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1.
J Tradit Complement Med ; 12(1): 73-89, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1814844

ABSTRACT

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. METHODS: The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. RESULTS AND CONCLUSION: We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico. In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant (K d) = 0.468 µM, 1.712 µM, 6.650 µM, 2.86 µM, 3.761 µM and 4.27 µM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50-90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC50 > 100 µM; dioscin and celastrol showed IC50 = 1.5625 µM and 0.9866 µM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. SECTION 1: Natural Products. TAXONOMY CLASSIFICATION BY EVISE: SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study.

3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-319519

ABSTRACT

Multiorgan injuries are a major complication of severe COVID-19;however, its pathogenesis is barely understood. Herein, we profiled the host responses to SARS-CoV-2 infection by performing quantitative proteomics of COVID-19 postmortem samples, and provided a comprehensive proteome map covering the protein alterations in eight different organs/tissues. Our results revealed that lung underwent the most abundant protein alterations mainly enriched in immune-/inflammation-related or morphology-related processes, while surprisingly, other organs/tissues exhibited significant protein alterations mainly enriched in processes related with organ movement, respiration, and metabolism. These results indicate that the major cause of lung injury was excessive inflammatory response, and subsequent intravascular thrombosis and pulmonary architecture/function destruction, while other organs/tissues were mainly injured by hypoxia and functional impairment. Therefore, our findings demonstrate the significant pathophysiological alternations of host proteins/pathways associated with multiorgan injuries of COVID-19, which provides invaluable knowledge about COVID-19-associated host responses and sheds light on the pathogenesis of COVID-19.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317641

ABSTRACT

SARS-CoV-2, the causative agent of coronavirus disease 19 (COVID 19), is responsible for the ongoing pandemic but still lacks approved antivirals. Repurposing pre-existing FDA approved drugs presents a rapid approach for new therapeutic options. In the present study, we report that three pre-existing FDA-approved drugs, i.e., vapreotide, grazoprevir, and simeprevir, inhibit the replication of SARS-CoV-2 in cells. The E50 values of vapreotide, grazoprevir, and simeprevir against SARS-CoV-2 in Vero E6 cells was 3.98 ± 0.35 μM, 2.08 ± 0.13 μM, and 1.41 ± 0.12 μM, respectively. In vitro biochemical experiments further revealed that vapreotide, grazoprevir, and simeprevir efficiently inhibits the unwinding activity of the Nsp13 helicase of SARS-CoV-2 with IC50 values of ⁓10, ⁓2.5, and ⁓1.25 µM, respectively, providing signs for understanding their antiviral mechanism of action. Given their good safety profiles in their original indications, our study offices new insights in repurposing these drugs alone or in combination with other antivirals in the global fighting against SARS-CoV-2.Funding: This work was financially supported by the Youth Innovation Promotion Association CAS (to H.Y.), and the National Natural Science Foundation of China (No. 31770192 and No. 32070187 to H.Y.).Conflict of Interest: The authors declare no competing interests.

6.
Integr Med Res ; 10: 100796, 2021.
Article in English | MEDLINE | ID: covidwho-1499989

ABSTRACT

BACKGROUND: There are several effective complementary and integrative therapies for patients with severe COVID-19. The trial aims to evaluate the efficacy and advantages of the qigong exercise and acupressure rehabilitation program (QARP) for treating patients with severe COVID-19. METHODS: A total of 128 patients with COVID-19 aged 20 to 80 years were recruited and randomly allocated in a 1:1 ratio to receive QARP plus standard therapies or standard therapies alone. QARP consisted of acupressure therapy and qigong exercise (Liu Zi Jue). The primary outcome was measured with the modified Medical Research Council (mMRC) dyspnea scale, and the secondary outcomes included the modified Borg dyspnea scale (MBS), fatigue Scale-14 (FS-14), patient health questionnaire-9 scale (PHQ-9), duration of respiratory symptoms, and vital signs. RESULTS: In total, 128 patients completed the clinical trial. The QARP group and standard therapies group showed significant improvements in vital signs (except blood pressure) and clinical scales compared with baseline (p<0.05). The QARP group also showed more significant improvement in the mMRC dyspnea scale (-1.8 [-2.1, -1.6], p=0.018) and modified Borg dyspnea scale (-3.7 [95% confidence intervals (CI) -4.3, -3.1], p=0.045). The duration of cough was 14.3 days (95% CI 12.6, 16.1, p=0.046), and the length of hospital stay was 18.5 days (95% CI 17.0, 20.0, p=0.042) in the QARP group, both of which were significantly reduced compared with the standard therapies group (p<0.05). CONCLUSION: QARP plus standard therapies improved lung function and symptoms such as dyspnea and cough in patients with severe COVID-19 and shortened the length of hospital stay. Therefore, QARP may be considered an effective treatment option for patients with severe COVID-19. TRIAL REGISTRATION: Clinical Research Information Service Identifier: ChiCTR2000029994.

7.
J Tradit Complement Med ; 12(1): 73-89, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1433611

ABSTRACT

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters cells through the binding of the viral spike protein with human angiotensin-converting enzyme 2 (ACE2), resulting in the development of coronavirus disease 2019 (COVID-19). To date, few antiviral drugs are available that can effectively block viral infection. This study aimed to identify potential natural products from Taiwan Database of Extracts and Compounds (TDEC) that may prevent the binding of viral spike proteins with human ACE2 proteins. METHODS: The structure-based virtual screening was performed using the AutoDock Vina program within PyRX software, the binding affinities of compounds were verified using isothermal titration calorimetry (ITC), the inhibitions of SARS-CoV-2 viral infection efficacy were examined by lentivirus particles pseudotyped (Vpp) infection assay, and the cell viability was tested by 293T cell in MTT assay. RESULTS AND CONCLUSION: We identified 39 natural products targeting the viral receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in silico. In ITC binding assay, dioscin, celastrol, saikosaponin C, epimedin C, torvoside K, and amentoflavone showed dissociation constant (K d) = 0.468 µM, 1.712 µM, 6.650 µM, 2.86 µM, 3.761 µM and 4.27 µM, respectively. In Vpp infection assay, the compounds have significantly and consistently inhibition with the 50-90% inhibition of viral infection efficacy. In cell viability, torvoside K, epimedin, amentoflavone, and saikosaponin C showed IC50 > 100 µM; dioscin and celastrol showed IC50 = 1.5625 µM and 0.9866 µM, respectively. These natural products may bind to the viral spike protein, preventing SARS-CoV-2 from entering cells. SECTION 1: Natural Products. TAXONOMY CLASSIFICATION BY EVISE: SARS-CoV-2, Structure-Based Virtual Screening, Isothermal Titration Calorimetry and Lentivirus Particles Pseudotyped (Vpp) Infection Assay, in silico and in vitro study.

8.
Front Cell Infect Microbiol ; 11: 706252, 2021.
Article in English | MEDLINE | ID: covidwho-1405403

ABSTRACT

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don't know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted via certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.


Subject(s)
COVID-19 , SARS-CoV-2 , Apoptosis , Humans , Membrane Glycoproteins , Nucleocapsid Proteins , Spike Glycoprotein, Coronavirus
10.
Health Promot Perspect ; 11(3): 288-298, 2021.
Article in English | MEDLINE | ID: covidwho-1374787

ABSTRACT

Background: To adapt the scientific evaluation tool for the confusion evaluation of health rumors and to test this tool to the confusion evaluation of coronavirus disease 2019 (COVID-19)-related health rumors on Chinese online platforms during the outbreak period of COVID-19in China. Methods: The design of our study was systematic evaluation of COVID-19-related health rumors. Retrieved from 7 rumor-repellent platforms, rumors about COVID-19 were collected during the publication from December 1, 2019, to February 6, 2020, and their origins were traced. Researchers evaluated rumors using the confusion evaluation tool in 6 dimensions(creators, evidence selection, evidence evaluation, evidence application, backing and publication platform, conflict of interest). Items were scored using a seven-point Likert scale. The scores were converted into percentages, and the median of rumors from different sources was compared with rank-sum test. Results: Our research included 127 rumors. Scores were converted to percentages, median and interquartile range are used to describe the data. The median score: creators 25.00%(interquartile range, IQR, 16.67-37.50%), evidence selection 27.78% (IQR, 13.89-44.44%),evidence evaluation 33.33% (IQR, 25.00-45.83%), evidence application 36.11% (IQR, 22.22-47.22%), backing and publication platform 8.33% (IQR, 4.17-20.83%), conflict of interest75.00% (IQR, 50.00-83.33%). Almost 40% rumors came from WeChat and the rumors with the lowest scores were concentrated on the WeChat platform. The rumors about prevention methods have relatively lower scores. Conclusion: Most rumors included were not highly confusing for evaluators of this project.WeChat is the "worst-hit area" of COVID-19 related health rumors. More than half rumors focus on the description of prevention methods, which reflects the panic, anxiety and blind conformity of the public under public health emergencies.

11.
Bioorg Med Chem Lett ; 48: 128263, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1309173

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 has created an unprecedented global health emergency. As of July 2021, only three antiviral therapies have been approved by the FDA for treating infected patients, highlighting the urgent need for more antiviral drugs. The SARS-CoV-2 3CL protease (3CLpro) is deemed an attractive drug target due to its essential role in viral polyprotein processing and pathogenesis. Indeed, a number of peptidomimetic 3CLpro inhibitors armed with electrophilic warheads have been reported by various research groups that can potentially be developed for treating COVID-19. However, it is currently impossible to compare their relative potencies due to the different assays employed. To solve this, we conducted a head-to-head comparison of fifteen reported peptidomimetic inhibitors in a standard FRET-based SARS-CoV-2 3CLpro inhibition assay to compare and identify potent inhibitors for development. Inhibitor design and the suitability of various warheads are also discussed.


Subject(s)
Antiviral Agents/chemistry , Coronavirus 3C Proteases/antagonists & inhibitors , Cysteine Proteinase Inhibitors/chemistry , Peptidomimetics/chemistry , SARS-CoV-2/enzymology , Antiviral Agents/metabolism , Coronavirus 3C Proteases/metabolism , Cysteine Proteinase Inhibitors/metabolism , Enzyme Assays , Fluorescence Resonance Energy Transfer , Inhibitory Concentration 50 , Peptidomimetics/metabolism , Protein Binding
12.
Eur Geriatr Med ; 12(3): 609-617, 2021 06.
Article in English | MEDLINE | ID: covidwho-1144432

ABSTRACT

PURPOSE: We share our strategies for preventing the COVID-19 outbreak in a nursing home in Taiwan. METHODS: We compared the number of outpatient department visits, the days of prescription from the outpatient department, the number of emergency department visits of the nursing home residents and staff, the number of admissions, and the days of admission of the residents for respiratory tract infection treatment between 2019 and 2020 to examine the effect of our preventive measures in the nursing home. Residents and staff who continuously lived and worked in the nursing home from 2019 to 2020 were included. The differences in outcomes between 2019 and 2020 were examined using paired sample t tests. The multivariate analyses were presented through generalized estimating equation analysis. RESULTS: A cohort of 183 residents and 127 staff was included and their electronic medical documentation was analyzed in two periods: January-September 2019 and January-September 2020. These residents had lower numbers of outpatient department visits (P < 0.001), days of prescription from the outpatient department (P < 0.001), number of emergency department visits (P < 0.001), number of admissions (P < 0.001), and days of admission (P < 0.001) to treat respiratory tract infections from January-September 2020 than January-September 2019. These staff members had lower numbers of outpatient department visits (P = 0.015) and days of prescription from the outpatient department (P = 0.009) to treat respiratory tract infections from January-September 2020 than January-September 2019. CONCLUSION: The association between our preventive measures and decreasing the risk of respiratory tract infection in nursing home residents and staff could be found. Sharing these experiences is valuable, as they provide important insights related to clinical practice during the COVID-19 pandemic.


Subject(s)
COVID-19 , Infection Control , Nursing Homes , Respiratory Tract Infections , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/prevention & control , Female , Health Personnel/statistics & numerical data , Homes for the Aged , Hospitalization/statistics & numerical data , Humans , Infection Control/methods , Infection Control/statistics & numerical data , Male , Middle Aged , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/prevention & control , Retrospective Studies , SARS-CoV-2 , Taiwan
13.
Hum Genomics ; 15(1): 18, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1136250

ABSTRACT

BACKGROUND: In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people's health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein-protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in. RESULTS: In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients. CONCLUSIONS: In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.


Subject(s)
Bronchi/virology , COVID-19/genetics , Gene Expression Regulation , Bronchi/physiology , Chemokine CXCL10/genetics , Epidermal Growth Factor/genetics , Host-Pathogen Interactions/genetics , Humans , Interleukin-8/genetics , Organoids , Protein Interaction Maps/genetics , Software
14.
Natl Sci Rev ; 7(7): 1157-1168, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1114858

ABSTRACT

The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.

16.
Front Microbiol ; 11: 600989, 2020.
Article in English | MEDLINE | ID: covidwho-1021898

ABSTRACT

SARS-coronavirus-2-induced immune dysregulation and inflammatory responses are involved in the pathogenesis of coronavirus disease-2019 (COVID-19). However, very little is known about immune cell and cytokine alterations in specific organs of COVID-19 patients. Here, we evaluated immune cells and cytokines in postmortem tissues, i.e., lungs, intestine, liver, kidneys, and spleen of three patients with COVID-19. Imaging mass cytometry revealed monocyte, macrophage, and dendritic cell (DC) infiltration in the lung, intestine, kidney, and liver tissues. Moreover, in patients with COVID-19, natural killer T cells infiltrated the liver, lungs, and intestine, whereas B cells infiltrated the kidneys, lungs, and intestine. CD11b+ macrophages and CD11c+ DCs also infiltrated the lungs and intestine, a phenomenon that was accompanied by overproduction of the immunosuppressive cytokine interleukin (IL)-10. However, CD11b+ macrophages and CD11c+ DCs in the lungs or intestine of COVID-19 patients did not express human leukocyte antigen DR isotype. In contrast, tumor necrosis factor (TNF)-α expression was higher in the lungs, intestine, liver, and kidneys, but not in the spleen, of all COVID-19 patients (compared to levels in controls). Collectively, these findings suggested that IL-10 and TNF-α as immunosuppressive and pro-inflammatory agents, respectively,-might be prognostic and could serve as therapeutic targets for COVID-19.

17.
Braz J Cardiovasc Surg ; 36(4): 530-534, 2021 08 06.
Article in English | MEDLINE | ID: covidwho-1000762

ABSTRACT

INTRODUCTION: To investigate the effect of WeChat-based telehealth services on the postoperative follow-up of children who underwent congenital heart surgery during the COVID-19 epidemic. METHODS: This study retrospectively analyzed the clinical and family data of 108 children who underwent congenital heart surgery and underwent remote follow-up via the WeChat platform from December 2019 to March 2020 in our hospital. RESULTS: During the follow-up period, the WeChat platform was used to refer 8 children with respiratory infection symptoms to local hospitals for treatment. Two children with poor incision healing were healed after we used the WeChat platform to guide the parents in dressing the wounds on a regular basis at home. Nutritional guidance was given via the WeChat platform to 13 patients with poor growth and development. The psychological evaluation results of the parents showed that the median (range) SDS score was 43 (34-59), and 7 parents (6.5%) were classified as depressed; the median (range) SAS score was 41 (32-58), and 12 parents (11.1%) were classified as having mild anxiety. CONCLUSION: The use of WeChat-based telehealth services was effective for the remote postoperative follow-up of children who underwent congenital cardiac surgery during the COVID-19 epidemic. Providing WeChat-based telehealth services can reduce the amount of travel required for these children and their families, which is helpful for controlling and preventing the spread of COVID-19.


Subject(s)
COVID-19 , Cardiac Surgical Procedures , Epidemics , Child , Follow-Up Studies , Humans , Retrospective Studies , SARS-CoV-2
18.
Virol Sin ; 35(3): 321-329, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-959357

ABSTRACT

The ongoing outbreak of Coronavirus Disease 2019 (COVID-19) has become a global public health emergency. SARS-coronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.


Subject(s)
Betacoronavirus/metabolism , Bismuth/pharmacology , Methyltransferases/metabolism , Nucleoside-Triphosphatase/drug effects , RNA Helicases/drug effects , Salts/pharmacology , Viral Nonstructural Proteins/metabolism , Adenosine Triphosphatases/drug effects , Adenosine Triphosphatases/metabolism , Betacoronavirus/enzymology , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/virology , Humans , Methyltransferases/genetics , Nucleoside-Triphosphatase/genetics , Nucleoside-Triphosphatase/metabolism , Pandemics , Pneumonia, Viral/virology , RNA Helicases/genetics , RNA Helicases/metabolism , Recombinant Proteins , SARS-CoV-2 , Severe Acute Respiratory Syndrome , Viral Nonstructural Proteins/genetics , Virus Replication
19.
Immunity ; 53(5): 1108-1122.e5, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-880509

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic is a global public health crisis. However, little is known about the pathogenesis and biomarkers of COVID-19. Here, we profiled host responses to COVID-19 by performing plasma proteomics of a cohort of COVID-19 patients, including non-survivors and survivors recovered from mild or severe symptoms, and uncovered numerous COVID-19-associated alterations of plasma proteins. We developed a machine-learning-based pipeline to identify 11 proteins as biomarkers and a set of biomarker combinations, which were validated by an independent cohort and accurately distinguished and predicted COVID-19 outcomes. Some of the biomarkers were further validated by enzyme-linked immunosorbent assay (ELISA) using a larger cohort. These markedly altered proteins, including the biomarkers, mediate pathophysiological pathways, such as immune or inflammatory responses, platelet degranulation and coagulation, and metabolism, that likely contribute to the pathogenesis. Our findings provide valuable knowledge about COVID-19 biomarkers and shed light on the pathogenesis and potential therapeutic targets of COVID-19.


Subject(s)
Coronavirus Infections/blood , Coronavirus Infections/pathology , Plasma/metabolism , Pneumonia, Viral/blood , Pneumonia, Viral/pathology , Adult , Aged , Aged, 80 and over , Betacoronavirus , Biomarkers/blood , Blood Proteins/metabolism , COVID-19 , Coronavirus Infections/classification , Coronavirus Infections/metabolism , Female , Humans , Machine Learning , Male , Middle Aged , Pandemics/classification , Pneumonia, Viral/classification , Pneumonia, Viral/metabolism , Proteomics , Reproducibility of Results , SARS-CoV-2
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