Multi-scenario surveillance of respiratory viruses in aerosols with a sub-single molecule spatial resolution (preprint)

Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-CoV-2 and various respiratory viruses with a sensitivity of 10 copies/mL. When seamlessly integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single molecule spatial resolution of 0.83 copies/m3 for airborne virus surveillance. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission.

Engineering customized viral receptors for various coronaviruses (preprint)

Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus amplification for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as amplification of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.

Engineering customized viral receptors for various coronaviruses (preprint)

Coronaviruses display versatile receptor usage, yet in-depth characterization of coronaviruses lacking known receptor identities has been impeded by the absence of feasible infection models1,2. Here, we developed an innovative strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building receptor frameworks comprising various function modules and generating specific epitope-targeting viral binding domains. We showed the key factors for CVRs to efficiently facilitate spike cleavage, membrane fusion, pseudovirus entry, and authentic virus propagation for various coronaviruses, resembling their native receptors. Applying this strategy, we delineated the accessible receptor binding epitopes for functional SARS-CoV-2 CVR design and elucidated the mechanism of entry supported by an amino-terminus domain (NTD) targeting S2L20-CVR. Furthermore, we created CVR-expressing cells for assessing antibodies and inhibitors against 12 representative coronaviruses from six subgenera, most of which lacking known receptors. Notably, a pan-sarbecovirus CVR supported entry of various sarbecoviruses, as well as propagation of a replicable HKU3 pseudovirus and the authentic strain RsHuB2019A3. Through combining an HKU5-specific CVR with reverse genetics, we successfully rescued and cultured wild-type and fluorescence protein-incorporated HKU5, a receptor-unidentified merbecovirus. Our study demonstrated the great potential of CVR strategy in establishing native receptor-independent infection models, paving the way for studying various viruses that are challenging to culture due to the lack of susceptible cells.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19: a systematic review and meta-analysis (preprint)

Several clinical trials have evaluated the efficacy and safety of baricitinib in COVID-19 patients. Recently, there have been reports on critical patients, which are different from previous research results. Studies were searched in PubMed, Embase, and Cochrane Library databases on January 31, 2023. We performed a meta-analysis to estimate the efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19. This study is registered with INPLASY , number 202310086. A total of 3010 patients were included in our analyses. All included studies were randomized controlled trials or prospective study. There was no difference in 14-day mortality between the two groups (OR 0.23 [95% CI 0.03–1.84], I²=72%, P=0.17). In subgroup analyses we found that baricitinib did not seem to improve significantly in 24-day mortality critically ill patients (OR 0.60 [95% CI 0.35–1.02], I²=0%, P=0.06). Fortunately, baricitinib have led to faster recovery and shorter hospital stays for COVID-19 patients. There were no difference in infections and infestations, major adverse cardiovascular events, deep vein thrombosis and pulmonary embolism. Baricitinib is safe. At the same time, we can find that it reduces the mortality of COVID-19 patients, but the prognosis of the critically ill patients is not significantly improved.

Non-steroidal anti-inflammatory drugs and clinical outcomes in patients with COVID-19

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with coronavirus disease 2019 (COVID-19) has raised great concerns. The effect of NSAIDs on the clinical status of COVID-19 remains in question. Therefore, we performed a post-hoc analysis from the ORCHID trial. Patients with COVID-19 from the ORCHID trial were categorized into two groups according to NSAID use. The 28-day mortality, hospitalized discharge, and safety outcomes with NSAIDs for patients with COVID-19 were analyzed. A total of 476 hospitalized patients with COVID-19 were included;412 patients (86.5%) did not receive NSAIDs, while 64 patients (13.5%) took NSAIDs as regular home medication. Patients who took NSAIDs did not have a significant increase in the risk of 28-day mortality (fully adjusted: hazard ratio [HR]: 1.12, 95% CI: 0.52–2.42) in the Cox multivariate analysis. Moreover, NSAIDs did not decrease hospital discharge through 28 days (fully adjusted: HR: 1.02, 95% CI: 0.75–1.37). The results of a meta-analysis including 14 studies involving 48,788 patients with COVID-19 showed that the use of NSAIDs had a survival benefit (summary risk ratio [RR]: 0.70, 95% CI: 0.54–0.91) and decreased the risk of severe COVID-19 (summary: RR: 0.79, 95% CI: 0.71–0.88). In conclusion, the use of NSAIDs is not associated with worse clinical outcomes, including 28-day mortality or hospital discharge in American adult hospitalized patients with COVID-19. Based on current evidence, the use of NSAIDs is safe and should not be cautioned against during the COVID-19 pandemic. Ongoing trials should further assess in-hospital treatment with NSAIDs for patients with COVID-19.

Determinants restricting ACE2 recognition of MERS-related coronaviruses in bats (preprint)

Phylogenetically distant coronaviruses have evolved to employ ACE2 as their common receptors, including NL63 and many Severe acute respiratory syndrome (SARS) coronavirus-related viruses. Recently, we found two Middle East respiratory syndrome coronaviruses (MERS-CoV)-related bat coronaviruses, NeoCoV and PDF-2180, also use Angiotensin-converting enzyme 2(ACE2) but not MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) for entry. Receptor binding domain (RBD)-binding and pseudovirus entry assays based on a wide range of bat ACE2 orthologs revealed that the two viruses strongly prefer ACE2 from Yangochiropteran bats as compared with Yinpterochiropteran bats, which is not observed in NL63 and SARS-CoV-2. Genetic and structural analyses of the virus-receptor interactions of 50 bat ACE2 orthologs pointed to four crucial host range determinants in two viral binding loops on ACE2. Subsequent functional verifications via mutagenesis on representative ACE2 orthologs confirmed the importance of these determinants on human and bat cells. Remarkably, NeoCoV-T510F, a mutation previously shown to acquire human ACE2 recognition, displayed an expanded potential host range covering most tested bat ACE2, probably due to its reinforced interaction with an evolutionary conserved hydrophobic pocket. Our results elucidated the molecular mechanisms for the species-specific ACE2 usage of MERS-related viruses, offering basic information for assessing the zoonotic risk of these ACE2 utilizing merbecoviruses.

Auxiliary Screening COVID-19 by Serology

Background The 2019 novel coronavirus (COVID-19) pandemic remains rampant in many countries/regions. Improving the positive detection rate of COVID-19 infection is an important measure for control and prevention of this pandemic. This meta-analysis aims to systematically summarize the current characteristics of the auxiliary screening methods by serology for COVID-19 infection in real world. Methods Web of Science, Cochrane Library, Embase, PubMed, CNKI, and Wangfang databases were searched for relevant articles published prior to May 1st, 2022. Data on specificity, sensitivity, positive/negative likelihood ratio, area under curve (AUC), and diagnostic odds ratio (dOR) were calculated purposefully. Results Sixty-two studies were included with 35,775 participants in the meta-analysis. Among these studies, the pooled estimates for area under the summary receiver operator characteristic of IgG and IgM to predicting COVID-19 diagnosis were 0.974 and 0.928, respectively. The IgG dOR was 209.78 (95% CI: 106.12 to 414.67). The IgM dOR was 78.17 (95% CI: 36.76 to 166.25). Conclusion Our findings support serum-specific antibody detection may be the main auxiliary screening methods for COVID-19 infection in real world.

Heavy-tailed distributions of confirmed COVID-19 cases and deaths in spatiotemporal space (preprint)

This paper conducts a systematic statistical analysis of the characteristics of the geographical empirical distributions for the numbers of both cumulative and daily confirmed COVID-19 cases and deaths at county, city, and state levels over a time span from January 2020 to June 2022. The mathematical heavy-tailed distributions can be used for fitting the empirical distributions observed in different temporal stages and geographical scales. The estimations of the shape parameter of the tail distributions using the Generalized Pareto Distribution also support the observations of the heavy-tailed distributions. According to the characteristics of the heavy-tailed distributions, the evolution course of the geographical empirical distributions can be divided into three distinct phases, namely the power-law phase, the lognormal phase I, and the lognormal phase II. These three phases could serve as an indicator of the severity degree of the COVID-19 pandemic within an area. The empirical results suggest important intrinsic dynamics of a human infectious virus spread in the human interconnected physical complex network. The findings extend previous empirical studies and could provide more strict constraints for current mathematical and physical modeling studies, such as the SIR model and its variants based on the theory of complex networks.

Temporal and spatial evolution of the distribution related to the number of COVID-19 pandemic (preprint)

This work systematically conducts a data analysis based on the numbers of both cumulative and daily confirmed COVID-19 cases and deaths in a time span through April 2020 to June 2022 for over 200 countries around the world. Such research feature aims to reveal the temporal and spatial evolution of the country-level distribution observed in COVID-19 pandemic, and obtains some interesting results as follows. (1) The distributions of the numbers for cumulative confirmed cases and deaths obey power-law in early stages of COVID-19 and stretched exponential function in subsequent course. (2) The distributions of the numbers for daily confirmed cases and deaths obey power-law in early and late stages of COVID-19 and stretched exponential function in middle stages. The crossover region between power-law and stretched exponential behaviour seems to depend on the evolution of "infection" event and "death" event. Such observation implies a kind of important symmetry related to the dynamics process of COVID-19 spreading. (3) The distributions of the normalized numbers for each metric show a temporal scaling behaviour in 2-year period, and are well described by stretched exponential function. The observation of power-law and stretched exponential behaviour in such country-level distributions suggests underlying intrinsic dynamics of a virus spreading process in human interconnected society. And thus it is important for understanding and mathematically modeling the COVID-19 pandemic.

Spatial Patterns of the Spread of COVID-19 in Singapore and the Influencing Factors

Exploring the spatial patterns of COVID-19 transmission and its key determinants could provide a deeper understanding of the evolution of the COVID-19 pandemic. The goal of this study is to investigate the spatial patterns of COVID-19 transmission in different periods in Singapore, as well as their relationship with demographic and built-environment factors. Based on reported cases from 23 January to 30 September 2020, we divided the research time into six phases and used spatial autocorrelation analysis, the ordinary least squares (OLS) model, the multiscale geographically weighted regression (MGWR) model, and dominance analysis to explore the spatial patterns and influencing factors in each phase. The results showed that the spatial patterns of COVID-19 cases differed across time, and imported cases presented a random pattern, whereas local cases presented a clustered pattern. Among the selected variables, the supermarket density, elderly population density, hotel density, business land proportion, and park density may be particular fitting indicators explaining the different phases of pandemic development in Singapore. Furthermore, the associations between determinants and COVID-19 transmission changed dynamically over time. This study provides policymakers with valuable information for developing targeted interventions for certain areas and periods.

SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules

As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. However, whether SARS-CoV-2 regulates the stress response pathway to achieve immune evasion remains elusive. In this study, SARS-CoV-2 NSP5 and N protein were found to attenuate antiviral stress granule (avSG) formation. Moreover, NSP5 and N suppressed IFN expression induced by infection of Sendai virus or transfection of a synthetic mimic of dsRNA, poly (I:C), inhibiting TBK1 and IRF3 phosphorylation, and restraining the nuclear translocalization of IRF3. Furthermore, HEK293T cells with ectopic expression of NSP5 or N protein were less resistant to vesicular stomatitis virus infection. Mechanistically, NSP5 suppressed avSG formation and disrupted RIG-I–MAVS complex to attenuate the RIG-I–mediated antiviral immunity. In contrast to the multiple targets of NSP5, the N protein specifically targeted cofactors upstream of RIG-I. The N protein interacted with G3BP1 to prevent avSG formation and to keep the cofactors G3BP1 and PACT from activating RIG-I. Additionally, the N protein also affected the recognition of dsRNA by RIG-I. This study revealed the intimate correlation between SARS-CoV-2, the stress response, and innate antiviral immunity, shedding light on the pathogenic mechanism of COVID-19.

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors (preprint)

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes' S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using 'MERS-CoV-2' with both high fatality and transmission rate.

Close relatives of MERS-CoV in bats use ACE2 as their functional receptors (preprint)

Middle East Respiratory Syndrome coronavirus (MERS-CoV) and several bat coronaviruses employ Dipeptidyl peptidase-4 (DPP4) as their functional receptors. However, the receptor for NeoCoV, the closest MERS-CoV relative yet discovered in bats, remains enigmatic. In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. The two viruses use their spikes' S1 subunit carboxyl-terminal domains (S1-CTD) for high-affinity and species-specific ACE2 binding. Cryo-electron microscopy analysis revealed a novel coronavirus-ACE2 binding interface and a protein-glycan interaction, distinct from other known ACE2-using viruses. We identified a molecular determinant close to the viral binding interface that restricts human ACE2 from supporting NeoCoV infection, especially around residue Asp338. Conversely, NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM). Notably, the infection could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV. Our study demonstrates the first case of ACE2 usage in MERS-related viruses, shedding light on a potential bio-safety threat of the human emergence of an ACE2 using "MERS-CoV-2" with both high fatality and transmission rate.

Demand for longer quarantine period among common and uncommon COVID-19 infections: a scoping review.

BACKGROUND: As one of the non-pharmacological interventions to control the transmission of COVID-19, determining the quarantine duration is mainly based on the accurate estimates of the incubation period. However, patients with coarse information of the exposure date, as well as infections other than the symptomatic, were not taken into account in previously published studies. Thus, by using the statistical method dealing with the interval-censored data, we assessed the quarantine duration for both common and uncommon infections. The latter type includes the presymptomatic, the asymptomatic and the recurrent test positive patients. METHODS: As of 10 December 2020, information on cases have been collected from the English and Chinese databases, including Pubmed, Google scholar, CNKI (China National Knowledge Infrastructure) and Wanfang. Official websites and medias were also searched as data sources. All data were transformed into doubly interval-censored and the accelerated failure time model was applied. By estimating the incubation period and the time-to-event distribution of worldwide COVID-19 patients, we obtain the large percentiles for determining and suggesting the quarantine policies. For symptomatic and presymptomatic COVID-19 patients, the incubation time is the duration from exposure to symptom onset. For the asymptomatic, we substitute the date of first positive result of nucleic acid testing for that of symptom onset. Furthermore, the time from hospital discharge or getting negative test result to the positive recurrence has been calculated for recurrent positive patients. RESULTS: A total of 1920 laboratory confirmed COVID-19 cases were included. Among all uncommon infections, 34.1% (n = 55) of them developed symptoms or were identified beyond fourteen days. Based on all collected cases, the 95th and 99th percentiles were estimated to be 16.2 days (95% CI 15.5-17.0) and 22.9 days (21.7‒24.3) respectively. Besides, we got similar estimates based on merely symptomatic and presymptomatic infections as 15.1 days (14.4‒15.7) and 21.1 days (20.0‒22.2). CONCLUSIONS: There are a certain number of infected people who require longer quarantine duration. Our findings well support the current practice of the extended active monitoring. To further prevent possible transmissions induced and facilitated by such infectious outliers after the 14-days quarantine, properly prolonging the quarantine duration could be prudent for high-risk scenarios and in regions with insufficient test resources.

Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies

SARS-CoV-2 attaches to its host receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of the spike protein. The RBD glycoprotein is a critical target for the development of neutralizing antibodies and vaccines against SARS-CoV-2. However, the high heterogeneity of RBD glycoforms may lead to an incomplete neutralization effect and impact the immunogenic integrity of RBD-based vaccines. Investigating the role of different carbohydrate domains is of paramount importance. Unfortunately, there is no viable method for preparing RBD glycoproteins with structurally defined glycans. Herein we describe a highly efficient and scalable strategy for the preparation of six glycosylated RBDs bearing defined structure glycoforms at T323, N331 and N343. A combination of modern oligosaccharide, peptide synthesis and recombinant protein engineering provides a robust route to deciphering carbohydrate structure?function relationships.

Clinical Management of Gynecological Cancer Patients During COVID-19 Epidemic

During the epidemic of COVID-19, the routine clinical treatment for gynecological cancer patients has been disturbed due to the redistribution of medical resource. Due to the systemic immunosuppression caused by the malignancy and anticancer treatments, gynecological cancer patients are more susceptible to COVID-19. With the improvement of the epidemic, the treatment needs of gynecological cancer patients are extremely strong. During this special period, it should carefully identify fever and respiratory symptoms of gynecological cancer patients receiving chemotherapy, immunotherapy and operations. Therefore, it is quite necessary to carry out comprehensive clinical management. We introduce a clinical management of gynecological cancer patients in three aspects of outpatient, in-hospital and out-of-hospital management during this period, in order to maximize the treatment of tumors and effectively prevent COVID-19.

Performance of Composite Filters Assembled from Multiple Layers of Basic Filtration Media

There is a severe shortage of face masks and N95 respirators due to the current COVID-19 pandemic, particularly in countries that were not well prepared in advance. In order to help ease the supply demands of these resources, a strategy of using multiple layers of basic filtration media to construct a composite filter that can match the particle collection efficiency offered by a N95 filtering facepiece respirator (FFR) is proposed. In this study, the filtration performances of four face masks and one N95 respirator using the same test protocol (as a reference) were first compared. Composite filter samples composed of multiple layers of basic face mask and MERV13 furnace media were then constructed and the filter performance of the composite filters was investigated. As expected, the minimum particle collection efficiency of the N95 respirator media sample was higher than 95% and the efficiency of the samples from the four tested face masks varied from 71.8% to 83.6%. The Figure of Merit (FOM) values of the face mask samples were generally half that of the N95 media sample. It was found that a N95-comparable collection efficiency can be achieved by combining two/three layers of face mask media but at the expense of a higher media pressure drop. Additionally, the composite filter samples made up of three/five layers of MERV13 furnace media could approach the FOM offered by the N95 media without the increased pressure drop. It was also found that the measured collection efficiency of multiple-layered filter media was not equal to the calculated in the test particle size range. Further studies are required to identify the reason(s).

Efficacy and safety of tocilizumab in COVID-19 patients: A Meta-Analysis (preprint)

The therapeutic effect of tocilizumab remains controversial. We aimed to evaluate whether tocilizumab might be beneficial in COVID-19 patients. We searched PubMed, Embase and Cochrane library from inception to June 23, 2020. Summary estimates of overall response rate (ORR) and all-cause death rate in all patients were analyzed. This study was registered with PROSPERO (CRD42020191313). We included data from 28 articles including 991 COVID-19 patients who underwent tocilizumab administration. The pooled ORR was 72% (95% CI, 66-79%) and pooled all-cause death rate was 16% (95% CI, 11-22%). The optimal timing of administration was the 7.15 day from the symptom onset and with the lowest death rate of 13.11%. 562 patients were defined as with severe infection, and the pooled ORR was 78% (95% CI, 70-85%). The pooled ORR of 56 organ transplantation recipients was 53% (95% CI, 26-78%), which was lower than non-transplant patients [75% (95% CI, 69-81%)]. Nearly all studies confirmed the safety of tocilizumab administration. Tocilizumab improves the clinical outcome of COVID-19 patients, especially in severe cases, and the optimal timing of administration may provide the guidance for management. However, tocilizumab may be used with caution in solid transplant recipients for the suboptimal efficacy.

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.