{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:13:46Z","timestamp":1790820826610,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National Early Warning Score 2 (NEWS\u20102) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020\u2010000936\u201023) randomly assigned to either standard of care (SoC) or SoC\u2009+\u2009remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS\u20102 score lower than 3 (in patients with NEWS\u20102\u2009&lt;7 at hospitalization) or 5 (in patients with NEWS\u20102 \u22657 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS\u20102. However, simulations predicted that antiviral activity greater than 99% could reduce by 2\u2009days the time to clinical improvement in patients with high viral load, irrespective of the NEWS\u20102 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.<\/jats:p>","DOI":"10.1002\/psp4.13051","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T09:24:07Z","timestamp":1695201847000},"page":"2027-2037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association between SARS\u2010CoV\u20102 viral kinetics and clinical score evolution in hospitalized patients"],"prefix":"10.1002","volume":"12","author":[{"given":"Nad\u00e8ge","family":"N\u00e9ant","sequence":"first","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Lingas","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-6126","authenticated-orcid":false,"given":"Alexandre","family":"Gaymard","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Institut des Agents Infectieux de Lyon Centre National de R\u00e9f\u00e9rence des Virus Respiratoires France Sud, Hospices Civils de Lyon  Lyon France"},{"name":"Laboratoire Virpath Universit\u00e9 de Lyon, Virpath, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon, Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drifa","family":"Belhadi","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"},{"name":"D\u00e9partement d'\u00c9pid\u00e9miologie AP\u2010HP, H\u00f4pital Bichat, Biostatistique et Recherche Clinique  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Hites","sequence":"additional","affiliation":[{"name":"H\u00f4pital de Bruxelles\u2010\u00c9rasme Universit\u00e9 Libre de Bruxelles, Clinique des Maladies Infectieuses  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9r\u00e8se","family":"Staub","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de Luxembourg, Service des Maladies Infectieuses  Luxembourg Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Greil","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III with Haematology, Medical Oncology, Aemostaseology, Infectiology and Rheumatology, Oncologic Center Salzburg Cancer Research Institute\u2013Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University Salzburg  Salzburg Austria"},{"name":"Cancer Cluster Salzburg  Salzburg Austria"},{"name":"AGMT  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u2010Artur","family":"Paiva","sequence":"additional","affiliation":[{"name":"Emergency and Intensive Care Department, Centro Hospitalar S\u00e3o Jo\u00e3o  Porto Portugal"},{"name":"Faculty of Medicine Universidade do Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Poissy","sequence":"additional","affiliation":[{"name":"Intensive Care Department Universit\u00e9 de Lille, Inserm U1285, CHU Lille, P\u00f4le de R\u00e9animation, CNRS, UMR 8576\u2013UGSF\u2013Unit\u00e9 de Glycobiologie Structurale et Fonctionnelle  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Peiffer\u2010Smadja","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"},{"name":"AP\u2010HP, H\u00f4pital Bichat, Service de Maladies Infectieuses et Tropicales  Paris France"},{"name":"National Institute for Health Research, Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Costagliola","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Inserm, Institut Pierre\u2010Louis d'\u00c9pid\u00e9miologie et de Sant\u00e9 Publique  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazdan","family":"Yazdanpanah","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"},{"name":"AP\u2010HP, H\u00f4pital Bichat, Service de Maladies Infectieuses et Tropicales  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maude","family":"Bouscambert\u2010Duchamp","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Institut des Agents Infectieux de Lyon Centre National de R\u00e9f\u00e9rence des Virus Respiratoires France Sud, Hospices Civils de Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Gagneux\u2010Brunon","sequence":"additional","affiliation":[{"name":"CHU de Saint\u2010Etienne, Service d'Infectiologie  Saint\u2010Etienne France"},{"name":"Universit\u00e9 Jean Monnet, Universit\u00e9 Claude Bernard Lyon 1, GIMAP, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon  Saint\u2010Etienne France"},{"name":"CIC 1408, INSERM  Saint\u2010Etienne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Ader","sequence":"additional","affiliation":[{"name":"D\u00e9partement des Maladies Infectieuses et Tropicales Hospices Civils de Lyon  Lyon France"},{"name":"D\u00e9partement des Maladies Infectieuses et Tropicales Universit\u00e9 Claude Bernard Lyon 1, CIRI, INSERM U1111, CNRS UMR5308, ENS Lyon  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7045-1275","authenticated-orcid":false,"given":"France","family":"Mentr\u00e9","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"},{"name":"D\u00e9partement d'\u00c9pid\u00e9miologie AP\u2010HP, H\u00f4pital Bichat, Biostatistique et Recherche Clinique  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3174-6246","authenticated-orcid":false,"given":"Florent","family":"Wallet","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Intensive R\u00e9animation Anesth\u00e9sie, Centre Hospitalier Lyon Sud Hospices Civils de Lyon  Pierre\u2010Benite France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Burdet","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"},{"name":"D\u00e9partement d'\u00c9pid\u00e9miologie AP\u2010HP, H\u00f4pital Bichat, Biostatistique et Recherche Clinique  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-5482","authenticated-orcid":false,"given":"J\u00e9r\u00e9mie","family":"Guedj","sequence":"additional","affiliation":[{"name":"IAME Universit\u00e9 Paris Cit\u00e9, IAME, Inserm, F\u201075018  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the DisCoVeRy study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30232-2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1443"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa851"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017962118"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00507-2"},{"key":"e_1_2_11_7_1","unstructured":"Royal College of Physicians (London).National Early Warning Score (NEWS). Standardising the assessment of acute\u2010illness severity in the NHS. Report of a working party.2012."},{"key":"e_1_2_11_8_1","unstructured":"Royal College of Physicians.National Early Warning Score (NEWS) 2.Standardising the assessment of acute\u2010illness severity in the NHS. Updated report of a working party.2017."},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2012.12.016"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","unstructured":"World Health Organisation.Clinical management of severe acute respiratory infection when COVID\u201019 is suspected.Interim Guidance.2020https:\/\/www.who.int\/publications\u2010detail\/clinical\u2010management\u2010of\u2010severe\u2010acute\u2010respiratory\u2010infection\u2010when\u2010novel\u2010coronavirus\u2010(ncov)\u2010infection\u2010is\u2010suspected","DOI":"10.15557\/PiMR.2020.0003"},{"key":"e_1_2_11_11_1","unstructured":"National Institute for Health and Care Excellence (NICE).COVID\u201019 rapid guideline: managing suspected or confirmed pneumonia in adults in the community.2020https:\/\/www.nice.org.uk\/guidance\/ng165"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-041437"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(22)00295-X"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac048"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/emermed-2020-210624"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12543"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111477118"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m1985"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93828-y"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06536-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26601"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.0202"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035002"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12784"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021642118"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T18:59:34Z","timestamp":1704049174000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,11]]},"references-count":24,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1002\/psp4.13051"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13051","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,11]]},"assertion":[{"value":"2023-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}