of 1.8 on September 15 and decreased continuously to Rt < 1 on September 19. Conclusion The reproduction number obtained by the definition method is optimal in the early stage of epidemics with a small number of cases that have clear transmission chains to predict the trend of epidemics accurately. The effective reproduction number Reff, calculated by the next generation matrix, could assess the scale of the epidemic and be used to evaluate the effectiveness of prevention and control measures used in epidemics with a large number of cases. Time-varying reproduction number Rt, obtained via epidemic curve and SI, can give a clear picture of the change in transmissibility over time, but the conditions of use are more rigorous, requiring a greater sample size and clear transmission chains to perform the calculation. The rational use of the three methods for reproduction numbers plays a role in the further study of the transmissibility of COVID-19.

Effects of phenylpyridinone derivative on the replication of Porcine Deltacoronavirus

The purpose of this study was to investigate the antiviral effect of phenylpyridinone derivative JIB-04 on porcine deltacoronavirus (PDCoV), and explore the possible mechanism. Cell viability after treatment with different concentrations of JIB-04 was detected by CCK-8, and the 50% cytotoxic concentration (CC50) and 50% effective concentration (EC50) were calculated. TCID50 method was used to detect the effects of JIB-04 pretreatment and co-treatment on PDCoV replicationand the effect of JIB-04 treatment on virus attachment and penetration. Finally, qRT-PCR, TCID50 and Western blot methods were used to detect the effect of JIB-04 on virus replication at different times post infection. The results showed that JIB-04 did not affect the cell viability of LLC-PK cells at all tested concentrations, and CC50>640 micro mol.L-1, EC50=0.216 micro mol.L-1, and SI index is greater than 2 963. Compared with untreated virus infection group, JIB-04 treatment significantly reduced the virus titer (P < 0.001), but it had no effect on attachment or penetration of PDCoV. At 6 h post infection, compared with untreated virus infection group, virus titer in JIB-04 treatment group was significantly decreased (P < 0.01). At 12 and 24 h post infection, virus titer, genome copy number, and N protein expression level all significantly decreased (P < 0.01). JIB-04 has a low cytotoxicity and a high selective index, and can protect against PDCoV infection in vitro, making it a potential antiviral drug. JIB-04 can inhibit synthesis of viral RNA, protein and PDCoV replication.

Comparison of epidemiological characteristics and transmissibility of different strains of COVID-19 based on the incidence data of all local outbreaks in China as of March 1, 2022

Background The epidemiological characteristics and transmissibility of Coronavirus Disease 2019 (COVID-19) may undergo changes due to the mutation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) strains. The purpose of this study is to compare the differences in the outbreaks of the different strains with regards to aspects such as epidemiological characteristics, transmissibility, and difficulties in prevention and control. Methods COVID-19 data from outbreaks of pre-Delta strains, the Delta variant and Omicron variant, were obtained from the Chinese Center for Disease Control and Prevention (CDC). Case data were collected from China's direct-reporting system, and the data concerning outbreaks were collected by on-site epidemiological investigators and collated by the authors of this paper. Indicators such as the effective reproduction number (Reff), time-dependent reproduction number (Rt), rate of decrease in transmissibility (RDT), and duration from the illness onset date to the diagnosed date (DID)/reported date (DIR) were used to compare differences in transmissibility between pre-Delta strains, Delta variants and Omicron variants. Non-parametric tests (namely the Kruskal-Wallis H and Mean-Whitney U tests) were used to compare differences in epidemiological characteristics and transmissibility between outbreaks of different strains. P < 0.05 indicated that the difference was statistically significant. Results Mainland China has maintained a “dynamic zero-out strategy” since the first case was reported, and clusters of outbreaks have occurred intermittently. The strains causing outbreaks in mainland China have gone through three stages: the outbreak of pre-Delta strains, the outbreak of the Delta variant, and outbreaks involving the superposition of Delta and Omicron variant strains. Each outbreak of pre-Delta strains went through two stages: a rising stage and a falling stage, Each outbreak of the Delta variant and Omicron variant went through three stages: a rising stage, a platform stage and a falling stage. The maximum Reff value of Omicron variant outbreaks was highest (median: 6.7;ranged from 5.3 to 8.0) and the differences were statistically significant. The RDT value of outbreaks involving pre-Delta strains was smallest (median: 91.4%;[IQR]: 87.30–94.27%), and the differences were statistically significant. The DID and DIR for all strains was mostly in a range of 0–2 days, with more than 75%. The range of duration for outbreaks of pre-Delta strains was the largest (median: 20 days, ranging from 1 to 61 days), and the differences were statistically significant. Conclusion With the evolution of the virus, the transmissibility of the variants has increased. The transmissibility of the Omicron variant is higher than that of both the pre-Delta strains and the Delta variant, and is more difficult to suppress. These findings provide us with get a more clear and precise picture of the transmissibility of the different variants in the real world, in accordance with the findings of previous studies. Reff is more suitable than Rt for assessing the transmissibility of the disease during an epidemic outbreak.

Therapeutic prospects of ceRNAs in COVID-19

Since the end of 2019, COVID-19 caused by SARS-CoV-2 has spread worldwide, and the understanding of the new coronavirus is in a preliminary stage. Currently, immunotherapy, cell therapy, antiviral therapy, and Chinese herbal medicine have been applied in the clinical treatment of the new coronavirus;however, more efficient and safe drugs to control the progress of the new coronavirus are needed. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) may provide new therapeutic targets for novel coronavirus treatments. The first aim of this paper is to review research progress on COVID-19 in the respiratory, immune, digestive, circulatory, urinary, reproductive, and nervous systems. The second aim is to review the body systems and potential therapeutic targets of lncRNAs, miRNAs, and circRNAs in patients with COVID-19. The current research on competing endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA) in SARS-CoV-2 is summarized. Finally, we predict the possible therapeutic targets of four lncRNAs, MALAT1, NEAT1, TUG1, and GAS5, in COVID-19. Importantly, the role of PTEN gene in the ceRNA network predicted by lncRNA MALAT1 and lncRNA TUG1 may help in the discovery and clinical treatment of effective drugs for COVID-19.

Investigation of a family cluster outbreak of coronavirus disease 2019 in Xi-an. (Special Issue: Spatio-temporal dynamics analysis, risk assessment and emergency management for COVID-19 epidemic.) [Chinese]

Objective: To investigate the transmission characteristics of a family cluster outbreak of coronavirus disease 2019 (COVID-19) in Xi-an, in order to provide reference for prevention and control efforts.

Study of the temperature sensitivity of severe fever with thrombocytopenia syndrome virus

This study investigated the temperature sensitivity of severe fever with thrombocytopenia syndrome virus (SFTSV) to provide a basis for SFTSV disinfection and laboratory biosafety protection. We divided SFTSV cell culture supernatants into 250 L PCR vials at 100 L/tube, and placed them in a refrigerator at 4..C, and a metal bath at 25..C, 37..C, 39..C, 56..C, and 70..C. After treatment for predetermined periods of time, the viral titer was determined through indirect immunofluorescence in Vero cells. With increasing temperature, the rate of decline of the viral titer increased. After incubation at 4..C, 25..C, 37..C, and 39..C for 24 h, the titers decreased from 107.25/100 L to 107.00/100 L, 106.75/100 L, 106.50/100 L, and 105.00/100 L, respectively. At the same temperature, with prolonged storage time, the decrease in titer became more pronounced. After SFTSV was placed at 4..C, 25..C, 37..C for 72 h, the viral titer decreased from 107.25/100 L to 106.63/100 L, 106.50/100 L, and 103.38/100 L, respectively. SFTSV lost its infectivity after incubation at 39..C for 72 h. SFTSV was inactivated after exposure to 56..C for 180 min or 70..C for 5 min. We concluded that SFTSV is inactivated after incubation at 70..C for 5 min. However, after 3 days of exposure to 4..C and 25..C, the viral titer did not change significantly. Laboratories and medical staff should focus on personal protection and disinfection of items contaminated by SFTSV.

Genetic Landscape of the ACE2 Coronavirus Receptor.

BACKGROUND: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood. METHODS: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data. RESULTS: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells. CONCLUSIONS: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.

Prevention and Control of Nosocomial Infections among Hospital Logistic Staff During the COVID-19 Pandemic.

Hospital logistics staff comprise a crucial, albeit easily overlooked, group in the prevention and control of hospital nosocomial infections, especially during the COVID-19 pandemic. From the perspective of hospital safety improvement, this paper describes the current situation and challenges in the prevention and control of nosocomial infections among hospital logistics staff. We also provide the following suggestions to improve nosocomial infections: (1) updating the learning system of nosocomial infections, (2) reinforcing the training of infections prevention, (3) properly arranging manpower and resources, and (4) improving the supervision and management system.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

Respiratory care for the critical patients with 2019 novel coronavirus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through respiratory droplets, aerosols and close contact. Cross infections occur because viruses spread rapidly among humans. Nineteen percent (19%) of the infected patients developed severe pneumonia and acute respiratory distress syndrome (ARDS). Hypoxemia usually occurs and patients may require oxygen therapy or mechanical ventilation (MV) support. In this article, recently published clinical experience and observational studies were reviewed. Corresponding respiratory therapy regarding different stages of infection is proposed. Infection control principles and respiratory strategies including oxygen therapy, non-invasive respiratory support (NIRS), intubation evaluation, equipment preparation, ventilator settings, special maneuvers comprise of the prone position (PP), recruitment maneuver (RM), extracorporeal membrane oxygenation (ECMO), weaning and extubation are summarized. Respiratory equipment and device disinfection recommendations are worked up. We expect this review article could be used as a reference by healthcare workers in patient care while minimizing the risk of environmental contamination.

Intelligent disinfection robots assist medical institutions in controlling environmental surface disinfection

In recent years, noncontact crewless operations have become prominent in the field of environmental disinfection. Robots that automatically disinfect the air and surfaces of hospital environments can help reduce the human resources spent on environmental cleaning and disinfection and minimize the risk of occupational exposure for staff. These robots also facilitate informatized management of environmental disinfection, reduce costs, and increase the efficiency of disinfection efforts.

Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomized, double-blind, placebo-controlled phase 2 trial.

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Detection of the Novel SARS-CoV-2 European Lineage B.1.177 in Ontario, Canada (preprint)

Background: Travel-related dissemination of SARS-CoV-2 continues to contribute to the global pandemic. A novel SARS-CoV-2 lineage (B.1.177) reportedly arose in Spain in the summer of 2020, with subsequent spread across Europe linked to travel by infected individuals. Surveillance and monitoring through the use of whole genome sequencing (WGS) offers insights into the global and local movement of pathogens such as SARS-CoV-2 and can detect introductions of novel variants. Methods: We analyzed the genomes of SARS-CoV-2 sequenced for surveillance purposes from specimens received by Public Health Ontario (Sept 6 - Oct 10, 2020), collected from individuals in eastern Ontario. Taxonomic lineages were identified using pangolin (v2.08) and phylogenetic analysis incorporated publicly available genomes covering the same time period as the study sample. Epidemiological data collected from laboratory requisitions and standard reportable disease case investigation was integrated into the analysis. Results: Genomic surveillance identified a COVID-19 case with SARS-CoV-2 lineage B.1.177 from an individual in eastern Ontario in late September, 2020. The individual had recently returned from Europe. Genomic analysis with publicly available data indicate the most closely related genomes to this specimen were from Southern Europe. Genomic surveillance did not identify further cases with this lineage. Conclusions: Genomic surveillance allowed for early detection of a novel SARS-CoV-2 lineage in Ontario which was deemed to be travel related. This type of genomic-based surveillance is a key tool to measure the effectiveness of public health measures such as mandatory self-isolation for returned travellers, aimed at preventing onward transmission of newly introduced lineages of SARS-CoV-2.

COVID-19 Clinical Trials Registered Worldwide for Drug Intervention: An Overview and Characteristic Analysis.

OBJECTIVE: This study aims to comprehensively evaluate the characteristics of clinical drug trials to facilitate the collection of evidence for COVID-19 drug treatments. METHODS: A retrospective analysis of 910 trials retrieved on August 7, 2020. RESULTS: A total of 910 registered clinical trials with at least one drug intervention were evaluated. The number of registrations (32.4%, 295) from the United States accounted for nearly one-third of the total and far exceeded that of other countries individually. Furthermore, the peak number of trials were registered in April (34.3%, 312). Over half of the trials (51.2%, 466) are in the recruitment phase, and only 4.2% (38) of the trials have been completed. The median (interquartile range) estimated enrollment is 127 (59, 365). In 39% (355) of trials, the estimated enrollment is less than 100 participants. A total of 94.5% (790) of the trials use randomization in the allocation, 82.7% (753) use a parallel intervention mode, and 52.2% (475) use masking. A total of 287 drug names have been standardized and mapped. "Hydroxychloroquine" is the leading drug among the registered trials (7.47%, 68). Among the main countries contributing to investigations on "hydroxychloroquine", the United States ranks first with 36.76% (25) of the trials. CONCLUSION: The designs of COVID-19 clinical drug trials have greatly improved in terms of the implementation of randomization and, particularly, blinding methods. In terms of drug reuse, the number of drug types has greatly increased, and hundreds of drugs have been used for efficacy screening. The emergence of large-sample registration trials is expected to address the uncertainty regarding the current clinical efficacy of some drugs.

Epidemiological characteristics of the clusters of COVID-19 in Xi'an

Objective: To explore the transmission characteristics of the typical clusters of coronavirus diseases 2019 (COVID-19) in Xi'an, so as to provide scientific basis for optimizing the control strategy of COVID-19.

Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 During the Pandemic Crisis.

Two phase-III, double-blind, randomized clinical trials of remdesivir plus SOC (standard of care) versus placebo plus SOC have been conducted in Wuhan hospitals by Chinese investigators during the urgent COVID-19 epidemic [ClincalTrials.gov NCT04257656 and NCT04252664]. These trials have been highly anticipated worldwide. We expect investigators of the trials will soon report the clinical and laboratory findings from the medical perspective. This manuscript provides documentary style information on the process of monitoring key data and making recommendations to the sponsor and investigators based on analytical insights when dealing with the emergent situation from the statistical viewpoint. Having monitored data sequentially from 237 patients, we comment on the strength and weakness of the study design and suggest the treatment effect of remdesivir on severe COVID-19 cases. Our experience with using the Dynamic Data Monitoring (DDM) tool has demonstrated its efficiency and reliability in supporting DSMB's instantaneous review of essential data during the emergent situation. DDM, when used properly by disciplined statisticians, has shown its capability of exploring the trial data flexibly and, in the meantime, protecting the trial's scientific integrity.

Core Outcome Set for Clinical Trials on Coronavirus Disease 2019 (COS-COVID).

Since its outbreak in December 2019, a series of clinical trials on coronavirus disease 2019 (COVID-19) have been registered or carried out. However, the significant heterogeneity and less critical outcomes of such trials may be leading to a waste of research resources. This study aimed to develop a core outcome set (COS) for clinical trials on COVID-19 in order to tackle the outcome issues. The study was conducted according to the Core Outcome Measures in Effectiveness Trials (COMET) Handbook: Version 1.0, a guideline for COS development. A research group was set up that included experts in respiratory and critical medicine, traditional Chinese medicine (TCM), evidence-based medicine, clinical pharmacology, and statistics, in addition to medical journal editors. Clinical trial registry websites (www.chictr.org.cn and clinicaltrials.gov) were searched to retrieve clinical trial protocols and outcomes in order to form an outcome pool. A total of 78 clinical trial protocols on COVID-19 were included and 259 outcomes were collected. After standardization, 132 outcomes were identified within seven different categories, of which 58 were selected to develop a preliminary outcome list for further consensus. After two rounds of Delphi survey and one consensus meeting, the most important outcomes for the different clinical classifications of COVID-19 were identified and determined to constitute the COS for clinical trials on COVID-19 (COS-COVID). The COS-COVID includes one outcome for the mild type (time to 2019 novel coronavirus (2019-nCoV) reverse transcription-polymerase chain reaction (RT-PCR) negativity), four outcomes for the ordinary type (length of hospital stay, composite events, score of clinical symptoms, and time to 2019-nCoV RT-PCR negativity), five outcomes for the severe type (composite events, length of hospital stay, arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2), duration of mechanical ventilation, and time to 2019-nCoV RT-PCR negativity), one outcome for critical type (all-cause mortality), and one outcome for rehabilitation period (pulmonary function). The COS-COVID is currently the most valuable and practical clinical outcome set for the evaluation of intervention effect, and is useful for evidence assessment and decision-making. With a deepening understanding of COVID-19 and application feedback, the COS-COVID should be continuously updated.

Discussion on the Management of Fever Clinic during the Epidemic Period of Corona Virus Disease 2019 / 中华急诊医学杂志

Objective@#To investigate the role of epidemiological history in the screening of Corona Virus Disease 2019 (COVID-19) in fever clinic, to improve the efficiency in fever clinic and reduce the incidence of cross infection.@*Methods@#This is a retrospective study. Patients who were admitted to the fever clinic in West China Hospital of Sichuan University from January 23th, 2020 to February 11th, 2020 included the study. According to epidemiological history, the patients were divided into epidemiological history group (the experimental group) and no epidemiological history group (the control group). The two groups of patients were admitted and treated separately. The clinical data, NEWS score, etiology results, viral pneumonia showed on CT, time of visit, COVID-19 patient ratio, and admission composition ratio were compared between the two groups. The measurement data were presented as the mean ± standard deviation (SD), and the numeration data were expressed as ratio or constituent ratio. The measurement data of normal distribution between the two groups were compared by independent sample t test. The measurement data of skewed distribution are expressed by the median (interquartile range), and the comparison between the two groups is tested by non-parameter. The differences between enumeration data were assessed by chi-square test. A P<0.05 was considered statistically significant.@*Results@#A total of 2423 patients were included, including 927 patients in the experimental group and 1296 patients in the control group. There were no significant differences in gender, NEWS score and clinical symptoms between the two groups (P> 0.05). The age (35.00 ± 12.80 vs 38.13 ± 15.57 years) , the proportion of fever patients (28.80% vs 32.75%) and waiting time (31.72 vs 58.08 min) of the experimental group were lower than the control group, the difference was statistically significant (P <0.05). The CT examination ratio (37.54% vs 20.39%), viral pneumonia ratio showed on CT (9.77% vs 2.95%), ratio of examined COVID-19 nucleic acid test (85.44% vs 56.75%), and the admission ratio (16.72% vs 9.63%) of the experimental group were higher than the control group, and the differences were statistically significant (P <0.05); There was no significant difference in the positive rates of influenza virus and rhinovirus between the two groups (P> 0.05).@*Conclusion@#It is necessary to adjust the management mode of fever clinic during the Corona Virus Disease 2019, and to manage the patients according to the epidemiological history which can improve the screening efficiency and reduce the risk of cross infection.