Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study

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"10.1016/S1473-3099(24)00353-0_bib27", "volume": "24", "year": "2023" }, { "DOI": "10.1128/AAC.00602-21", "article-title": "Key metabolic enzymes involved in remdesivir activation in human lung cells", "author": "Li", "doi-asserted-by": "crossref", "journal-title": "Antimicrob Agents Chemother", "key": "10.1016/S1473-3099(24)00353-0_bib28", "volume": "65", "year": "2021" }, { "DOI": "10.4049/jimmunol.1600055", "article-title": "HIV protease inhibitor-induced cathepsin modulation alters antigen processing and cross-presentation", "author": "Kourjian", "doi-asserted-by": "crossref", "first-page": "3595", "journal-title": "J Immunol", "key": "10.1016/S1473-3099(24)00353-0_bib29", "volume": "196", "year": "2016" }, { "DOI": "10.1016/j.antiviral.2022.105430", "article-title": "Combination therapy with nirmatrelvir and molnupiravir improves the survival of SARS-CoV-2 infected mice", "author": "Jeong", "doi-asserted-by": "crossref", "journal-title": "Antiviral Res", "key": "10.1016/S1473-3099(24)00353-0_bib30", "volume": "208", "year": "2022" }, { "DOI": "10.1038/s42003-022-03101-9", "article-title": "Combination of antiviral drugs inhibits SARS-CoV-2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "154", "journal-title": "Commun Biol", "key": "10.1016/S1473-3099(24)00353-0_bib31", "volume": "5", "year": "2022" }, { "article-title": "Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomised controlled study", "author": "Liu", "first-page": "1", "journal-title": "Lancet Reg Health West Pac", "key": "10.1016/S1473-3099(24)00353-0_bib32", "volume": "33", "year": "2023" }, { "DOI": "10.1093/cid/ciad371", "article-title": "Safety profile and clinical and virological outcomes of nirmatrelvir–ritonavir treatment in patients with advanced chronic kidney disease and coronavirus disease 2019", 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