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1.
Reactive and Functional Polymers ; 175:105268, 2022.
Article in English | ScienceDirect | ID: covidwho-1796182

ABSTRACT

The global spread of COVID-19 continues, industrial raw material production is being tested, and the fracturing cost of oil and gas fields continues to rise, posing new challenges to polymer fracturing fluids. A new hydrophobic association polymer PDMA1 with a double tailed monomer structure was synthesized inside this study. Fourier infrared spectroscopy, Electron microscope scanning, Fluorescence spectroscopy, and polymer viscoelasticity were used to investigate the polymer's basic properties. Finally, using molecular dynamics simulation tools, the network structure of PDMA1 was discovered to be more temperature resistant than that of HPAM. PDMA1 has larger hydrodynamic dimensions than HPAM at the same temperature, its radius of gyration is more than HPAM, and its viscosity is greater than HPAM under the same conditions. This provides an additional avenue of investigation for temperature-resistant hydrophobically associating polymers.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-331565

ABSTRACT

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. A recent study found that TRIM7 inhibits human enteroviruses through ubiquitination and proteasomal degradation of viral 2BC protein by targeting the 2C moiety of 2BC protein. Here, we report the crystal structures of TRIM7 in complex with 2C, where the C-terminal region of 2C is inserted into a positively charged groove of the TRIM7 PRY-SPRY domain. Structure-guided biochemical studies revealed the C-terminus glutamine residue of 2C as the primary determinant for TRIM7 binding. Such a glutamine-end motif binding mechanism can be successfully extended to other substrates of TRIM7. More importantly, leveraged by this finding, we were able to identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. We further show that TRIM7 may function as a restriction factor to promote the degradation of the viral proteins of norovirus and SARS-CoV-2, thereby restoring the Type I interferon immune response and inhibiting viral infection. Several crystal structures of TRIM7 in complex with SARS-CoV-2 proteins are also determined, and a conserved C-terminus glutamine-specific interaction is observed. These findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.

3.
Acta Pharm Sin B ; 12(7): 2969-2989, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1756265

ABSTRACT

Patients exhibit good tolerance to messenger ribonucleic acid (mRNA) vaccines, and the choice of encoded molecules is flexible and diverse. These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex (MHC) restriction, are relatively easy to control and can be rapidly mass produced. In 2021, the U.S. Food and Drug Administration (FDA) approved the first mRNA-based coronavirus disease 2019 (COVID-19) vaccine produced by Pfizer and BioNTech, which has generated enthusiasm for mRNA vaccine research and development. Based on the above characteristics and the development of mRNA vaccines, mRNA cancer vaccines have become a research hotspot and have undergone rapid development, especially in the last five years. This review analyzes the advances in mRNA cancer vaccines from various perspectives, including the selection and expression of antigens/targets, the application of vectors and adjuvants, different administration routes, and preclinical evaluation, to reflect the trends and challenges associated with these vaccines.

4.
J Am Chem Soc ; 144(13): 5702-5707, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1713118

ABSTRACT

The rapid emergence and spread of escaping mutations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has significantly challenged our efforts in fighting against the COVID-19 pandemic. A broadly neutralizing reagent against these concerning variants is thus highly desirable for the prophylactic and therapeutic treatments of SARS-CoV-2 infection. We herein report a covalent engineering strategy on protein minibinders for potent neutralization of the escaping variants such as B.1.617.2 (Delta), B.1.617.1 (Kappa), and B.1.1.529 (Omicron) through in situ cross-linking with the spike receptor binding domain (RBD). The resulting covalent minibinder (GlueBinder) exhibited enhanced blockage of RBD-human angiotensin-converting enzyme 2 (huACE2) interaction and more potent neutralization effect against the Delta variant than its noncovalent counterpart as demonstrated on authentic virus. By leveraging the covalent chemistry against escaping mutations, our strategy may be generally applicable for restoring and enhancing the potency of neutralizing antibodies to SARS-CoV-2 and other rapidly evolving viral targets.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/drug therapy , Humans , Neutralization Tests , Pandemics , Protein Binding , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-312665

ABSTRACT

The outbreak of novel coronavirus pneumonia (COVID-19) has caused mortality and morbidity worldwide. Oropharyngeal-swab (OP-swab) sampling is widely used for the diagnosis of COVID-19 in the world. To avoid the clinical staff from being affected by the virus, we developed a 9-degree-of-freedom (DOF) rigid-flexible coupling (RFC) robot to assist the COVID-19 OP-swab sampling. This robot is composed of a visual system, UR5 robot arm, micro-pneumatic actuator and force-sensing system. The robot is expected to reduce risk and free up the clinical staff from the long-term repetitive sampling work. Compared with a rigid sampling robot, the developed force-sensing RFC robot can facilitate OP-swab sampling procedures in a safer and softer way. In addition, a varying-parameter zeroing neural network-based optimization method is also proposed for motion planning of the 9-DOF redundant manipulator. The developed robot system is validated by OP-swab sampling on both oral cavity phantoms and volunteers.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308148

ABSTRACT

Purpose: To assess the psychological effects of the novel coronavirus disease (COVID-19) on medical staff and the general public. Methods: : During the outbreak of COVID-19, an internet-based questionnaire included The Self-rating Depression Scale (SDS), Perceived Stress Scale (PSS-10), and Impact of Event Scale-Revised (IES-R) was used to assess the impact of the epidemic situation on the mental health of medical staff and general population in Wuhan and its surrounding areas. Results: : The results suggest that the outbreak of COVID-19 has affected individuals significantly, the degree of which is related to age, sex, occupation and mental illness. There was a significant difference in PSS-10 and IES-R scores between the medical staff and the general population. The medical staff showed higher PSS-10 scores (16.813 ± 4.87) and IES-R scores (22.40 ± 12.12) compared to members of the general population PSS-10 (14.80 ± 5.60) and IES-R scores (17.89 ± 13.08). However, there was no statistically significant difference between the SDS scores of medical staff (44.52 ± 12.36) and the general public (43.08 ± 11.42). In terms of the need for psychological assistance, 50.97% of interviewees responded that they needed psychological counseling, of which medical staff accounted for 65.87% and non-medical staff accounted for 45.10%. Conclusion: During the ongoing COVID-19 outbreak, great attention should be paid to the mental health of the population, especially medical staff, and measures such as psychological intervention should be actively carried out for reducing the psychosocial effects.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325358

ABSTRACT

This study mainly uses simulation technology to simulate the COVID-19 epidemic in Changsha, Hunan Province, China, and analyze the impact of different prevention and control measures on the epidemic. we Collect the information of all COVID-19 patients in Changsha from January 21, 2020 to March 14, 2020 and relevant policies during the COVID-19 epidemic in Changsha. Established the SEIAR infectious disease dynamics model under natural conditions, and added isolation measures on this basis. Using Anylogic8.5, the COVID-19 epidemic in Changsha City was simulated under various conditions based on the established model.In this study we find that There were 242 COVID-19 patients in Changsha. including 121 males (50%) and 121 females (50%).Most cases occurred between February 6 and February 16. Through the calculation of the R t during the epidemic in Changsha, it is found that it is reasonable to resume work on February 8, because the R t value of Changsha dropped below 1 at this time.The simulation results show that reducing the contact rate of residents and reducing the success rate of virus transmission (wearing masks, disinfection, etc.) can effectively prevent the spread of COVID-19 and significantly reduce the number of peak patients.We believe that the disease is mainly spread by the respiratory tract. Therefore, the simulation results show that whether in the early or mid-stage of the epidemic, quarantining the names of residents or reducing the contact rate of residents is very effective in controlling the COVID-19 epidemic.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325338

ABSTRACT

The aim of this study was to retrospectively analyze chest thin-section high-resolution CT (HRCT) findings for 32 patients with Corona Virus Disease 2019 (COVID-19) and clarify the correlation between CT data and laboratory results. 30 patients presented with abnormal initial CT scans. Of 30 patients, COVID-19 showed the involvement of bilateral lungs in 24 (80%), involvement of more than two lobes in 24 (80%), ground-glass opacities without consolidation in 27 (90%), ground-glass opacities with consolidation in 23 (76.7%), opacities with irregular intralobular lines in 26 (86.7%), opacities with round morphology in 25 (83.3%), and peripheral distribution in 30 (100%). Pleural effusion or mediastinal lymphadenopathy was relatively rare manifestations. Rapidly progression of the disease demonstrated by increasing number and range of ground glass opacities and appearance of consolidations at follow-up CT images in two patients. The CT lung severity score and No. of lobes involved were negatively correlated with lymphocyte count( r =-0.363, P =0.041;r =-0.367, P =0.039, respectively). Chest HRCT of COVID-19 predominantly manifests multiple, round, ground glass opacities with irregular intralobular lines, and peripheral distribution of bilateral lungs. HRCT is a potential tool for early screening, assessing progress, and predicting disease severity of COVID-19.Authors Jie Zhou and Jie Cao contributed equally to this work and are co-first authors.

9.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324990

ABSTRACT

Background: A new infectious disease, Coronavirus disease 2019 (COVID-19) has been first reported during December 2019 in Wuhan, China, cases have been exported to other cities and abroad rapidly. Hunan is the neighboring province of Wuhan, a series of preventive and control measures were taken to control the outbreak of COVID-19. It is critical to assess these measures on the epidemic progression for the benefit of global expectation. Method: A Susceptible-exposed-infections/asymptomatic-removed (SEIAR) model was established to evaluate the effect of preventive measures. Berkeley Madonna 8.3.18 was employed for the model simulation and prediction, and the curve-fitting problem was solved by Runge-Kutta fourth-order method.Results In this study, we found that R t was 2.71 from January 21 to 27 and reduced to 0.21 after January 27, 2020. If measures have not been fully launched, patients in Hunan would reach the maximum (8.96 million) on March 25, 2020, and end in about 208 days;when measures have been fully launched, patients in Hunan would just reach the maximum (699) on February 9, 2020, and end in about 56 days, which was very closed to the actual situation.Conclusion The outbreak of COVID-19 in Hunan, China has been well controlled under current measures, full implementation of measures could reduce the peak value, short the time to peak and duration of the outbreak effectively, which could provide a reference for controlling of COVID-19 for other countries.

10.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324989

ABSTRACT

Background: A new human coronavirus named SARS-CoV-2 emerged during December 2019 in Wuhan, China. Cases have been exported to other Chinese cities and abroad, which may cause the global outbreak. Chang Sha is the nearest provincial capital city to Wuhan, the first case of COVID-19 in Changsha was diagnosed on January 21, 2020. Estimating the transmissibility and forecasting the trend of the outbreak of SARS-CoV-2 under the prevention and control measures in Changsha could inform evidence based decisions to policy makers. Methods: : Data were collected from the Health Commission of Changsha and Hunan Center for Disease Control and Prevention. A Susceptible-exposed-infections/ asymptomatic- removed (SEIAR) model was established to simulate the transmission of SARS-CoV-2 in Changsha. Berkeley Madonna 8.3.18 were employed for the model simulation and prediction, while the curve fitting problem was solved by the Runge-Kutta fourth-order method, with a tolerance of 0.001. Results: : In this study, we found that Rt was 2.05 from January 21 to 27 and reduced to 0.2 after January 27, 2020 in Changsha. The prediction results showed that when no obvious prevention and control measures were applied, the total number of patients in Changsha would reach the maximum (2.27 million) on the 79th day after the outbreak, and end in about 240 days;When measures have not been fully launched, the total number of patients would reach the maximum (1.60 million) on the 28th day after the outbreak, and end in about 110 days;When measures have been fully launched, the total number of patients would reach the maximum (234) on the 23rd day after the outbreak, and end in about 60 days. Conclusions: : Outbreak of SARS-CoV-2 in Changsha is in a controllable stage under current prevention and control measures, it is predicted that the cumulative patients would reach the maximum of 234 on February 12, and the outbreak would be over on 20 March in Changsha. With the fully implementation of prevention and control measures, it could effectively reduce the peak value, short the time to peak and duration of the outbreak.

11.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-323544

ABSTRACT

The coronavirus disease-19 (COVID-19) caused by SARS-CoV-2 infection can lead to a series of clinical settings from non-symptomatic viral carriers/spreaders to severe illness characterized by acute respiratory distress syndrome (ARDS)1,2. A sizable part of patients with COVID-19 have mild clinical symptoms at the early stage of infection, but the disease progression may become quite rapid in the later stage with ARDS as the common manifestation and followed by critical multiple organ failure, causing a high mortality rate of 7-10% in the elderly population with underlying chronic disease1-3. The pathological investigation in the lungs and other organs of fatal cases is fundamental for the mechanistic understanding of severe COVID-19 and the development of specific therapy in these cases. Gross anatomy and molecular markers allowed us to identify, in two fatal patients subject to necropsy, the main pathological features such as exudation and hemorrhage, epithelium injuries, infiltration of macrophages and fibrosis in the lungs. The mucous plug with fibrinous exudate in the alveoli and the activation of alveolar macrophages were characteristic abnormalities. These findings shed new insights into the pathogenesis of COVID-19 and justify the use of interleukin 6 (IL6) receptor antagonists and convalescent plasma with neutralizing antibodies against SARS-CoV-2 for severe patients.Authors Chaofu Wang, Jing Xie, Lei Zhao, Xiaochun Fei, Heng Zhang, and Yun Tan contributed equally to this work. Authors Chaofu Wang, Jun Cai, Rong Chen, Zhengli Shi, and Xiuwu Bian jointly supervised this work.

12.
Nat Commun ; 13(1): 269, 2022 01 12.
Article in English | MEDLINE | ID: covidwho-1621240

ABSTRACT

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.


Subject(s)
COVID-19/immunology , SARS-CoV-2/physiology , Aged , Autopsy , COVID-19/diagnosis , COVID-19/genetics , COVID-19/virology , China , Diagnosis , Female , Hepatitis A Virus Cellular Receptor 2/genetics , Hepatitis A Virus Cellular Receptor 2/immunology , Humans , Lymphocyte Activation , Lymphocytes/immunology , Male , Middle Aged , Myeloid Cells/immunology , Programmed Cell Death 1 Receptor/genetics , Programmed Cell Death 1 Receptor/immunology , SARS-CoV-2/immunology , Viral Load
13.
Shengwu Gongcheng Xuebao ; - (11):4066, 2021.
Article in English | ProQuest Central | ID: covidwho-1600902

ABSTRACT

Expression and purification of different fragments of the new coronavirus nucleocapsid (N) protein, establish a new coronavirus total antibody fluorescence immunochromatographic method and evaluate the influence of different protein fragments on the method. Using bioinformatics technology to analyze, synthesize, express and purify the N protein sequence, prepare different N protein fragments;use 1-ethyl-(3-dimethylaminopropyl) carbodiimide (1-( 3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) method of fluorescent microspheres coupled with antigen was established to establish a sandwich fluorescence chromatography antibody detection method, and the performance was evaluated respectively. In the prepared 4 N protein fragments, the full-length N protein (N419) is preferably coated, and N412 is labeled with 0.5mol/L NaCl as the optimal combination;the 91-120th amino acid (N412) of the N-terminus of the N antigen is deleted It can reduce 87.5% of non-specific interference;the linear range is 0.312-80U/L, the lowest detection limit is 0.165U/L, and the accuracy is above 95%. The fluorescence immunochromatographic detection method for total antibodies of the new coronavirus established by pairing the N protein fragments has a total coincidence rate of 98% compared with the Guangzhou Wanfu test strip. The improvement provides experimental basis and reference.

14.
Sci Rep ; 11(1): 23127, 2021 11 30.
Article in English | MEDLINE | ID: covidwho-1545642

ABSTRACT

A high-performing interpretable model is proposed to predict the risk of deterioration in coronavirus disease 2019 (COVID-19) patients. The model was developed using a cohort of 3028 patients diagnosed with COVID-19 and exhibiting common clinical symptoms that were internally verified (AUC 0.8517, 95% CI 0.8433, 0.8601). A total of 15 high risk factors for deterioration and their approximate warning ranges were identified. This included prothrombin time (PT), prothrombin activity, lactate dehydrogenase, international normalized ratio, heart rate, body-mass index (BMI), D-dimer, creatine kinase, hematocrit, urine specific gravity, magnesium, globulin, activated partial thromboplastin time, lymphocyte count (L%), and platelet count. Four of these indicators (PT, heart rate, BMI, HCT) and comorbidities were selected for a streamlined combination of indicators to produce faster results. The resulting model showed good predictive performance (AUC 0.7941 95% CI 0.7926, 0.8151). A website for quick pre-screening online was also developed as part of the study.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Humans , Machine Learning , Middle Aged
15.
Sheng Wu Gong Cheng Xue Bao ; 37(11): 4066-4074, 2021 Nov 25.
Article in Chinese | MEDLINE | ID: covidwho-1543003

ABSTRACT

Different fragments of SARS-CoV-2 nucleocapsid (N) protein were expressed and purified, and a fluorescence immunochromatography method for detection of SARS-CoV-2 total antibody was established. The effect of different protein fragments on the performance of the method was evaluated. The N protein sequence was analyzed by bioinformatics technology, expressed in prokaryotic cell and purified by metal ion affinity chromatography column. Different N protein fragments were prepared for comparison. EDC reaction was used to label fluorescence microsphere on the synthesized antigen to construct sandwich fluorescence chromatography antibody detection assay, and the performance was systemically evaluated. Among the 4 prepared N protein fragments, the full-length N protein (N419) was selected as the optimized coating antigen, N412 with 0.5 mol/L NaCl was used as the optimal combination; deleting 91-120 amino acids from the N-terminal of N412 reduced non-specific signal by 87.5%. the linear range of detection was 0.312-80 U/L, the limit of detection was 0.165 U/L, and the accuracy was more than 95%. A fluorescence immunochromatographic detection method for analysis of SARS-CoV-2 total antibody was established by pairing N protein fragments. The detection result achieved 98% concordance with the commercially available Guangzhou Wanfu test strip, which is expected to be used as a supplementary approach for detection of SARS-CoV-2. The assay could also provide experimental reference for improving the performance of COVID-19 antibody detection reagents.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Chromatography, Affinity , Fluorescent Antibody Technique , Humans , Microspheres , Sensitivity and Specificity
16.
Rob Auton Syst ; 148: 103917, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1482947

ABSTRACT

The coronavirus disease 2019 (COVID-19) outbreak has increased mortality and morbidity world-wide. Oropharyngeal swabbing is a well-known and commonly used sampling technique for COVID-19 diagnose around the world. We developed a robot to assist with COVID-19 oropharyngeal swabbing to prevent frontline clinical staff from being infected. The robot integrates a UR5 manipulator, rigid-flexible coupling (RFC) manipulator, force-sensing and control subsystem, visual subsystem and haptic device. The robot has strength in intrinsically safe and high repeat positioning accuracy. In addition, we also achieve one-dimensional constant force control in the automatic scheme (AS). Compared with the rigid sampling robot, the developed robot can perform the oropharyngeal swabbing procedure more safely and gently, reducing risk. Alternatively, a novel robot control schemes called collaborative manipulation scheme (CMS) which combines a automatic phase and teleoperation phase is proposed. At last, comparative experiments of three schemes were conducted, including CMS, AS, and teleoperation scheme (TS). The experimental results shows that CMS obtained the highest score according to the evaluation equation. CMS has the excellent performance in quality, experience and adaption. Therefore, the proposal of CMS is meaningful which is more suitable for robot-sampling.

17.
Front Med (Lausanne) ; 8: 735779, 2021.
Article in English | MEDLINE | ID: covidwho-1470760

ABSTRACT

Objectives: To data, no patients with obvious epidemiological relationship co-infected with SARS-CoV-2 and other pathogens have been reported. Here, we investigated 10 patients caused by co-infection with SARS-CoV-2 and human adenovirus (HAdV), resulting in third-generation transmission. Materials and Methods: From Jan 15, 2020, we enrolled 10 patients with pneumonia in Hunan Province, China. Epidemiological, clinical, and laboratory investigation results from these patients were analyzed. An epidemiological investigation was performed to assess whether patient infections were linked using conventional methods and metagenomic sequencing. Results: The presence of co-infection with SARS-CoV-2 and HAdV was determined via RT-PCR and metagenomic sequencing. Phylogenetic analysis revealed that SARS-CoV-2 and HAdV genomes clustered together, with similar genetic relationships. The first patient likely became co-infected during meetings or travel in Wuhan. The patient transmitted the virus via dinners and meetings, which resulted in four second-generation cases. Then, a second-generation case transmitted the virus to her family members or relatives via presymptomatic transmission. Conclusions: This study described an example of co-infection with SARS-CoV-2 and HAdV in pneumonia patients, which caused third-generation cases and inter-regional transmission via meetings, household interactions, and dinner parties. We also observed the persistent and presymptomatic transmission of co-infection, which has the potential to make the continued control of the COVID-19 pandemic challenging. Continuous surveillance is needed to monitor the prevalence, infectivity, transmissibility, and pathogenicity of SARS-CoV-2 co-infection with other pathogens to evaluate its real risk.

18.
Disease Surveillance ; 36(4):355-359, 2021.
Article in Chinese | GIM | ID: covidwho-1302603

ABSTRACT

Objective: To analyze the infection status of common respiratory pathogens in coronavirus disease 2019 (COVID-19) patients and their family members in Haidian district of Beijing and compare the disease severity between the COVID-19 patients with co-infections and the COVID-19 patients only infected with SARS-CoV-2.

19.
Int J Med Sci ; 18(13): 2789-2798, 2021.
Article in English | MEDLINE | ID: covidwho-1296170

ABSTRACT

Coronavirus disease 2019 (COVID-19) has spread widely in the communities in many countries. Although most of the mild patients could be cured by their body's ability to self-heal, many patients quickly progressed to severe disease and had to undergo treatment in the intensive care unit (ICU). Thus, it is very important to effectively predict which patients with mild disease are more likely to progress to severe disease. A total of 72 patients hospitalized with COVID-19 in Shandong Provincial Public Health Clinical Center and 1141 patients included in the published papers were enrolled in this study. We determined that the combination of interleukin-6 (IL-6), Neutrophil (NEUT), and Natural Killer (NK) cells had the highest prediction accuracy (with 75% sensitivity and 95% specificity) for progression of COVID-19 infection. A binomial regression equation that accounted for a multiple risk score for the combination of IL-6, NEUT, and NK was also established. The multiple risk score is a good indicator for early stratification of mild patients into risk categories, which is very important for adjusting the treatment plan and preventing death.


Subject(s)
Biomarkers/analysis , COVID-19/etiology , Aged , Biomarkers/blood , Blood Cell Count , COVID-19/epidemiology , Comorbidity , Disease Progression , Humans , Interleukin-6/blood , Killer Cells, Natural , Middle Aged , Neutrophils , Retrospective Studies
20.
Cell Res ; 31(8): 836-846, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275907

ABSTRACT

Severe COVID-19 disease caused by SARS-CoV-2 is frequently accompanied by dysfunction of the lungs and extrapulmonary organs. However, the organotropism of SARS-CoV-2 and the port of virus entry for systemic dissemination remain largely unknown. We profiled 26 COVID-19 autopsy cases from four cohorts in Wuhan, China, and determined the systemic distribution of SARS-CoV-2. SARS-CoV-2 was detected in the lungs and multiple extrapulmonary organs of critically ill COVID-19 patients up to 67 days after symptom onset. Based on organotropism and pathological features of the patients, COVID-19 was divided into viral intrapulmonary and systemic subtypes. In patients with systemic viral distribution, SARS-CoV-2 was detected in monocytes, macrophages, and vascular endothelia at blood-air barrier, blood-testis barrier, and filtration barrier. Critically ill patients with long disease duration showed decreased pulmonary cell proliferation, reduced viral RNA, and marked fibrosis in the lungs. Permanent SARS-CoV-2 presence and tissue injuries in the lungs and extrapulmonary organs suggest direct viral invasion as a mechanism of pathogenicity in critically ill patients. SARS-CoV-2 may hijack monocytes, macrophages, and vascular endothelia at physiological barriers as the ports of entry for systemic dissemination. Our study thus delineates systemic pathological features of SARS-CoV-2 infection, which sheds light on the development of novel COVID-19 treatment.


Subject(s)
COVID-19/pathology , Lung/virology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , Autopsy , COVID-19/virology , China , Cohort Studies , Critical Illness , Female , Fibrosis , Hospitalization , Humans , Kidney/pathology , Kidney/virology , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/virology , Lung/pathology , Male , Middle Aged , RNA, Viral/metabolism , SARS-CoV-2/genetics , Spleen/pathology , Spleen/virology , Trachea/pathology , Trachea/virology
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