{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:10:44Z","timestamp":1789398644822,"version":"build-2803163510"},"reference-count":20,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-21-COVR-0022"],"award-info":[{"award-number":["ANR-21-COVR-0022"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The SARS-CoV-2 variant of concern, \u03b1, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations\/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged \u226518 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant \u03b1, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 \u00b1 11.9 vs. 60.5 \u00b1 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3\u20138] vs. 3 [2\u20134]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, \u03b1, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant \u03b1, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.<\/jats:p>","DOI":"10.3390\/v14071529","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:12:40Z","timestamp":1657757560000},"page":"1529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["SARS-CoV-2 Genomic Characteristics and Clinical Impact of SARS-CoV-2 Viral Diversity in Critically Ill COVID-19 Patients: A Prospective Multicenter Cohort Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-5467","authenticated-orcid":false,"given":"Slim","family":"Fourati","sequence":"first","affiliation":[{"name":"Department of Virology, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"},{"name":"Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"},{"name":"INSERM U955, Team \u00abViruses, Hepatology, Cancer\u00bb, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etienne","family":"Audureau","sequence":"additional","affiliation":[{"name":"INSERM U955 Team CEpiA, University Paris-Est-Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"Department of Public Health, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-5368","authenticated-orcid":false,"given":"Romain","family":"Arrestier","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"},{"name":"Groupe de Recherche Clinique CARMAS, Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4438-5793","authenticated-orcid":false,"given":"St\u00e9phane","family":"Marot","sequence":"additional","affiliation":[{"name":"Department of Virology, Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9\u2013Salp\u00eatri\u00e8re, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique (IPLESP), Sorbonne Universit\u00e9, INSERM U1136, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Dubois","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Universitaire Saint-Antoine, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique, Sorbonne Universit\u00e9, INSERM, AP-HP, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Voiriot","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pital Tenon, Assistance Publique\u2014H\u00f4pitaux de Paris, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles-Edouard","family":"Luyt","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9\u2013Salp\u00eatri\u00e8re, INSERM UMRS_1166-iCAN, Institute of Cardiometabolism and Nutrition, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3745-9427","authenticated-orcid":false,"given":"Tomas","family":"Urbina","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital Saint-Antoine, Sorbonne Universit\u00e9, 75571 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Mayaux","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9\u2013Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6612-2030","authenticated-orcid":false,"given":"Anne-Marie","family":"Roque-Afonso","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Paul Brousse, Assistance Publique\u2014H\u00f4pitaux de Paris, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4373-0711","authenticated-orcid":false,"given":"T\u00e0i","family":"Pham","sequence":"additional","affiliation":[{"name":"Groupe de Recherche Clinique CARMAS, Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"},{"name":"Service de M\u00e9decine Intensive-R\u00e9animation, Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital de Bic\u00eatre, DMU 4 CORREVE Maladies du C\u0153ur et des Vaisseaux, FHU Sepsis, Groupe de Recherche Clinique CARMAS, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Equipe d\u2019Epid\u00e9miologie Respiratoire Int\u00e9grative, CESP, Universit\u00e9 Paris-Saclay, UVSQ, Univ. Paris-Sud, INSERM U1018, 94807 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luce","family":"Landraud","sequence":"additional","affiliation":[{"name":"Laboratoire de Microbiologie, H\u00f4pital Louis Mourier, Assistance Publique\u2014H\u00f4pitaux de Paris, 92700 Colombes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9279-5538","authenticated-orcid":false,"given":"Benoit","family":"Visseaux","sequence":"additional","affiliation":[{"name":"Service de Virologie, H\u00f4pital Bichat-Claude Bernard, Assistance Publique\u2014H\u00f4pitaux de Paris, Universit\u00e9 de Paris, IAME INSERM UMR 1137, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6103-6416","authenticated-orcid":false,"given":"Damien","family":"Roux","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Intensive R\u00e9animation, DMU ESPRIT, H\u00f4pital Louis Mourier, Assistance Publique\u2014H\u00f4pitaux de Paris, 92700 Colombes, France"},{"name":"Institut Necker-Enfants Malades (INEM), Department of Immunology, Infectiology and Hematology, INSERM U1151, CNRS UMR 8253, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Bellaiche","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anesth\u00e9sie R\u00e9animations Chirurgicales, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9228-0649","authenticated-orcid":false,"given":"Anne-Sophie","family":"L\u2019honneur","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Cochin, Assistance Publique\u2014H\u00f4pitaux de Paris, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakaria","family":"Ait Hamou","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pital Cochin, Assistance Publique\u2014H\u00f4pitaux de Paris, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9gol\u00e8ne","family":"Brichler","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Avicenne, Assistance Publique\u2014H\u00f4pitaux de Paris, 93000 Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Gaudry","sequence":"additional","affiliation":[{"name":"Service de R\u00e9animation, H\u00f4pital Avicenne, Assistance Publique\u2014H\u00f4pitaux de Paris, 93000 Bobigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maud","family":"Salmona","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital Saint-Louis, Universit\u00e9 de Paris, INSERM HIPI, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Clere-Jehl","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Azoulay","sequence":"additional","affiliation":[{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pital Saint-Louis, Assistance Publique\u2014H\u00f4pitaux de Paris, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Morand-Joubert","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, H\u00f4pital Universitaire Saint-Antoine, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique, Sorbonne Universit\u00e9, INSERM, AP-HP, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4808-8999","authenticated-orcid":false,"given":"Anne-Genevi\u00e8ve","family":"Marcelin","sequence":"additional","affiliation":[{"name":"Department of Virology, Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9\u2013Salp\u00eatri\u00e8re, Institut Pierre Louis d\u2019Epid\u00e9miologie et de Sant\u00e9 Publique (IPLESP), Sorbonne Universit\u00e9, INSERM U1136, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Chaix","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie, Assistance Publique\u2014H\u00f4pitaux de Paris, H\u00f4pital Saint-Louis, Universit\u00e9 de Paris, INSERM HIPI, 75010 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Descamps","sequence":"additional","affiliation":[{"name":"Service de Virologie, H\u00f4pital Bichat-Claude Bernard, Assistance Publique\u2014H\u00f4pitaux de Paris, Universit\u00e9 de Paris, IAME INSERM UMR 1137, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-5577","authenticated-orcid":false,"given":"Armand","family":"Mekontso Dessap","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"},{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"},{"name":"Groupe de Recherche Clinique CARMAS, Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-5006","authenticated-orcid":false,"given":"Christophe","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Virology, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"},{"name":"Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"},{"name":"INSERM U955, Team \u00abViruses, Hepatology, Cancer\u00bb, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Pawlotsky","sequence":"additional","affiliation":[{"name":"Department of Virology, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"},{"name":"Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"},{"name":"INSERM U955, Team \u00abViruses, Hepatology, Cancer\u00bb, 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4833-4320","authenticated-orcid":false,"given":"Nicolas","family":"de Prost","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"},{"name":"M\u00e9decine Intensive R\u00e9animation, H\u00f4pitaux Universitaires Henri Mondor, Assistance Publique\u2014H\u00f4pitaux de Paris, 94010 Cr\u00e9teil, France"},{"name":"Groupe de Recherche Clinique CARMAS, Universit\u00e9 Paris-Est-Cr\u00e9teil (UPEC), 94010 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5189","DOI":"10.1016\/j.cell.2021.09.003","article-title":"The Emergence and Ongoing Convergent Evolution of the SARS-CoV-2 N501Y Lineages","volume":"184","author":"Martin","year":"2021","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e262","DOI":"10.1017\/S0950268820002599","article-title":"ORF3a Mutation Associated with Higher Mortality Rate in SARS-CoV-2 Infection","volume":"148","author":"Majumdar","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0140-6736(20)31757-8","article-title":"Effects of a Major Deletion in the SARS-CoV-2 Genome on the Severity of Infection and the Inflammatory Response: An Observational Cohort Study","volume":"396","author":"Young","year":"2020","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106272","DOI":"10.1016\/j.ijantimicag.2020.106272","article-title":"Different Mutations in SARS-CoV-2 Associate with Severe and Mild Outcome","volume":"57","author":"Nagy","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103403","DOI":"10.1016\/j.ebiom.2021.103403","article-title":"Comparing Infectivity and Virulence of Emerging SARS-CoV-2 Variants in Syrian Hamsters","volume":"68","author":"Abdelnabi","year":"2021","journal-title":"eBioMedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/S1473-3099(21)00318-2","article-title":"Mortality and Critical Care Unit Admission Associated with the SARS-CoV-2 Lineage B.1.1.7 in England: An Observational Cohort Study","volume":"21","author":"Patone","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2100348","DOI":"10.2807\/1560-7917.ES.2021.26.16.2100348","article-title":"Characteristics of SARS-CoV-2 Variants of Concern B.1.1.7, B.1.351 or P.1: Data from Seven EU\/EEA Countries, Weeks 38\/2020 to 10\/2021","volume":"26","author":"Funk","year":"2021","journal-title":"Eurosurveillance"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-021-03426-1","article-title":"Increased Mortality in Community-Tested Cases of SARS-CoV-2 Lineage B.1.1.7","volume":"593","author":"Davies","year":"2021","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/S1473-3099(21)00356-X","article-title":"The SARS-CoV-2 B.1.1.7 Variant and Increased Clinical Severity-the Jury Is Out","volume":"21","author":"Giles","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/S1473-3099(21)00170-5","article-title":"Genomic Characteristics and Clinical Effect of the Emergent SARS-CoV-2 B.1.1.7 Lineage in London, UK: A Whole-Genome Sequencing and Hospital-Based Cohort Study","volume":"21","author":"Frampton","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_11","unstructured":"Grint, D.J., Wing, K., Houlihan, C., Gibbs, H.P., Evans, S.J.W., Williamson, E., McDonald, H.I., Bhaskaran, K., Evans, D., and Walker, A.J. (2021). Severity of SARS-CoV-2 Alpha Variant (B.1.1.7) in England. Clin. Infect. Dis., ciab754."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lee, H.K., Knabl, L., Knabl, L., Wieser, M., Mur, A., Zabernigg, A., Schumacher, J., Kaiser, N., Furth, P.A., and Hennighausen, L. (2021). Immune Transcriptomes from Hospitalized Patients Infected with the SARS-CoV-2 Variants B.1.1.7 and B.1.1.7 Carrying the E484K Escape Mutation. medRxiv.","DOI":"10.1101\/2021.05.27.21257952"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1503\/cmaj.050051","article-title":"A Global Clinical Measure of Fitness and Frailty in Elderly People","volume":"173","author":"Rockwood","year":"2005","journal-title":"CMAJ"},{"key":"ref_14","unstructured":"WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection (2020). A Minimal Common Outcome Measure Set for COVID-19 Clinical Research. Lancet Infect. Dis., 20, e192\u2013e197."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"The SOFA (Sepsis-Related Organ Failure Assessment) Score to Describe Organ Dysfunction\/Failure. On Behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1001\/jama.1993.03510240069035","article-title":"A New Simplified Acute Physiology Score (SAPS II) Based on a European\/North American Multicenter Study","volume":"270","author":"Lemeshow","year":"1993","journal-title":"JAMA"},{"key":"ref_17","unstructured":"ARDS Definition Task Force, Ranieri, V.M., Rubenfeld, G.D., Thompson, B.T., Ferguson, N.D., Caldwell, E., Fan, E., Camporota, L., and Slutsky, A.S. (2012). Acute Respiratory Distress Syndrome: The Berlin Definition. JAMA, 307, 2526\u20132533."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"753823","DOI":"10.3389\/fmicb.2021.753823","article-title":"Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated with Clinical Outcomes and Transmission","volume":"12","author":"Pang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","article-title":"Factors Associated with COVID-19-Related Death Using OpenSAFELY","volume":"584","author":"Williamson","year":"2020","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"RECOVERY Collaborative Group, Horby, P., Lim, W.S., Emberson, J.R., Mafham, M., Bell, J.L., Linsell, L., Staplin, N., Brightling, C., and Ustianowski, A. (2021). Dexamethasone in Hospitalized Patients with COVID-19. N. Engl. J. Med., 384, 693\u2013704.","DOI":"10.1056\/NEJMoa2021436"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/7\/1529\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:49:44Z","timestamp":1760140184000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/7\/1529"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,13]]},"references-count":20,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["v14071529"],"URL":"https:\/\/doi.org\/10.3390\/v14071529","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,13]]}}}