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      COVID-19 induces a hyperactive phenotype in circulating platelets

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          Abstract

          Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.

          Abstract

          The reason for the increased thrombotic risk associated with SARS-CoV-2 infection remains unclear. This study reveals that disease severity is associated with increased mean platelet volume and decreased platelet:neutrophil ratio; moreover, all COVID-19 patients possess hyperactive circulating platelets, with agonist-induced ADP release 30-to-90 fold higher than controls.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysis
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                17 February 2021
                February 2021
                17 February 2021
                : 19
                : 2
                : e3001109
                Affiliations
                [1 ] Conway SPHERE Research Group, Conway Institute, University College Dublin, Dublin Ireland
                [2 ] School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
                [3 ] Department of Respiratory Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
                [4 ] School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland
                [5 ] Department of Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
                [6 ] School of Medicine, University College Dublin, Dublin, Ireland
                [7 ] Department of Paediatrics, Royal College of Surgeons in Ireland, Dublin, Ireland
                [8 ] SAS UK Headquarters, Wittington House, Henley Road, Medmenham, Marlow, Buckinghamshire, United Kingdom
                [9 ] SAS Institute Ltd, Dublin, Ireland
                [10 ] UCD Centre for Experimental Pathogen and Host Research, Dublin, Ireland
                [11 ] Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland
                [12 ] Department of Critical Care Medicine, Mater Misericordiae University Hospital, Dublin, Ireland
                [13 ] Department of Infectious Diseases, St Vincent’s University Hospital, Dublin, Ireland
                [14 ] Department of Haematology, Rotunda Hospital, Dublin, Ireland
                [15 ] UCD Institute for Discovery, University College Dublin, Dublin, Ireland
                Leiden University Medical Center: Leids Universitair Medisch Centrum, NETHERLANDS
                Author notes

                The authors have declared that no competing interests exist.

                ¶ Membership of the COCOON Study is provided in the Acknowledgements.

                Author information
                https://orcid.org/0000-0002-5958-6670
                https://orcid.org/0000-0002-7018-5325
                https://orcid.org/0000-0001-9210-9406
                https://orcid.org/0000-0002-9611-8606
                https://orcid.org/0000-0002-6654-4057
                https://orcid.org/0000-0002-0362-3778
                Article
                PBIOLOGY-D-20-02311
                10.1371/journal.pbio.3001109
                7920383
                33596198
                89f8e14d-753e-48e6-b6fe-47849913c640
                © 2021 Comer et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 July 2020
                : 22 January 2021
                Page count
                Figures: 3, Tables: 1, Pages: 15
                Funding
                Funded by: Science Foundation Ireland
                Award ID: 20/COV/0157
                Award Recipient :
                This research was funded by a COVID-19 Rapid Response grant (20/COV/0157) from Science Foundation Ireland awarded to BK, FNÁ and PBM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Covid 19
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Platelets
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Platelets
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Platelets
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Platelets
                Medicine and Health Sciences
                Hematology
                Blood Coagulation
                Platelet Activation
                Medicine and Health Sciences
                Diagnostic Medicine
                Virus Testing
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Secretion
                Medicine and Health Sciences
                Hematology
                Blood Coagulation
                Coagulation Disorders
                Thrombosis
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Coagulation Disorders
                Thrombosis
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Coagulation Disorders
                Thrombosis
                Medicine and Health Sciences
                Vascular Medicine
                Thrombosis
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Antiplatelet Therapy
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Custom metadata
                vor-update-to-uncorrected-proof
                2021-03-01
                All relevant data are within the paper and its Supporting Information files.

                Life sciences
                Life sciences

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