Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines.

The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused devastating impacts on the public health and the global economy. Rapid viral antigenic evolution has led to the continual generation of new variants. Of special note is the recently expanding Omicron subvariants that are capable of immune evasion from most of the existing neutralizing antibodies (nAbs). This has posed new challenges for the prevention and treatment of COVID-19. Therefore, exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In sharp contrast to the massive accumulation of mutations within the SARS-CoV-2 receptor-binding domain (RBD), the S2 fusion subunit has remained highly conserved among variants. Hence, S2-based therapeutics may provide effective cross-protection against new SARS-CoV-2 variants. Here, we summarize the most recently developed broad-spectrum fusion inhibitors (e.g., nAbs, peptides, proteins, and small-molecule compounds) and candidate vaccines targeting the conserved elements in SARS-CoV-2 S2 subunit. The main focus includes all the targetable S2 elements, namely, the fusion peptide, stem helix, and heptad repeats 1 and 2 (HR1-HR2) bundle. Moreover, we provide a detailed summary of the characteristics and action-mechanisms for each class of cross-reactive fusion inhibitors, which should guide and promote future design of S2-based inhibitors and vaccines against new coronaviruses.

A Potent Neutralizing Nanobody Targeting the Spike Receptor-Binding Domain of SARS-CoV-2 and the Structural Basis of Its Intimate Binding.

The continuous spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has raised unprecedented challenges to the human society. Antibodies and nanobodies possessing neutralization activity represent promising drug candidates. In this study, we report the identification and characterization of a potent SARS-CoV-2 neutralizing nanobody that targets the viral spike receptor-binding domain (S-RBD). The nanobody, termed as Nb-007, engages SARS-CoV-2 S-RBD with the two-digit picomolar binding affinity and shows outstanding virus entry-inhibition activity. The complex structure of Nb-007 bound to SARS-CoV-2 S-RBD reveals an epitope that is partially overlapping with the binding site for the human receptor of angiotensin-converting enzyme 2 (ACE2). The nanobody therefore exerts neutralization by competing with ACE2 for S-RBD binding, which is further ascertained by our in-vitro biochemical analyses. Finally, we also show that Nb-007 reserves promising, though compromised, neutralization activity against the currently-circulating Delta variant and that fusion of the nanobody with Fc dramatically increases its entry-inhibition capacity. Taken together, these data have paved the way of developing Nb-007 as a drug-reserve for potential treatment of SARS-CoV-2 related diseases.

An engineered 5-helix bundle derived from SARS-CoV-2 S2 pre-binds sarbecoviral spike at both serological- and endosomal-pH to inhibit virus entry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and related sarbecoviruses enter host cells by receptor-recognition and membrane-fusion. An indispensable step in fusion is the formation of 6-helix bundle by viral spike heptad repeats 1 and 2 (HR1 and HR2). Here, we report the construction of 5-helix bundle (5HB) proteins for virus infection inhibition. The optimal construct inhibits SARS-CoV-2 pseudovirus entry with sub-micromolar IC50. Unlike HR2-based peptides that cannot bind spike in the pre-fusion conformation, 5HB features with the capability of binding to pre-fusion spike. Furthermore, 5HB binds viral HR2 at both serological- and endosomal-pH, highlighting its entry-inhibition capacity when SARS-CoV-2 enters via either cell membrane fusion or endosomal route. Finally, we show that 5HB could neutralize S-mediated entry of the predominant SARS-CoV-2 variants and a wide spectrum of sarbecoviruses. These data provide proof-of-concept evidence that 5HB might be developed for the prevention and treatment of SARS-CoV-2 and other emerging sarbecovirus infections.

The Adverse Reactions of Lianhua Qingwen Capsule/Granule Compared With Conventional Drug in Clinical Application: A Meta-Analysis.

Objectives: Lianhua Qingwen capsule/granule (LHQW) is an innovative patented traditional Chinese medicine with potential curative effects on respiratory diseases. However, no consensus has been reached on the security of LHQW to date. The current meta-analysis was performed to evaluate the safety profile of LHQW in relation to conventional drugs (PROSPERO CRD-42020224180). Methods: Comprehensive document retrieval was performed from both English and Chinese databases. Results were reported as risk ratio (RR) with 95% confidence interval (CI). Subgroup, sensitivity and meta-regression analyses were conducted to explore the possible sources of heterogeneity across eligible studies. Results: In total, 217 experimental studies were included. For pooled studies, the incidence of adverse reactions was lower in the LHQW group than the conventional drug group (RR = 0.63, 95% CI = 0.58-0.69, p < 0.001). In the evaluation of treating disease, significant reduced incidence of adverse reactions during treatment of influenza A (H1N1) and influenza were detected in the LHQW group. In the evaluation of security indexes, LHQW group has a reduced incidence of respiratory system damage, skin and its appendages injury, nervous system damage and gastrointestinal system damage, along with other adverse reactions. Subgroup analysis additionally revealed a reduced incidence of some adverse reactions in the LHQW group compared to the conventional drug group (Rash of skin and its appendage damage, dizziness or headache owing to nervous system damage, nausea or vomiting from gastrointestinal system damage and resurgence of disease from other adverse reactions). Conclusion: The current study provides potential a reference for the security of LHQW. Further long-term high-quality studies are essential to validate our conclusions. Systematic Review Registration: https://clinicaltrials.gov/, CRD-42020224180.

Structural biology of SARS-CoV-2: open the door for novel therapies.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the causative agent of the pandemic disease COVID-19, which is so far without efficacious treatment. The discovery of therapy reagents for treating COVID-19 are urgently needed, and the structures of the potential drug-target proteins in the viral life cycle are particularly important. SARS-CoV-2, a member of the Orthocoronavirinae subfamily containing the largest RNA genome, encodes 29 proteins including nonstructural, structural and accessory proteins which are involved in viral adsorption, entry and uncoating, nucleic acid replication and transcription, assembly and release, etc. These proteins individually act as a partner of the replication machinery or involved in forming the complexes with host cellular factors to participate in the essential physiological activities. This review summarizes the representative structures and typically potential therapy agents that target SARS-CoV-2 or some critical proteins for viral pathogenesis, providing insights into the mechanisms underlying viral infection, prevention of infection, and treatment. Indeed, these studies open the door for COVID therapies, leading to ways to prevent and treat COVID-19, especially, treatment of the disease caused by the viral variants are imperative.

Global Fisheries Responses to Culture, Policy and COVID-19 from 2017 to 2020

Global Fishing Watch (GFW) provides global open-source data collected via automated monitoring of vessels to help with sustainable management of fisheries. Limited previous global fishing effort analyses, based on Automatic Identification System (AIS) data (2017–2020), suggest economic and environmental factors have less influence on fisheries than cultural and political events, such as holidays and closures, respectively. As such, restrictions from COVID-19 during 2020 provided an unprecedented opportunity to explore added impacts from COVID-19 restrictions on fishing effort. We analyzed global fishing effort and fishing gear changes (2017–2019) for policy and cultural impacts, and then compared impacts of COVID-19 lockdowns across several countries (i.e., China, Spain, the US, and Japan) in 2020. Our findings showed global fishing effort increased from 2017 to 2019 but decreased by 5.2% in 2020. We found policy had a greater impact on monthly global fishing effort than culture, with Chinese longlines decreasing annually. During the lockdown in 2020, trawling activities dropped sharply, particularly in the coastal areas of China and Spain. Although Japan did not implement an official lockdown, its fishing effort in the coastal areas also decreased sharply. In contrast, fishing in the Gulf of Mexico, not subject to lockdown, reduced its scope of fishing activities, but fishing effort was higher. Our study demonstrates, by including the dimensions of policy and culture in fisheries, that large data may materially assist decision-makers to understand factors influencing fisheries’ efforts, and encourage further marine interdisciplinary research. We recommend the lack of data for small-scale Southeast Asian fisheries be addressed to enable future studies of fishing drivers and impacts in this region.

Additional Value of Non-contrast Chest CT in the Prediction of Adverse Cardiovascular Events in Patients With Novel Coronavirus Disease 2019 (COVID-19).

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown. Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded. Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R 2 = -0.636, p < 0.001). Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.

Making the dynamic interactive map of COVID-19 by implementation of r software

Objective: To introduce the process and concrete steps of making dynamic interactive disease map using Leaflet program package of R software, and we provide assistance for demonstrating the regional distribution of the disease, epidemic analysis and field disposal.

Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019.

BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated. METHODS: 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed. RESULTS: Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15-39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (P < .001), even in the early phase of 1 week from onset (P = .007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (P = .006). CONCLUSIONS: Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

Clinical characteristics and predictive value of lower CD4+T cell level in patients with moderate and severe COVID-19: a multicenter retrospective study.

BACKGROUND: In December 2019, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei, China. Moreover, it has become a global pandemic. This is of great value in describing the clinical symptoms of COVID-19 patients in detail and looking for markers which are significant to predict the prognosis of COVID-19 patients. METHODS: In this multicenter, retrospective study, 476 patients with COVID-19 were enrolled from a consecutive series. After screening, a total of 395 patients were included in this study. All-cause death was the primary endpoint. All patients were followed up from admission till discharge or death. RESULTS: The main symptoms observed in the study included fever on admission, cough, fatigue, and shortness of breath. The most common comorbidities were hypertension and diabetes mellitus. Patients with lower CD4+T cell level were older and more often male compared to those with higher CD4+T cell level. Reduced CD8+T cell level was an indicator of the severity of COVID-19. Both decreased CD4+T [HR:13.659; 95%CI: 3.235-57.671] and CD8+T [HR: 10.883; 95%CI: 3.277-36.145] cell levels were associated with in-hospital death in COVID-19 patients, but only the decrease of CD4+T cell level was an independent predictor of in-hospital death in COVID-19 patients. CONCLUSIONS: Reductions in lymphocytes and lymphocyte subsets were common in COVID-19 patients, especially in severe cases of COVID-19. It was the CD8+T cell level, not the CD4+T cell level, that reflected the severity of the patient's disease. Only reduced CD4+T cell level was independently associated with increased in-hospital death in COVID-19 patients. TRIAL REGISTRATION: Prognostic Factors of Patients With COVID-19, NCT04292964 . Registered 03 March 2020. Retrospectively registered.

Efficacy of Lianhua Qingwen Compared with Conventional Drugs in the Treatment of Common Pneumonia and COVID-19 Pneumonia: A Meta-Analysis.

METHODS: Seven English and Chinese databases were used to search for qualified experimental studies as of July 27, 2020. All data were extracted directly from the included studies, and no special conversion formula was used. The weighted mean difference (WMD), 95% confidence interval (CI), and odds ratio (OR) were used for evaluation. RESULTS: Forty-two studies involving 3793 subjects met the qualification criteria. For common pneumonia, a short duration of flu-like symptoms (WMD = -1.81, 95% CI = -2.12 to -1.50, P < 0.001), sputum (WMD = -1.10, 95% CI = -1.50 to -0.70, P < 0.001), pulmonary rale (WMD = -2.03, 95% CI = -2.74 to -1.31, P < 0.001), pulmonary imaging improvement (WMD = -1.88, 95% CI = -2.28 to -1.47, P < 0.001), curative effect (OR = 3.65, 95% CI = 2.81 to 4.76, P < 0.001), and healing period (WMD = -1.68, 95% CI = -2.62 to -0.74, P < 0.001) were associated with the Lianhua Qingwen group; subgroup analysis based on flu-like symptoms showed statistically significant improvements in fever and cough. For COVID-19 pneumonia, improvements in flu-like symptoms (OR = 3.18, 95% CI = 2.36 to 4.29, P < 0.001), shortness of breath (OR = 10.62, 95% CI = 3.71 to 30.40, P < 0.001), curative effect (OR = 2.49, 95% CI = 1.76 to 3.53, P < 0.001), healing period (WMD = -2.06, 95% CI = -3.36 to -0.75, P = 0.002), and conversion of severe cases (OR = 0.46, 95% CI = 0.27 to 0.77, P = 0.003) were associated with the Lianhua Qingwen group; subgroup analysis indicated statistically significant improvements of fever, cough, fatigue, and muscle pain in the Lianhua Qingwen group compared to the conventional drug group. Regarding adverse reactions, no significant difference was detected for common pneumonia (OR = 0.75, 95% CI = 0.54 to 1.05, P = 0.097). CONCLUSIONS: Lianhua Qingwen combined with conventional drugs may be a promising therapy for treating common pneumonia and COVID-19 pneumonia.

Public Awareness and Mask Usage during the COVID-19 Epidemic: A Survey by China CDC New Media.

An online survey conducted March 18-19, 2020 on the official China CDC WeChat account platform was used to evaluate the effect of public education about masks usage during the new coronavirus disease 2019 (COVID-19) epidemic. Chinese nationals older than 18 were eligible for the survey. The survey collected 5,761 questionnaires from the 31 provinces, municipalities, and autonomous regions of mainland China. 99.7% and 97.2% of the respondents answered correctly that respiratory droplets and direct contact were the main transmission routes. 73.3% of the respondents considered COVID-19 to be 'serious' or 'very serious'. When going to the hospital, 96.9% (2,885/2,976 had gone to a hospital) used a mask during the COVID-19 epidemic, while 41.1% (2,367/5,761) did not use a mask before the epidemic. Among the respondents that used public transportation and went shopping, 99.6% and 99.4%, respectively, wore masks. Among respondents who returned to work, 75.5% wore a mask at the workplace, while 86.3% of those who have not returned to work will choose to use masks when they return to the workplace. The Chinese public is highly likely to use a mask during COVID-19 epidemic, and the mask usage changed greatly since the COVID-19 outbreak. Therefore, public education has played an important role during the COVID-19 epidemic.

Clinical characteristics of pediatric cases of SARS-CoV-2 infection in Hunan, China: A retrospective, multi-center case series (preprint)

Objective To investigate the epidemiological characteristics, clinical features, treatment and short-term prognosis of SARS-CoV-2 infection in children.Methods A retrospective analysis was conducted in children with SARS-CoV-2 admitted to twelve hospitals in eight cities in Hunan province, China, from January 26, 2020 to June 30, 2020.Results A total of 48 children were enrolled in this study. 11 cases (23%) were asymptomatic, 15 cases (31%) were mild, 20 cases (42%) were moderate, and 2 cases (4%) were severe. No children were critical requiring intensive care. The most common symptom was fever (42%), cough (40%), fatigue (17%) and diarrhea (10%). The total peripheral blood leukocytes count decreased in two case (4%), Lymphocytopenia was present in 5 cases (10%). There were abnormal chest CT changes in 22 children (46%), including 15 (68%) with patchy ground glass opacity. In addition to supportive treatment, 41 children (85%) received antiviral therapy, 11 patients and (23%) were treated with antibiotics, 2 children (4%) were treated with methylprednisolone and IVIG. There was no death occurred.Conclusions Most children with SARS CoV-2 infection in Hunan province were asymptomatic, mild or moderate. Severe cases are rare. Close family contact was the main route of infection. The younger the age, the less obvious symptoms for children might be. Epidemiological history, nucleic acid test and chest imaging were important tools for the diagnosis in children.

Epidemiological characteristics of COVID-19 in Hainan Province, China

The epidemiology characteristics of 2019 novel coronavirus diseases (COVID-19) cases in Hainan were collected and analyzed for providing next stage control and prevention strategy in next stage. Spatial and temporal distribution, population characteristic, cluster, the interval between onset, visiting clinic, admitted were analyzed. Local cases and severe cases were also included in the analysis. Result showed that a total of 168 confirmed cases, including 36 severe cases and 5 fatal cases were reported. Cases were mainly distributed in Haikou, Sanya etc tourism cities and counties. The first case occurred in Jan 13th and the epidemic peak occurred in Jan 24th. Since Feb 6th, onset of illness has declined. The male-to-female ratio was 0.9:1. The median age was 51 years. Cases older than 50 years accounted for 54.8%. Retirees accounted for 36.9%, which was highest in all cases. Since Feb, the proportion of local cases rose dramatically. The period from onset to visiting clinic (OTV), from first visiting clinic to diagnosis (VTF), from onset to diagnosis (OTD) and from onset to be admitted (OTA) was longer in local cases than imported cases. Median age and the percentage of underlying diseases of severe/extreme cases were higher than mild/ordinary cases. OTV of severe/extreme cases was longer than mild/ordinary cases, while for VTF, the former was shorter than latter. The epidemic was divided into three stages. Most of cases in the first stage were imported cases, while in the second stage most of cases were local cases. There were few cases in the third stages. We should strengthen personal protection and health monitoring for people in service industry, isolate the close contacts, and carry out publicity and education to raise the awareness of medical treatment for people, especially for old people. Clinical doctors should monitor the state of the patients older than 60 years and with underlying diseases. We should step up epidemic monitoring prevention and control measure for people return from holiday and immigrant to consolidate the effects of prevention and control work.

Overview of lethal human coronaviruses.

Coronavirus infections of multiple origins have spread to date worldwide, causing severe respiratory diseases. Seven coronaviruses that infect humans have been identified: HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2. Among them, SARS-CoV and MERS-CoV caused outbreaks in 2002 and 2012, respectively. SARS-CoV-2 (COVID-19) is the most recently discovered. It has created a severe worldwide outbreak beginning in late 2019, leading to date to over 4 million cases globally. Viruses are genetically simple, yet highly diverse. However, the recent outbreaks of SARS-CoV and MERS-CoV, and the ongoing outbreak of SARS-CoV-2, indicate that there remains a long way to go to identify and develop specific therapeutic treatments. Only after gaining a better understanding of their pathogenic mechanisms can we minimize viral pandemics. This paper mainly focuses on SARS-CoV, MERS-CoV, and SARS-CoV-2. Here, recent studies are summarized and reviewed, with a focus on virus-host interactions, vaccine-based and drug-targeted therapies, and the development of new approaches for clinical diagnosis and treatment.

Prognostic value of NT-proBNP in patients with severe COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury is a common condition among the hospitalized patients with COVID-19. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of severe COVID-19 patients was unknown. METHODS: The study initially enrolled 102 patients with severe COVID-19 from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. The primary outcome was in-hospital death defined as the case fatality rate. Research information and following-up data were obtained from their medical records. RESULTS: The best cut-off value of NT-proBNP for predicting in-hospital death was 88.64 pg/mL with the sensitivity for 100% and the specificity for 66.67%. Patients with high NT-proBNP values (> 88.64 pg/mL) had a significantly increased risk of death during the days of following-up compared with those with low values (≤88.64 pg/mL). After adjustment for potential risk factors, NT-proBNP was independently correlated with in-hospital death. CONCLUSION: NT-proBNP might be an independent risk factor for in-hospital death in patients with severe COVID-19. TRIAL REGISTRATION: ClinicalTrials, NCT04292964. Registered 03 March 2020.

Prediction of fatal adverse prognosis in patients with fever-related diseases based on machine learning: A retrospective study.

BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients' data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination (RFE) method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the Logistic regression were cardiac troponin T (CTnT) (coefficient=0.346, OR = 1.413), temperature (T) (coefficient=0.235, OR = 1.265), respiratory rate (RR) (coefficient= -0.206,OR = 0.814), serum kalium (K) (coefficient=0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient= -0.101, OR = 0.904), and albumin (ALB) (coefficient= -0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heartrate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.