Clinical antiviral efficacy of remdesivir and casirivimab/imdevimab against the SARS-CoV-2 Delta and Omicron variants
Author:
Jittamala Podjanee, Schilling William HK, Watson James A, Luvira Viravarn, Siripoon Tanaya, Ngamprasertchai Thundon, Almeida Pedro J, Ekkapongpisit Maneerat, Cruz Cintia, Callery James J, Boyd Simon, Anunsittichai Orawan, Hongsuwan Maliwan, Singhaboot Yutatirat, Pagornrat Watcharee, Tuntipaiboontana Runch, Kruabkontho Varaporn, Ngernseng Thatsanun, Tubprasert Jaruwan, Abdad Mohammad Yazid, Keayarsa Srisuda, Madmanee Wanassanan, Aguiar Renato S, Santos Franciele M, Batty Elizabeth MORCID, Hanboonkunupakarn Pongtorn, Hanboonkunupakarn Borimas, Sookprome Sakol, Poovorawan Kittiyod, Imwong Mallika, Taylor Walter RJ, Chotivanich Vasin, Sangketchon Chunlanee, Ruksakul Wiroj, Chotivanich Kesinee, Pukrittayakamee Sasithon, Dondorp Arjen M, Day Nicholas PJ, Teixeira Mauro M, Piyaphanee Watcharapong, Phumratanaprapin Weerapong, White Nicholas J
Abstract
BackgroundUncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines. Early in the pandemic the monoclonal antibody cocktail, casirivimab/imdevimab, proved highly effective in clinical trials but because of weak or absentin vitroactivity against the SARS-CoV-2 Omicron BA.1 subvariant, it is no longer recommended.MethodsIn a multicenter open label, randomized, controlled adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days), casirivimab/imdevimab (600mg/600mg), and no study drug. The primary outcome was the viral clearance rate in the modified intention-to-treat population derived from daily log10viral densities (days 0-7) in standardized duplicate oropharyngeal swab eluates. This ongoing adaptive trial is registered atClinicalTrials.gov(NCT05041907).ResultsAcceleration in mean estimated SARS-CoV-2 viral clearance, compared with the contemporaneous no study drug arm (n=64), was 42% (95%CI 18 to 73%) for remdesivir (n=67). Acceleration with casirivimab/imdevimab was 58% (95%CI: 10 to 120) in Delta (n=13), and 20% (95%CI: 3 to 43) in Omicron variant (n=61) infections compared with contemporaneous no study drug arm (n=84). In apost hocsubgroup analysis viral clearance was accelerated by 8% in BA.1 (95%CI: −21 to 59) and 23% (95%CI: 3 to 49) in BA.2 and BA.5 Omicron subvariants.ConclusionsParenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Despite substantially reducedin vitroactivities, casirivimab/imdevimab retainsin vivoantiviral activity against COVID-19 infections caused by currently prevalent Omicron subvariants.Brief summaryIn early symptomatic COVID-19 remdesivir accelerated viral clearance by 42% while the monoclonal antibody cocktail casirivimab/imdevimab accelerated clearance by approximately 60% in SARS-CoV-2 Delta variant infections, and by approximately 25% in infections with Omicron subvariants BA.2 and BA.5.
Publisher
Cold Spring Harbor Laboratory
Cited by
4 articles.
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