Early oral antiviral use in patients hospitalised with COVID-19

Zarębska-Michaluk, Dorota; Flisiak, Robert

doi:10.1016/s1473-3099(22)00522-9

Cited by 5 publications

(4 citation statements)

References 10 publications

(12 reference statements)

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“…A retrospective cohort study from the Hong Kong VOC omicron wave returned similar results 17 ; death rates were significantly reduced in recipients of either drug, patients experienced a lower risk of disease progression (paxlovid HR 0.57, molnupiravir HR 0.6), and the time to achieving a low viral burden after treatment start was significantly shortened (HR 1.38 for either drug). However, the study did not support a direct comparison of drug efficacy due to imbalances in baseline characteristics of the study groups such as patient comorbidities, age, and vaccine status 44 .…”

Section: Discussionmentioning

confidence: 89%

Paxlovid-like nirmatrelvir/ritonavir fails to block SARS-CoV-2 transmission in ferrets

Cox

Lieber

Wolf

et al. 2022

Preprint

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Despite the continued spread of SARS-CoV-2 and emergence of variants of concern (VOC) that are capable of escaping preexisting immunity, therapeutic options are underutilized. In addition to preventing severe disease in high-risk patients, antivirals may contribute to interrupting transmission chains. The FDA has granted emergency use authorizations for two oral drugs, molnupiravir and paxlovid. Initial clinical trials suggested an efficacy advantage of paxlovid, giving it a standard-of-care-like status in the United States. However, recent retrospective clinical studies suggested a more comparable efficacy of both drugs in preventing complicated disease and case-fatalities in older adults. For a direct efficacy comparison under controlled conditions, we assessed potency of both drugs against SARS-CoV-2 in two relevant animal models; the Roborovski dwarf hamster model for severe COVID-19 in high-risk patients and the ferret model of upper respiratory tract disease and transmission. After infection of dwarf hamsters with VOC omicron, paxlovid and molnupiravir were efficacious in mitigating severe disease and preventing death. However, a pharmacokinetics-confirmed human equivalent dose of paxlovid did not significantly reduce shed SARS-CoV-2 titers in ferrets and failed to block virus transmission to untreated direct-contact ferrets, whereas transmission was fully suppressed in a group of animals treated with a human-equivalent dose of molnupiravir. Prophylactic administration of molnupiravir to uninfected ferrets in direct contact with infected animals blocked productive SARS-CoV-2 transmission, whereas all contacts treated with prophylactic paxlovid became infected. These data confirm retrospective reports of similar therapeutic benefit of both drugs for older adults, and reveal that treatment with molnupiravir, but not paxlovid, may be suitable to reduce the risk of SARS-CoV-2 transmission.

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Section: Discussionmentioning

confidence: 89%

Paxlovid-like nirmatrelvir/ritonavir fails to block SARS-CoV-2 transmission in ferrets

Cox

Lieber

Wolf

et al. 2022

Preprint

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“…The retrospective analyses of members of Clalit Health Services 16,19 and a retrospective cohort study from the Hong Kong VOC omicron wave 17 demonstrated that both paxlovid 16 and molnupiravir 19 significantly lowered the risk of progression to severe disease and deaths in older adults. However, a direct comparison of drug efficacy was not possible due to imbalances in baseline characteristics of the study groups such as patient comorbidities, age, and vaccine status 46 . To assess efficacy of both drugs against COVID-19 of different severity under equivalent experimental conditions, we employed the Roborovski dwarf hamster and ferret models of SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models

Cox,

Lieber,

Wolf

et al. 2023

Nat Commun

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Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults. Here, we compare both drugs in two animal models; the Roborovski dwarf hamster model for severe COVID-19-like lung infection and the ferret SARS-CoV-2 transmission model. Dwarf hamsters treated with either drug survive VOC omicron infection with equivalent lung titer reduction. Viral RNA copies in the upper respiratory tract of female ferrets receiving 1.25 mg/kg molnupiravir twice-daily are not significantly reduced, but infectious titers are lowered by >2 log orders and direct-contact transmission is stopped. Female ferrets dosed with 20 or 100 mg/kg nirmatrelvir/ritonavir twice-daily show 1–2 log order reduction of viral RNA copies and infectious titers, which correlates with low nirmatrelvir exposure in nasal turbinates. Virus replication resurges towards nirmatrelvir/ritonavir treatment end and virus transmits efficiently (20 mg/kg group) or partially (100 mg/kg group). Prophylactic treatment with 20 mg/kg nirmatrelvir/ritonavir does not prevent spread from infected ferrets, but prophylactic 5 mg/kg molnupiravir or 100 mg/kg nirmatrelvir/ritonavir block productive transmission. These data confirm reports of similar efficacy in older adults and inform on possible epidemiologic benefit of antiviral treatment.

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“…The pharmacological characteristics, mechanism of action and clinical use of these drugs have been reviewed previously [9 & ]. These randomized trials were performed when delta and earlier variants were circulating, and involved unvaccinated individuals and relatively small proportions of older adults [10]. It was thus uncertain whether similar efficacy would be observed in vaccinated (with and without boosters) individuals who are older and had a wider spectrum of comorbidities, or affected by the omicron variant, which had a 60-70% lower risk of hospitalization and death than the delta variant [11].…”

Section: Treatment Of Mild-to-moderate Covid-19 Disease In the Outpat...mentioning

confidence: 99%

Drug treatment of COVID-19 infection

Lui

Guaraldi

2023

Current Opinion in Pulmonary Medicine

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Purpose of reviewCOVID-19 pandemic has caused more than 6.6 million deaths globally. Tremendous efforts have been committed for the development of new and repurposed drugs for the treatment of COVID-19. Although different international and national guidelines share consensus in the management of COVID-19 disease with different levels of severity, new challenges have emerged, steering the need for ongoing research in advancing the clinical management of COVID-19.Recent findingsThis review focuses on recent data from randomized trials and postmarketing real-world evidence for the treatment of mild to moderate disease in the outpatient setting and patients hospitalized for COVID-19 with varying level of severity. Relevant data for treatment of the latest omicron sub-variants in people who received vaccination are presented. Challenges in special populations, including immunocompromised hosts, patients with renal failure and pregnant women, are also discussed.SummaryTreatment of COVID-19 should be personalized according to host characteristics, degree of severity and available treatment options.

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Early oral antiviral use in patients hospitalised with COVID-19

Cited by 5 publications

References 10 publications

Paxlovid-like nirmatrelvir/ritonavir fails to block SARS-CoV-2 transmission in ferrets

Paxlovid-like nirmatrelvir/ritonavir fails to block SARS-CoV-2 transmission in ferrets

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models

Drug treatment of COVID-19 infection

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